Nutrition and HIV/AIDS: nutritional guidelines for HIV-infected adults and children in Southern Africa: meeting the needs (Sections 3-6).
3.1 PROVIDING NUTRITION, PROVIDING FOOD
To maintain or achieve good health, each person requires energy-providing nutrients (protein, fat and carbohydrates), vitamins, minerals and water. The average minimum daily energy requirement of an adult in the developing world is 2 100 kcal. This is sufficient only for those in good health who are engaged in light physical activity at an ambient temperature of 20[degrees]C. (1) Most of this energy comes from carbohydrate. Under normal circumstances protein should comprise 10-12% of daily energy, and fat a further 17%. (1,2) However, protein comprises a very small part of the average diet of children in Africa and Asia. Hence these children are vulnerable to protein depletion. The World Health Organization (WHO) recommends that energy intake in asymptomatic HIV-infected adults and children be increased by 10%. During periods of illness or convalescence this should be increased to 20-30%. (3) Where possible, this increased energy requirement should be given as food. Where weight loss and malnutrition are severe, the energy needs of HIV-infected children may increase by 100%. (4) Overweight but asymptomatic patients need to be encouraged to lose excess weight, eat a balanced diet and exercise regularly. An improvement in nutrition of the malnourished may enhance immune function, prevent weight loss--particularly the loss of lean mass--and possibly delay disease progression. (5) Exclusive breastfeeding of the infants of HIV-infected mothers has reduced the risk of transmission compared with mixed feeding, and has promoted the survival of such children. (6,7)
3.2 THERAPEUTIC FEEDING
Therapeutic feeding provides the total nutritional needs of a severely malnourished person in the form of a specifically prepared and formulated diet. F100 has been the WHO's standard therapeutic feed and provides severely malnourished children with 150-220 kcal/kg/day. (1) A recent addition is the 'ready-to-use therapeutic feed' (RUTF), a mix based on peanut butter, skimmed milk, oil, sugar and micronutrients in a sterile carton that does not require reconstitution with water and therefore avoids potential bacterial contamination. Therapeutic feeds are usually continued for a minimum of 4-6 weeks or until the present nutritional crisis is past. These special feeds are often used in famine or warfare situations where acute malnutrition is frequent. South African hospitals and clinics use alternative nutrient supplements.
3.3 FAMILY FOOD SUPPORT
What ought to be done when a patient or family has insufficient food at home? At each clinic visit questions must be asked that check food security, access to food and the quality and quantity of that food. How is it prepared, and who ensures that the child or sick adult is fed? Is assistance needed? Clinic staff can help in the following ways:
* Supplementary feeds are available from government institutions as well as some NGOs. Social workers will assist with accessing financial grants, etc. Those families who can be helped with growing their own vegetables must be referred to local agencies that provide such support.
* The National Strategic Plan provides for food parcels to be available from government clinics.
* Exclusive breastfeeding programmes should be promoted and protected where mothers are unable to provide reliable or safer alternatives to infant feeding. Mothers who are exclusively breastfeeding should be encouraged to continue ART through this period and an attempt should be made to ensure that the maternal viral load is kept well controlled, i.e. by measurement of the mother's viral load at least once during the breastfeeding period.
* Children from 6 months to 5 years ought to receive supplemental vitamin A every 6 months. See below.
* Children experiencing diarrhoea should be given zinc supplementation over this period. See below.
* Lobby government and industry to ensure that staple foods are fortified with appropriate micronutrients: iodised salt, fortified flour and cereals. Take a detailed history from the patient and assess the 'quality' of the food being consumed. Teamwork on the part of the health worker is essential, and where practical, the health worker is encouraged to upgrade his/her skill and knowledge with educational courses in the field. Identify and involve community members or agencies that can provide food, educate the community with regard to nutrition, and promote skills needed in the home production and preparation of food.
3.4 NUTRITION IN THE RELIEF OF HIV-RELATED SYMPTOMS
If symptoms persist for more than a week or are unresponsive to simple home-based care, the child or adult who is HIV positive must be referred to a health practitioner (nurse or doctor) or a clinic or hospital where a diagnosis can be made and corrective treatment instituted (Table 3.I). If the patient is very ill, refer him/her to a doctor immediately. Untreated diseases of the mouth and persistent diarrhoea commonly lead to a loss of appetite and weight loss. (8)
3.5 NUTRITIONAL SUPPLEMENTS: VITAMINS AND OTHER MICRONUTRIENTS
Vitamins and minerals are, by definition, essential for life. Do they influence the progression of HIV infection? Micronutrient studies in HIV-infected subjects have been difficult to interpret: the studies differ in the composition and quantities of micronutrients, and few have been randomised and adequately controlled, while in many the effect of the acute-phase response and the effect of the simultaneous intake of micronutrients in food (dietary micronutrients) is seldom taken into account. Nor have the potential interactions between the micronutrients themselves--particularly within the multivitamin cocktail--been assessed in vivo. (10) Data from North American and European studies are not immediately applicable to Africa. The staging of HIV is missing from many studies, and the confounding effect of opportunistic disease in subjects is not regularly discussed. Although pre-ARV treatment hospital-based studies from the developed world reported low baseline micronutrient levels in their subjects, selection bias, unknown recruitment criteria and the absence of disease stage have limited the interpretation of these data. (11)
3.5.2 Individual vitamins and micronutrients (Tables 3.II and 3.III) (10)
Vitamin A (retinol, retinoic acid, [beta]-carotene)
Adults: Supplementation of HIV-infected adults with vitamin A is likely to be safe provided dosing does not exceed the daily recommended dietary allowance (RDA), and in cases where deficiency is confirmed (4,12) (see comment and RDA dosing below).
Children: Current evidence supports the use of vitamin A supplementation in under-5-year-olds in Africa and Asia. Supplementation reduces the risk of diarrhoea-related morbidity and mortality and 'all-risk' mortality in HIV-infected and uninfected children. (13-16) Children are supplemented with 50 000 IU of vitamin A at 1 and 3 months, 100 000 IU at 6 and 9 months and 200 000 IU at 12 and 15 months. Further supplementation with 200 000 IU 6-monthly thereafter until the age of 5 years is recommended. (12,13)
Comment: Observational studies in Africa have reported low maternal serum vitamin A levels in pregnant women who also appear to be at an increased risk of perinatal transmission of HIV. Kenyan studies found that low maternal serum retinol predicted increased virus in breastmilk and increased genital shedding of HIV. (10) Vitamin A supplementation of HIV-infected pregnant women has been associated with an increase in birth weight and fewer preterm births. (17) But the perinatal transmission studies have failed to demonstrate any reduction in viral transmission. (18,19) Indeed, a Tanzanian trial of vitamin A supplementation not only failed to show benefit above placebo but reported an increase in viral transmission in breastfeeding mothers. (18,20) Tang et al. speculate that vitamin A supplementation promotes cellular differentiation leading to the increased expression of CCR5 co-receptors on CD4 cells, thereby aiding viral entry. (11,21) Retinol levels decrease during the acute-phase response--i.e. low serum levels of vitamin A do not necessarily imply nutritional deficiency. (10,11)
Recommended dietary allowances (RDA) for vitamin A ([micro]g/d) in HIV-uninfected populations (22) (recommendations are expected to apply equally to HIV-infected persons):
Infants 0-6 mo. = 400, 7-12 mo. = 500; children 1-3 yrs = 300, 4-8 yrs = 400; males 9-13 yrs = 600, 14->70 yrs = 900; females 9-13 yrs = 600, 14->70 yrs = 700; pregnancy [less than or equal to] 18 yrs = 750, 19 - 50 yrs = 770; lactation [less than or equal to] 18 yrs = 1 200, 19 - 50 yrs = 1 300.
Vitamin B group
Adults and children: There are no randomised controlled trials (RCTs) that examine the separate contribution of the individual B-group vitamins to the wellbeing or transmission risk of HIV-infected persons. Supplementation with 1 x RDA is currently recommended until additional data are available. (10,12)
Comment: RCTs in Tanzania and Thailand have shown benefit with multivitamin supplements that have included the following B-group vitamins: thiamine, riboflavin, pyridoxine and vitamin [B.sub.12]. (20,23) The Tanzanian trials noted improved birth outcomes among pregnant HIV-positive women given multivitamin supplements. In particular, CD4+ and CD8+ levels improved and subjects progressed less rapidly to advanced HIV disease and were less likely to die. The design, methodology and the use of extremely high doses of micronutrients in these trials has, however, been questioned. (4,10) Nevertheless, some observational studies have also recorded benefit with vitamin B supplementation including a reduced risk of HIV progression. (10) Benefit in the Thailand RCT was limited to those with CD4 levels below 100 cells/[micro]l. A small placebo-controlled prospective USA-based study of multi-micronutrient supplementation--including high doses of many of the B-group vitamins--reported improved CD4 counts after 12 weeks in patients on ARVs. (24) Tang et al.'s comment may have relevance: '[while] a combination of vitamins may provide some benefit to undernourished HIV-infected subjects with advanced disease, the role of individual nutrients is less clear'. (11)
RDA daily intakes for the B-group vitamins: (22)
Thiamine (vitamin [B.sub.1], mg/d): Infants 0-6 mo. = 0.2 , 7-12 mo. = 0.3; children 1-3 yrs = 0.5, 4-8 yrs = 0.6; males 9-13 yrs = 0.9, 14->70 yrs = 1.2; females 9-13 yrs = 0.9, 14-18 yrs = 1.0, 19->70 yrs = 1.1; pregnancy and lactation [less than or equal to] 18 - 50 yrs = 1.4.
Riboflavin (vitamin [B.sub.2], mg/d): Infants 0-6 mo. = 0.3, 7-12 mo. = 0.4; children 1-3 yrs = 0.5, 4-8 yrs = 0.6; males 9-13 yrs = 0.9, 14->70 yrs = 1.3; females 9-13 yrs = 0.9, 14-18 yrs = 1.0, 19->70 yrs = 1.1; pregnancy = 1.4; lactation = 1.6.
Niacin (vitamin [B.sub.3], mg/d): Infants 0-6 mo.= 2, 7-12 mo. = 4; children 1-3 yrs = 6, 4-8 yrs = 8; males 9-13 yrs = 12, 14->70 yrs = 16; females 9-13 yrs = 12, 14- >70 yrs = 14; pregnancy = 18; lactation = 17.
Pyridoxine (vitamin B6, mg/d): Infants 0-6 mo. = 0.1, 7-12 mo. 0.3; children 1-3 yrs = 0.5, 4-8 yrs = 0.6; males 9 -13 yrs = 1.0, 14-50 yrs = 1.3, 51->70 yrs = 1.7; females 9-13 yrs = 1.0, 14-18 yrs = 1.2, 19-50 yrs = 1.3, 51->70 yrs = 1.5; pregnancy [less than or equal to] 18 yrs = 1.6, 19-50 yrs = 1.9; lactation = 2.0.
Folate ([micro]g/d): Infants 0-6 mo. = 65, 7 - 12 mo. = 80; children 1-3 yrs = 150, 4-8 yrs = 200; males 9-13 yrs = 300, 14->70 yrs = 400; females 9-13 yrs = 300, 14->70 yrs = 400; pregnancy = 600; lactation = 500.
Vitamin [B.sub.12]: Infants 0-6 mo. = 0.4, 7-12 mo. = 0.5; children 1-3 yrs = 0.9, 4-8 yrs = 1.2; males 9-13 yrs = 1.8, 14->70 yrs = 2.4; females 9-13 yrs = 1.8, 14->70 yrs = 2.4; pregnancy = 2.6; lactation = 2.8.
Adults and children: RCT data detailing a specific role for vitamin C are absent apart from multivitamin studies that have included vitamin C together with other micronutrients. Where supplementation is indicated because of malnutrition or where patients wish to take vitamin supplements, it is recommended that doses of 1 x daily RDA be taken. (10,12)
Comment: Vitamin C supplementation formed part of the multivitamin RCTs in Tanzania and Thailand discussed above. (20,23) Observational studies have suggested that vitamin C may reduce HIV progression. (10) Further data suggest that vitamin C may behave as an antioxidant in HIV-positive subjects, though the clinical value of this is unknown. Baseline levels of vitamin C have been reported to be low in some studies of HIV-infected patients, including children. (25,26)
RDA daily intake for vitamin C (mg/d): (22)
Infants 0-6 mo. = 40, 7-12 mo. = 50; children 1-3 yrs = 15, 4-8 yrs = 25; males 9-13 yrs = 45, 14-18 yrs = 75, 19->70 yrs = 90; females 9-13 yrs = 45, 14-18 yrs = 65, 19->70 yrs = 75; pregnancy [less than or equal to] 18 yrs = 80, 19-50 yrs = 85; lactation [less than or equal to] 8 yrs = 115, 19-50 yrs = 120.
Adults and children: Currently there are no data directly assessing the role of vitamin D supplementation in HIV-infected adults and children. However, standard recommendations apply to pregnant women, infants including exclusively breastfed infants, and older children. Where osteoporosis is present, vitamin D 200 IU daily for adults aged <50 years, 400 IU daily for those aged 51-70 years and 600 IU daily for those aged [greater than or equal to] 71 years is recommended for the general population. (27)
Comment: Bone loss is a frequent complication of HIV infection and may accompany ARV treatment. Both adults and children are at risk. A preventive role for vitamin D and calcium is not yet established. (28) Despite plenty of sunshine, rickets remains a problem in developing countries where the diet may be low in vitamin D or where children are kept indoors. There is little vitamin D in human milk. Sunlight and supplementation of exclusively breastfed infants (irrespective of HIV status) is recommended. (29) An association between vitamin D and the activation of Toll-like receptors on macrophages infected with Mycobacterium tuberculosis has been noted. However, there are currently no data to suggest that vitamin D supplementation of dual HIV/TB-infected patients should be recommended. (30)
RDA for vitamin D ([micro]g/d): (22)
Infants, children and adults 0 mo.-50 yrs = 5; adults 51 -70 yrs = 10, >70 yrs = 15; pregnancy and lactation = 5.
Vitamin E, [alpha]-tocopherol
Adults and children: Daily supplementation with not more than 1 x RDA is acceptable.
Comment: The North American Multicenter AIDS Cohort Study (MACS) found a reduced risk of progression to AIDS or death during 9 years of follow-up in those subjects with high levels of vitamin E, but whether this is an acute-phase epiphenomenon, a reflection of the stage of infection or a direct effect of vitamin E remains uncertain. (10) Vitamin E is a major lipid-soluble antioxidant in cell membranes, where it functions as a scavenger of free radicals. It interacts with several other antioxidants and micronutrients--zinc, selenium, copper and vitamin C--and its activity is dependent upon sufficient levels of these other nutrients within the cell. (11) It is suggested that daily requirements of vitamin E ought to be increased during the simultaneous use of the pro-oxidant, iron. (10) There are no RCTs using vitamin E alone in HIV-positive patients, although both the Tanzanian and Thailand studies of multivitamin supplementation contained vitamin E in large doses. (20,23)
RDA of vitamin E (mg/d, [alpha]-tocopherol): (22)
Infants 0-6 mo. = 4, 7-12 mo. = 5; children 1-3 yrs = 6, 4-8 yrs = 7; males 9-13 yrs = 11, 14->70 yrs = 15; females 9-13 yrs = 11, 14->70 yrs = 15; pregnancy = 15; lactation = 19.
Adults and children: There is no evidence that iron supplementation is required for HIV-infected patients apart from periods of increased physiological need such as pregnancy and periods of identified iron deficiency.
Comment: High iron stores (increased serum ferritin levels and increased marrow iron) have been associated with shortened survival of HIV-positive patients. This relationship probably reflects advanced HIV disease itself, so-called reverse causality: serum levels of ferritin increase during the acute-phase response and thus mark advancing disease. (10) Anaemia in the setting of HIV infection is not invariably associated with iron deficiency and iron studies must be checked before supplementing with iron. Iron supplementation trials in non-HIV-infected children in developing regions caution against the generalised provision of iron to children where infectious diseases such as malaria and TB are rife. Mortality may be enhanced. (31,10)
RDA of iron (mg/d) (22)
Infants 0-6 mo. = 0.27, 7-12 mo. = 11; children 1-3 yrs = 7, 4-8 yrs = 10; males 9-13 yrs = 8, 14-18 yrs = 11, 19 ->70 yrs = 8; females 9-13 yrs = 8, 14-18 yrs = 15, 19 -50 yrs = 18, 51->70 yrs = 8; pregnancy = 27; lactation [less than or equal to] 18 yrs = 10, 19-50 yrs = 9.
Adults and children: There are no definitive data to guide the HIV clinician or treater. Daily supplementation with not more than 1 x RDA is prudent.
Comments: A study from Kenya indicated that low selenium levels were a predictor of vaginal HIV shedding, and in prospective cohort studies in both developed and developing countries, low selenium levels have been associated with an increased risk of death. Unfortunately these studies failed to exclude confounding from an acute-phase response. Tanzanian pregnancy data linking low selenium to increased HIV mortality falter for the same reasons. (10) Nevertheless, selenium is a major constituent of glutathione peroxidase, an important cellular antioxidant, and is believed to guard against damage to proteins, lipids, lipoproteins and DNA itself. (32) A recent report from North America indicated improvement in viral load and CD4 levels in an intention-to-treat RCT involving 450 subjects. High doses of selenium, 200 [micro]g/d, were used, and only 174 patients completed the 9-month follow-up. (33) Clearly more data from African studies are needed.
RDA of selenium ([micro]g/d): (22)
Infants 0-6 mo. = 15, 7-12 mo. = 20; children 1-3 yrs = 20, 4-8 yrs = 30; males 9-13 yrs = 40, 14->70 yrs = 55; females 9-13 yrs = 40, 14->70 yrs = 55; pregnancy = 60; lactation = 70.
Adults: There is currently insufficient evidence to recommend zinc supplementation of all HIV-infected adults. If daily supplementation is considered, it is advised that standard 1 x RDA doses are used.
Children: Zinc supplementation during episodes of chronic diarrhoea is recommended: a daily dose of 10 mg zinc for 2 weeks in HIV-positive children under 5 years. (4,12) A daily supplement dose of 3 mg zinc for 6 months has also been shown to be safe in this age group. (12)
Comment: Zinc supplementation of children in developing regions is associated with fewer episodes of watery diarrhoea and a reduced mortality from both diarrhoea and pneumonia. This applies to both HIV-infected and uninfected children. (34,35) The provision of zinc to children with diarrhoea has been helpful: see doses below (box, p. 41). USA studies found baseline levels of copper to be higher and zinc lower in HIV-infected subjects with progressive disease, but toenail concentrations and levels of dietary intake of these trace elements were actually the same in both subjects and controls. The alterations in the serum levels probably reflect advancing HIV infection. Serum zinc levels fall in response to the acute-phase phenomenon. (10) HIV requires zinc in its structural proteins and its enzymic activity: 'zinc-fingers' are part of the reverse transcriptase enzyme. Excessive zinc intake may be harmful. At least one American study found zinc intake to be associated with more rapid progression to AIDS and death. (10) Furthermore, large doses of zinc have also been found to be immunosuppressive. (36)
RDA of zinc (mg/d): (22)
Infants 0-6 mo. = 2, 7-12 mo. = 3; children 1-3 yrs = 3, 4 -8 yrs = 5; males 9-13 yrs = 8, 14->70 yrs = 11; females 9-13 yrs = 8, 14-18 yrs = 9, 19->70 yrs = 8; pregnancy [less than or equal to] 18 yrs = 12, 19-50 yrs = 11; lactation [less than or equal to] 18 yrs = 13, 19 -50 yrs = 12.
Adults and children: There are no data specific to the HIV-infected population. Standard recommendations apply.
Comment: A low calcium intake has been described in South African schoolchildren. (37-39) During the 1999 National Food Consumption Survey, 21.6% of 1-9-year-olds were found to have stunted growth. The diet of these children was noted to be broadly deficient in many nutrients. (40) While many HIV-infected adults and children demonstrate reduced bone mineral density, a role for calcium deficiency and the value of its replacement needs further study in African HIV-positive populations. Osteopenia and osteoporosis in patients with HIV is multifactorial in cause and frequently associated with underlying disease progression or to the therapy employed in viral control.
RDA for calcium (mg/d): (22)
Infants 0-6 mo. = 210, 7-12 mo. = 270; 1-3 yrs = 500, 4 - 8 yrs = 800; males 9-18 yrs = 1 300, 19-50 yrs = 1 000, 51->70 yrs = 1 200; females 9-18 yrs = 1 300, 19 -50 yrs = 1 000, 51->70 yrs = 1 200; pregnancy [less than or equal to] 18 yrs = 1 300, 19-50 yrs = 1 000; lactation [less than or equal to] 18 yrs = 1 300, 19 -50 yrs = 1 000.
A recent Cochrane review of 15 micronutrient trials in HIV-infected subjects noted no effect of vitamin A or [beta]-carotene on mortality, morbidity or viral load or CD4 cell levels. The authors remark that 'there is no conclusive evidence at present to show that micronutrient supplementation effectively reduces mortality and morbidity among HIV-infected adults though there is evidence of benefit of vitamin A supplementation in children'. (41) These authors agree that it is reasonable to support the WHO's recommendations to promote the adequate dietary intake of micronutrients at RDA levels and to provide vitamin A supplementation to children.
Many HIV-infected patients are poor and unemployed and malnutrition is common, particularly among children. The national strategic plan provides for the supplementation of those in need. The HIV-infected must be identified and offered assistance before malnutrition becomes overt. Randomised controlled micronutrient studies are needed in the HIV-infected of southern Africa. Currently huge gaps in knowledge remain. Adequate nutrition must be provided together with ARVs. Controlling the virus without providing food and micronutrients will not restore weight or correct metabolic and cellular function in the malnourished.
(1.) Young H, Borrel A, Holland D, Salama P. Public nutrition in complex emergencies. Lancet 2004; 364: 1899-1909.
(2.) United Nations High Commissioner for Refugees, United Nations Children's Fund, World Food Programme, World Health Organisation. Food and Nutrition Needs in Emergencies. Geneva: UNHCR, UNICEF, WFP, WHO, 2002.
(3.) Hsu JW-C, Pencharz PB, Macallan D, Tomkins A. Macronutrients and HIV/AIDS: a review of current evidence. World Health Organization, 2005. Consultation on Nutrition and HIV/AIDS in Africa. Evidence, lessons and recommendations for action. Durban, South Africa, 10-13 April 2005.
(4.) Executive summary of a Scientific Review. World Health Organisation, 2005. Consultation on Nutrition and HIV/AIDS in Africa: Evidence, lessons and recommendations for action. Durban, South Africa, 10-13 April 2005.
(5.) Piwoz EG, Elizabeth A. HIV/AIDS and Nutrition. A review of the literature and recommendations for nutritional care and support in sub-Saharan Africa. Washington, DC: Academy for Educational Development (AED), 2000.
(6.) Coovadia HM, Rollins NC, Bland RM, et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 2007; 369: 1107-1116.
(7.) World Health Organization. WHO HIV and Infant Feeding Technical Consultation held on behalf of the Interagency Task Team (IATT) on Prevention of HIV Infections in Pregnant Women, Mothers and their Infants. Geneva, 25-27 October 2006. http://www.int/child-adolescent-health/NUTRITION/HIV_infant.htm (accessed March 2007).
(8.) Kotler DP. HIV infection and the gastrointestinal tract. AIDS 2005; 19: 107-117.
(9.) Castleman A, Seumo-Fosso E, Cogill B. Food and Nutrition Implications of Antiretroviral Therapy in Resource Limited Settings. Washington DC: Food and Nutrition Technical Assistance (FANTA) Project. DC: Academy for Educational Development, 2004.
(10.) Friis H. Micronutrients and HIV infection: a review of current evidence. World Health Organisation, 2005. Consultation on Nutrition and HIV/AIDS in Africa. Evidence, lessons and recommendations for action. Durban, South Africa, 10-13 April 2005.
(11.) Tang AM, Lanzillotti J, Hendricks K, et al. Micronutrients: current issues for HIV care providers. AIDS 2005; 19: 847-861.
(12.) Hussey G, Buys H, Cowburn C, Eley B, Hendricks M. Role of micronutrients in HIV infection. Southern African Journal of HIV Medicine 2005; 19: 18-22.
(13.) Coutsoudis A, Bobat RA, Coovadia HM, Kuhn L, Tsai WY, Stein ZA. The effects of vitamin A supplementation on the morbidity of children born to HIV-infected women. Am J Public Health 1995; 85: 1076-1081.
(14.) Hussey GD, Klein M. A randomized controlled trial of vitamin A in children with severe measles. N Engl J Med 1990; 323: 160-164.
(15.) Rahmathullah L, Underwood BA, Thulasiraj RD, et al. Reduced mortality among children in Southern India receiving a small weekly dose of vitamin A. N Engl J Med 1990; 23: 929-935.
(16.) Wiysonge CS, Shey MS, Sterne JA, Brockelhurst P. Vitamin A supplementation for reducing the risk of mother-to-child transmission on HIV infection. Cochrane Database Syst Rev 2005; Oct 19;(4): CD003648.
(17.) Coutsoudis A, Pillay K, Spooner E, Kuhn L, Coovadia HM. Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group. AIDS 1999; 13: 1517-1524.
(18.) Fawzi WW, Mbise RL, Hertzmark E, et al. A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania. Pediatr Infect Dis J 1999; 18: 127-133.
(19.) Humphrey JH, Iliff PJ, Marinda ET, et al.: the ZVITAMBO Study Group. Effects of a single large dose of vitamin A given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival and mortality. J Infect Dis 2006; 193: 860-871.
(20.) Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004; 351: 23-32.
(21.) Turpin JA, Vargo M, Meltzer MS. Enhanced HIV-replication in retinoid-treated monocytes. Retinoid effects mediated through mechanisms related to cell differentiation and to a direct transcriptional action on viral gene expression. J Immunol 1992; 148: 2539-2546.
(22.) Dietary Reference Intakes: Recommended Intakes for Individuals. Food and Nutrition Board, Institute of Medicine, National Academy of Sciences Dietary Reference Intakes, 2000, 2002. Washington, DC: National Academy Press. www. nap.edu. (In: Dwyer J. Nutritional requirements and dietary assessment. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, eds. Harrison's Principles and Practice of Internal Medicine. Vol. 1. 16th ed. New York: McGraw-Hill, 2005: 400-401.)
(23.) Jiamton S, Pepin J, Suttent R, et al. A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok. AIDS 2003; 17: 2461-2469.
(24.) Kaiser JD, Campa AM, Ondercin JP, Leoung GS, Pless RF, Baum MK. Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: A prospective, double-blinded, placebo-controlled trial. J Acquir Immune Defic Syndr 2006; 42: 523-528.
(25.) Beach R, Mantero-Atienza E, Shor-Posner G, et al. Specific nutrient abnormalities in asymptomatic HIV-1 infection. AIDS 1992; 6: 701-708.
(26.) Periquet B, Jammes N, Lambert W, et al. Micronutrient levels in HIV-1 infected children. AIDS 1995; 9: 887-893.
(27.) Sambrook P, Cooper C. Osteoporosis. Lancet 2006; 367: 2010-2018.
(28.) Madeddu G, Spanu A, Solinas P, et al. Bone mass loss and vitamin D metabolism impairment in HIV-patients receiving highly active antiretroviral therapy. Quarterly J Nuclear Med and Molecular Imaging 2004; 48: 39-48.
(29.) Wharton B, Bishop N. Rickets. Lancet 2003; 362: 1389-1400.
(30.) Academy of Science of South Africa. HIV/AIDS, TB and Nutrition. A Scientific Inquiry into the Nutritional Influences on Human Immunity with Special Reference to HIV Infection and Active TB in South Africa. Pretoria: Academy of Science of South Africa, 2007.
(31.) Sazawal S, Black RE, Ramsan M, et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomized, placebo-controlled trial. Lancet 2006; 367: 133-143.
(32.) Rayman MP. The importance of selenium to human health. Lancet 2000; 356: 233-241.
(33.) Hurwitz BE, Klaus JR, Llabre MM, et al. Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation. Arch Intern Med 2007; 167: 148-154.
(34.) Bobat R, Coovadia H, Stephen C, et al. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomized double-blind placebo-controlled trial. Lancet 2005; 366: 1862-1867.
(35.) Brooks WA, Santosham M, Naheed A, et al. Effect of weekly zinc supplements on incidence of pneumonia and diarrhea in children younger than 2 years in an urban, low-income population in Bangladesh: randomized double-blind controlled trial. Lancet 2005; 366: 999-1004.
(36.) Chandra RK. Excessive intake of zinc impairs immune function. JAMA 1984; 252: 1443-1446.
(37.) Bishop N. Rickets today--children still need milk and sunshine. N Engl J Med 1999; 341: 602-604.
(38.) Pettifor JM, Ross P, Wang J, Moodley G, Couper-Smith J. Rickets in children of rural origin in South Africa: is low dietary calcium a factor? J Paediatr 1978; 92: 320-324.
(39.) Faber M, Jofessar VB, Benade AJ. Nutritional status and dietary intakes of children aged 2-5 years and their caregivers in a rural South African community. Int J Food Sci Nutr 2001; 52: 401-411.
(40.) Bachmann MO, Booysen FLR. Economic causes and effects of AIDS in South African households. AIDS 2006; 20: 1861-1867.
(41.) Irlam JH. Micronutrient supplementation in children and adults with HIV infection. Cochrane Rev Abstract 2007, posted 04/01/2007. http://www.medscape.com/ viewarticle/514923 (accessed 10 September 2007).
4. NUTRITION AND PREGNANCY, LACTATION AND THE PREVENTION OF MOTHER-TO-CHILD TRANSMISSION (PMTCT)
Pregnancy and infancy are vulnerable periods in human life. In sub-Saharan Africa, 1 in 16 women dies in pregnancy or childbirth. This risk is 175 times higher than that in developed countries. (1) Of the 136 million babies born every year, 3.2 million are stillborn and 4 million die in the first month of life: 98% of these babies live in low-income and middle-income countries. (1) Health may be compromised by a variety of factors including maternal malnutrition, age, poverty, social disruption and chronic disease such as HIV/ AIDS and tuberculosis (TB). During pregnancy, the absence of specific nutrients, e.g. folate (neural tube defects), and the presence of dietary toxins, e.g. alcohol (the fetal alcohol syndrome), may directly affect the weight and well-being of the newborn. However, in developing countries intrauterine growth restriction is mainly due to poor maternal nutrition and infections including HIV. (2) Increased infant mortality and morbidity correlate strongly with low birth weight. (3) Premature birth is more common in the context of maternal HIV infection, a risk that has not been altered by the introduction of antiretroviral therapy (ART). (4) Low birth weight (<2 500 g at [greater than or equal to] 37 weeks) or small for gestational age (SGA) newborns remain at risk for significant morbid events such as hypertension, obesity, glucose intolerance and cardiovascular disease later in life; (5-6) 11% of births in developing countries fall into this category. (2) Nutritional requirements increase in pregnancy and lactation. HIV infection increases the energy needs of both the asymptomatic and the symptomatic. (2,7) HIV-infected women generally gain less weight during pregnancy than uninfected women, particularly in the third trimester (8) (Table 4.I).
Where antiretroviral (ARV) drugs are not available, rates of mother-to-child transmission (MTCT) are high at 25-45%. Intrauterine and intrapartum transmission account for 5-10% and 10-20% of this figure, respectively. (9,10) Depending upon its duration, the introduction of mixed feeds, maternal viral load, etc., breastfeeding may carry an additional 12-16% risk. (11) Contaminated maternal fluids--amniotic fluid, vaginal secretions, blood and breastmilk--ingested before birth, at birth or during breastfeeding, transmit virus to the baby. Maternal virus has been recovered from cells in the newborn's mouth shortly after birth. (12) The infant's punctured skin may be a further site of transmission: scalp electrodes, suction and forceps should be avoided during delivery. (13) Do micronutrients slow the natural progression of HIV infection? Can they reduce perinatal transmission? MTCT of HIV can be prevented, but in 2005 only 9% of pregnant women in low-income and middle-income countries received services to prevent transmission to their newborn babies, and only 9.2% of HIV-positive pregnant women received prophylactic ARVs. (14) Can improved maternal nutrition enhance the survival of the infected mother and her child?
4.2 VITAMINS, MICRONUTRIENTS AND THE PREVENTION OF PERINATAL HIV TRANSMISSION
Vitamin and micronutrient supplementation during pregnancy has not uniformly led to a reduction in MTCT. The Tanzanian vitamin intervention trials indicated reduced child mortality, improved pregnancy outcome and reduced transmission to the children of malnourished mothers with low lymphocyte counts. These studies have not been duplicated elsewhere, and the reported benefit was restricted to the use of micronutrients, excluding vitamin A. (14-18) Data from additional sites are needed to support these results. Prophylaxis with vitamin A in South Africa did not reduce MTCT. (19) Behind these results has been the observation that women with low serum retinol levels appear to transmit HIV more readily to their babies. (20-21) Kenyan reports correlate low serum retinol with increased viral shedding in vaginal/cervical fluids and in breastmilk. (22,23) Unfortunately these studies did not exclude an 'acute-phase/active inflammatory' response as the cause of low retinol levels: the low vitamin A levels may have had little direct relationship with the findings, and may have reflected advanced HIV disease itself, and a resulting increased risk of transmission. (24) In Zimbabwe a large single dose of vitamin A (400 000 IU) given to women after delivery had no protective effect against their subsequent acquisition of the virus. During the 2-year follow-up those with low baseline serum retinol levels and anaemia (haemoglobin <7 g/dl) were more likely to seroconvert. But the authors admit that confounding variables had not been adequately excluded. (25) Maternal viral load and severe maternal immunodeficiency--in particular a CD4 count below 200 cells/[micro]l--remain the major determinants of risk of transmission. (26-28) Only ART has been consistently shown to reduce maternal viral load and reduce perinatal HIV transmission. (29) Where malnutrition and HIV infection coexist, providing food and correcting specific nutritional deficiencies remains the appropriate response.
4.3 BREASTFEEDING AND THE RISK OF HIV TRANSMISSION
When deciding on a preventive strategy for Africa, one needs to take into account the importance of breastfeeding for child survival. (30) Breastfeeding protects infants from malnutrition, gastrointestinal and respiratory infections. (31) Mortality from these conditions is common in developing countries, where babies who are not breastfed in the first 2 months of life experience a 6-fold increase in death rate. (32) Breastmilk provides optimal nutrition for an infant--the milk is economical and safe, it fulfils the infant's total nutritional needs for the first 6 months of life, and it is an important component of the child's intake until 2 years of age. (33) It is important to note that iron supplementation may be given from 6 months onward to exclusively breastfed children who come from low-income areas. (34) On the other hand, the HIV-infected mother who breastfeeds has a 4-16% risk of transmitting virus to the child, depending on the duration and type of breastfeeding. (11,35,36) In rural KwaZulu-Natal, HIV prevalence rates in newborns increased from 14% at 6 weeks to 24% at 3-6 months in a mixed breastfeeding population. (33) Risk persists throughout the breastfeeding period and returns upon subsequent re-exposure to breastmilk with an increased risk relative to the duration of exposure. (35) Among exclusively breastfed infants, a transmission rate of 2-4% has been recorded at 6 months. (36,37) If an infected mother is to breastfeed her infant, the technique of exclusive breastfeeding must be followed.
Virus is present in both the cell-associated and cell-free components of breastmilk. (38) Direct viral invasion of the infant's gastrointestinal cells may alter the permeability of the child's gastrointestinal tract. (33) Childhood vitamin A deficiency is widespread in the developing world. This might further contribute to poor epithelial repair. Mixed feeds--breastmilk with a combination of water, formula, solids, teas, yoghurts, etc.--theoretically present the immature gastrointestinal tract with a variety of bacterial and food antigens. The resulting inflammatory activity is believed to promote viral penetration and facilitate viral entry into the infant's immune (gastrointestinal lymphatic) system. (33) In addition, mixed feeding is associated with sub-clinical mastitis, and with increased viral concentrations in breastmilk. Exclusive breastfeeding--offering the infant only breastmilk and no other source of nutrition--may present the infantile gastrointestinal tract with less inflammatory stress and less opportunity for viral transmission. (11,39-40)
Public health authorities recommend feeding choices on the basis of local infant mortality rates (IMRs). South Africa has a different IMR in each province, so a blanket policy is inappropriate. A recent model recommends that if the IMR is <25/1 000 live births, replacement feeding will give the best HIV-free survival. However where the IMR is >25/ 1 000 live births, exclusive breastfeeding produces the best outcomes. Indeed, where the IMR is >101/1 000 live births, replacement feeding results in a lower HIV-free survival than no intervention. (30)
Several factors may increase the risk of viral transmission through breastfeeding (41) (Table 4.II).
4.3.1 Breastfeeding: Exclusive or mixed?
ART through pregnancy, good viral suppression and the avoidance of breastfeeding have almost eradicated MTCT in the developed world. (4) For a minority of women in the developing world this approach can be followed provided formula feeds can be given in an acceptable, feasible, affordable, sustainable and safe manner. (42) But for the majority of mothers in southern Africa these 'AFASS' criteria cannot be met and the baby will need to be breastfed (see boxes, p. 44). Can transmission be prevented, or at least reduced, despite breastfeeding? Data suggest that exclusive breastfeeding for the first 6 months of life will reduce transmission risk and vulnerability to life-threatening childhood infections. (11,39-40) A 3- to 4-fold decrease in risk of transmission has been achieved when compared with non-exclusively breastfed cohort studies. (43) Congolese children born to both HIV-infected and uninfected mothers were at greater risk from death when not exclusively breastfed in the first 6 months of life. (44) Stopping breastfeeding before 6 months or at 4 months in studies in Malawi, Kenya, Uganda and Zambia all appear to increase the risk of infant mortality, often from diarrhoea. (43) Despite some earlier anxiety, breastfeeding does not increase maternal mortality. (45-46)
4.3.2 Is exclusive breastfeeding for 6 months possible in the South African context?
In a study looking at the HIV-1 transmission risk and survival associated with exclusive breastfeeding and other types of infant feeding, it was found that a much higher rate of exclusive breastfeeding was achieved through counselling and support for the mothers. (47) Facility-based or community-based antenatal and postnatal clinic support is associated with an increase in exclusive breastfeeding rates. (30)
A facility-based programme with increased rates of exclusive breastfeeding is the Mother Baby Friendly Hospital Initiative (MBFHI). This international programme aims to improve mother and child survival by changing hospital practices and by supporting, promoting and protecting breastfeeding. In South Africa there is a drive to make all health care facilities 'mother-baby friendly'. (30)
Mothers need to be assisted in making the best decision with regard to infant feeding. The following are some of the choices:
* exclusive breastfeeding: an infant only receives breast-milk and no other liquids or solids, not even water, with the exception of drops or syrups consisting of vitamins, minerals, supplements or medications.
* Commercial infant formula: a breastmilk substitute formulated industrially in accordance with international standards to satisfy the nutritional requirements of infants during the first months of life and up to the introduction of complementary foods.
Mixed breastfeeding is feeding with breastmilk, other fluids and pureed solids. The enhanced risk of HIV transmission is thought to result from maternal breast and nipple infections (mastitis) that result in an increase in the viral load of the milk, and the introduction of multiple foreign 'antigens', including bacteria, that compromise the integrity of the infant's gastrointestinal tract. (42) Mixed feeding is not a choice: Mothers do this by default. Where formula feeding cannot be provided within the AFASS guidelines, exclusive breastfeeding for a minimum of 6 months is recommended (Table 4.III). (43)
WHO/UNICEF recommends that women who do not know their HIV status should exclusively breastfeed for the first 6 months of the child's life with continued breastfeeding and complementary feeding until 2 years of age. (30)
4.3.3 When should breastfeeding be stopped?
When alternative choices are 'acceptable, feasible, affordable, sustainable and safe'. This is generally at or just before 6 months: maternal milk supplies are insufficient to cope with the energy and nutrient needs of children beyond this age, and additional food sources need to be introduced. (47)
* Mother must be counselled on the need to stop at 6 months.
* Prepare baby for weaning and plan other forms of comfort apart from breast. Crying is very distressing and is a reason why mothers revert to breastfeeding.
* Prepare family for weaning of child. Counsel re disclosure and the need for help.
* Plan how to feed. Get supply of formula feed ready and demonstrate.
* Plan for any breast difficulty, such as engorgement.
4.3.4 Where highly active antiretroviral therapy (HAART) is affordable or available, should HAART be continued after delivery and/or for the duration of breastfeeding?
ART for the mother
Women who require indefinite HAART will continue with ARVs after childbirth. Those with baseline CD4 counts above 200-350 cells/[micro]l and asymptomatic HIV infection will currently discontinue ARVs once their child is born. Continuing with ARVs for the duration of breastfeeding seems a reasonable approach provided adherence is reliable and viral suppression can be maintained. Two recent studies, the AMATA and MITRA trials from Rwanda and Tanzania, provided ARVs for the duration of breastfeeding and showed a transmission rate at 6 months of 1.4% and 5%, respectively. (48,49) These studies confirm reduced transmission to the infant. ARV drugs consumed by lactating women appear in breastmilk at levels that reduce breastmilk viral load. (50,51) Whether stopping therapy at the cessation of breastfeeding will lead to an increased risk of maternal viral resistance is currently unknown. (48,49,52)
ARV prophylactic therapy for the infant
The Botswana 'Mashi' study revealed that breastfed infants given only monotherapy with zidovudine (ZDV, AZT) as preventive therapy while being breastfed (not exclusive, usually 6 months) were not adequately protected. (Nevertheless, 7-month mortality was actually greater in the formula-fed infants. But by 18 months HIV-free survival was the same in both formula and breastfed groups. The children died of pneumonia and diarrhoea.) Few mothers commenced HAART before delivery (71 of a total of 1 200 women randomised), and few (only 82) started on ARVs during the 7 postpartum study months. The women were given zidovudine monotherapy from 34 weeks until delivery. Some also received intrapartum single-dose nevirapine. (53) In essence, the mothers were taking inadequate ARV therapy themselves while breastfeeding their infants. Giving ZDV monotherapy to these children during the breastfeeding period was inadequate post-exposure preventive therapy.
Weaning is a difficult time for both the mother and the child. Apart from the distress experienced by both, newly weaned infants frequently develop diarrhoea and anorexia. Mothers may experience breast engorgement, mastitis and abscess formation. Women need counselling and support during this time. The success of weaning is often dependent on prior contact with clinic staff and access of the mother to support. The weaning period is variable: 2-3 days in some cases, 2-3 weeks in others. In the context of maternal HIV infection, replacement feeds need to be introduced rapidly and the period of 'mixed' feeding kept as short as possible (A Coutsoudis, personal communication, June 2007).
Heat treatment of expressed breastmilk. Pasteurisation and 'flash-heating' decrease both the bacterial contamination and the HIV viral content of breastmilk. Loss of nutritional value is minimal. (54-55) Is heat treatment feasible in urban and informal settlements and rural situations in southern Africa? Pasteurisation requires heating the milk to 62.5[degrees]C for 30 minutes. With flash-heating, milk is rapidly brought to the boil and then immediately removed to cool to 37[degrees]C. Mothers who take this option need to be able to set aside time. A supportive domestic and social environment is essential. A recent Zimbabwean report notes that education and community discussion will improve the social acceptance of this modification to breastfeeding. (56)
4.3.6 Alternatives to breastfeeding
When infants are exclusively formula fed, the risk of postnatal HIV transmission is eliminated. This method of feeding is mainly chosen by women in developed countries. (30) From a meta-analysis of women in developing countries but of unknown HIV status, it was found that infants who were not breastfed and who received formula or replacement feeds have a 6-fold increase risk of death in the first 2 months of life. Between 2 and 3 months, the risk is 4-fold and 2.5-fold between 4 to 5 months. (30)
Formula or replacement feeds are only given when these are 'acceptable, feasible, affordable, sustainable and safe': the AFASS criteria. (43) Mothers who take this route must also be supported and counselled. It is imperative that the mother clearly understands the need for clean utensils, hygienic preparation and the correct measurement of the infant's feeds. (44) The International Code of Marketing of Breast Milk Substitutes discourages the promotion or recommendation by health professionals of a specific milk substitute. Being HIV positive does not automatically bar the mother from breastfeeding her infant. Mothers must decide for themselves which formula to use should they reject the free formula provided by the state. (44) No commercial product is a complete replica of breastmilk. Each has been modified for unique reasons and there is no 'best' formula: each is produced with the nutritional needs of all infants in mind. (33) The formula must be prepared in a clean environment and all equipment--bottles, nipples, mixers, lids (including that of the formula container)--must be thoroughly washed before use. Most children begin with a cow's milk-based formula feed.
In the South African PMTCT programme, mothers who so choose are supplied with free formula for the first 6 months of their child's life. Those mothers who exclusively breastfeed are given free formula for 6 months after weaning. (33) Table 4.IV outlines the recommended amount of formula appropriate to the age of the infant. These quantities provide sufficient energy for normal growth: keep in mind that HIV-infected infants will require at least 10% extra energy per day. These children will therefore need additional formula each day.
Since lactating mothers lose weight, in particular fat but not muscle, it is prudent to encourage increased nutrition during both pregnancy and lactation. Furthermore, it has been noted that CD4 cell counts decrease during lactation and hence good nutrition is imperative at this time. (57-58)
The energy and nutritional needs of pregnant and lactating women, particularly the malnourished and the HIV-infected, are increased. Limited data suggest that some multivitamins--vitamins B, C and E--may delay progression of infection, reduce the relative risk of dying from AIDS and improve CD4 counts and decrease viral loads. (17,59) In this context, the use of vitamin A has sometimes had conflicting results, including the possible promotion of MTCT. (17,19,59) With regard to the prevention of transmission, a beneficial role for other micronutrients--zinc, iron and selenium--in pregnancy has not been established. (24) Good maternal health is necessary for the welfare of the entire family. A sick mother increases the likelihood of death, stunted growth and poor development of her children. (1) While children remain vulnerable to vertical infection from their mothers, interventions aimed at reducing this risk are necessary. In addition to ART, exclusive breastfeeding now appears to offer some protection. But women find it difficult to do: it was seldom done in the studies from Zimbabwe and Uganda. (11,60) Health workers must be convinced and motivated if their patients (mothers and children) are to be protected from the virus and breastfeeding carried out successfully. (33) A considerable amount of effort is required by mothers, and the team of health workers around them, to ensure that exclusive breastfeeding is continued through to 6 months. Chen et al. make the perceptive remark that health workers 'are active agents of change'. (61) In the context of preventing MTCT, health workers need to be these 'agents of change'.
(1.) Fillipi V, Ronsmans C, Campbell OMR, et al. Maternal health in poor countries: the broader context and a call for action. Lancet 2006; 368: 1535-1541.
(2.) Walker SP, Wachs TD, Gardner JM, et al., and the International Child Development Steering Group. Child development: risk factors for adverse outcomes in developing countries. Lancet 2007; 369: 145-157.
(3.) Mofenson L, McIntyre JA. Advances and research direction in the prevention of mother-to-child HIV-1 transmission. Lancet 2000; 355: 2237-2244.
(4.) European Collaborative Study. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy. Clin Infect Dis 2005; 40: 458-465.
(5.) Barker DJP, Osmond C, Forsen TJ, Kajantie E, Eriksson JG. Trajectories of growth among children who had coronary events as adults. N Engl J Med 2005; 353: 1802-1809.
(6.) Harding JE. The nutritional basis of the fetal origins of adult disease. Int J Epidemiol 2001; 30: 15-23.
(7.) Hsu JW-C, Pencharz PB, Macallan D, Tomkins A. Macronutrients and HIV/AIDS: a review of current evidence. Consultation on Nutrition and HIV/AIDS in Africa: Evidence, lessons and recommendations for action. World Health Organization. Durban, South Africa, 10-13 April 2005.
(8.) Dabis F, Ekpini ER. HIV-1/AIDS and maternal and child health in Africa. Lancet 2002; 359: 2097-2104.
(9.) De Cock KM, Fowler MG, Mercier E, et al. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA 2000; 283: 1175-1182.
(10.) The Working Group on Mother-to-Child Transmission of HIV. Rates of mother-to-child transmission of HIV-1 in Africa, America and Europe: results from 13 perinatal studies. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 8: 506-510.
(11.) Illif PJ, Piwoz EG, Tavengwa NV, et al., the ZVITAMBO study group and Humphrey JH. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005; 19: 699-708.
(12.) Scarlatti G. Mother-to-child transmission of HIV-1: Advances and controversies of the 20th century. AIDS Reviews 2004; 6: 67-78.
(13.) Watts DH. Management of human immunodeficiency virus infection in pregnancy. N Engl J Med 2002; 346: 1879-1891.
(14.) Engle PL, Black MM, Behrman JR, et al., and the International Child Development Steering Group. Lancet 2007; 369: 229-242.
(15.) Fawzi WW, Msamanga G, Hunter D, et al. Randomized trial of vitamin supplements in relation to vertical transmission of HIV-1 in Tanzania. J Acquir Immune Defic Syndr 2001; 23: 246-254.
(16.) Fawzi WW, Msamanga G, Hunter D, et al. Randomized trial of effects of vitamin supplements on pregnancy outcomes and T-cell counts in HIV-1 infected women in Tanzania. Lancet 1998; 351: 1477-1482.
(17.) Fawzi WW, Msamanga GI, Hunter D, et al. Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality. AIDS 2002; 16: 1935-1944.
(18.) Fawzi WW, Msamanga GI, Wei R, et al. Effect of providing vitamin supplements to human immunodeficiency virus-infected, lactating mothers on the child's morbidity and CD4 cell counts. Clin Infect Dis 2003; 36: 1053-1062.
(19.) Coutsoudis A, Pillay K, Spooner E, Kuhn L, Coovadia HM, the South African Vitamin A Study Group. Randomized trial testing the effect of vitamin A on pregnancy outcomes and early mother-to-child transmission in Durban, South Africa. AIDS 1999; 13: 1517-1524.
(20.) Semba R, Miotti PG, Chiphangwi JD, et al. Maternal vitamin A deficiency and mother-to-child transmission of HIV-1. Lancet 1994; 343: 1593-1597.
(21.) Graham N, Bulterys M, Chao A. Effect of maternal vitamin A deficiency on infant mortality and perinatal HIV transmission. National Conference on Human Retroviruses and Related Infections. Johns Hopkins University, Baltimore, 1993..
(22.) John GC, Nduati RW, Mbori-Ngacha DA, et al. Genital shedding of human immunodeficiency virus type-1 DNA during pregnancy: association with immunosuppression, abnormal cervical or vaginal discharge and severe vitamin A deficiency. J Infect Dis 1997; 175: 57-62.
(23.) Nduati RW, John GC, Richardson BA, et al. Human Immunodeficiency virus type-1 infected cells in breast milk: association with immunosuppression and vitamin A deficiency. J Infect Dis 1995; 172: 1461-1468.
(24.) Friss H. Micronutrients and HIV infection: a review of current evidence. In: Consultation on Nutrition and HIV/AIDS in Africa: Evidence, lessons and recommendations for action. World Health Organization. Department of Nutrition for Health and Development. Durban, South Africa 10-13 April 2005.
(25.) Humphrey JH, Hargrove JW, Malaba LC, et al., and the ZVITAMBO Study Group. HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation. AIDS 2006; 20: 1437-446.
(26.) Shapiro D, Tuomala R, Pollack H, et al. Mother-to-child transmission risk according to antiretroviral therapy, mode of delivery, and viral load in 2895 US women (PACTG 367). Presented at the 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, 8-11 February 2004.
(27.) Leroy V, Montcho C, Manigart O, et al., for the Ditrame Study Group (ANRS 049 clinical trial). Maternal plasma viral load, zidovudine and mother-to-child transmission of HIV-1 in Africa: DITRAME ANRS 049a trial. AIDS 2001; 15: 517-522.
(28.) Newell M-L, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F, for the Ghent International AIDS Society (IAS) working group on HIV infection in women and children. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet 2004; 364: 1236-1243.
(29.) Volger MA. Update: Preventing mother-to-child transmission of HIV. Current HIV/AIDS Reports 2006; 3: 59-65.
(30.) Doherty T, Chopra M. South African Health Review. Pretoria: Health Systems Trust, 2006: 221-234.
(31.) Jason JM, Nieburg DB, Marks JS. Mortality and infectious disease associated with infant-feeding practices in developing countries. Pediatrics 1984; 74: 702-727.
(32.) World Health Organization Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. Lancet 2000; 355: 451-455.
(33.) Coutsoudis A. Breastfeeding and HIV. Best Practice & Research Clinical Obstetrics and Gynaecology 2005; 19: 185-196.
(34.) Torres MAA, Taddei JAAC. Anemia in low-income exclusively breastfed infants. J Paediatr 2006; 82(4): 284-288.
(35.) Breastfeeding and HIV International Transmission Study Group. Late postnatal transmission of HIV-1 in breast-fed children: an individual patient data meta- analysis. J Infect Dis 2004; 189: 2154-2166.
(36.) Rollins NC, Dedicoat M, Danaviah S, et al., for the Child Health Group. Prevalence, incidence and mother-to-child transmission of HIV-1 in rural South Africa. Lancet 2002; 360: 389-390
(37.) Coovadia HM, Rollins NC, Bland RM, et al. Mother to child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. Lancet 2007; 369: 1107-1116.
(38.) Embree JE, Njenga S, Datta P, et al. Risk factors for postnatal mother- child transmission of HIV-1. AIDS 2000; 14: 2535-2541
(39.) Coutsoudis A, Pillay K, Spooner E, Kuhn L, Coovadia HM, for the South Africa Vitamin A Study Group. Influence of infant feeding patterns on early mother-to-child transmission on HIV-1 in Durban, South Africa: a prospective cohort study. Lancet 1999; 354: 471-476.
(40.) Coutsoudis A, Pillay K, Kuhn L, Spooner E, Tsai W-Y, Coovadia HM, for the South African Vitamin A Study Group. Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS 2001; 15: 379-387.
(41.) Coutsoudis A. Infant feeding dilemmas created by HIV: South African experiences. From: Symposium: Women's Voices, Women's Choices: The Challenge of Nutrition and HIV/AIDS. J Nutr 2005; 1315: 956-959.
(42.) World Health Organization. New Data on the Prevention of Mother-to-Child Transmission of HIV and Policy Implications: Conclusions and Recommendations (Online). Geneva, 11-12 October 2000, approved 15 January 2001. http://www.unaids. org/publications/documents/mtct (accessed 10 February 2004).
(43.) World Health Organization. WHO HIV and Infant Feeding Technical Consultation held on behalf of the Interagency Task Team (IATT) on Prevention of HIV Infections in Pregnant Women, Mothers and their Infants. Geneva, 25-27 October 2006. http://www.who. int/child-adolescent-health/NUTRITION/HIV_infant.htm (accessed March 2007).
(44.) Ogundele MO, Coulter JBS. HIV transmission through breastfeeding: problems and prevention. Ann Trop Paediatr 2003; 23: 91-106.
(45.) Kuhn L, Kasonde P, Sinkala M, et al. Prolonged breast-feeding and mortality up to two years post-partum among HIV-positive women in Zambia. AIDS 2005; 19: 1677-1681.
(46.) Sedgh G, Speigelman D, Larsen U, Msamanga G, Fawzi W. Breastfeeding and maternal HIV-1 disease progression and mortality. AIDS 2004; 18: 1043-1049.
(47.) John-Stewart GC. Breast-feeding and HIV-1 transmission--how risky for how long? J Infect Dis 2007; 196: 1-3.
(48.) Arendt V, Ndimubanzi P, Vyankandondera J, et al. AMATA study: Effectiveness of antiretroviral therapy in breastfeeding mothers to prevent post-natal vertical transmission in Rwanda. 4th IAS Conference on HIV Pathogenesis Treatment and Prevention, Sydney, Australia, 22-25 July 2007. Abstract No. TUAX 102.
(49.) Kilewo C, Karlsson K, Ngarina M, et al. Prevention of mother-to-child transmission of HIV-1 through breastfeeding by treating mothers prophylactically with triple antiretroviral therapy in Dar Es Salaam, Tanzania--the MITRA PLUS study. 4th IAS Conference on HIV Pathogenesis Treatment and Prevention, Sydney, Australia, 22-25 July 2007. Abstract No. TUAX 101.
(50.) 55. Chung MH, Kiarie JN, Richardson BA, Lehman DA, Overbaugh J, John-Stewart GC. Breast milk HIV-1 suppression and decreased transmission: a randomized trial comparing HIVNET 012 nevirapine versus short-course zidovudine. AIDS 2005; 19: 1415-1422.
(51.) Moodley D, Moodley J, Coovadia H, et al. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 2003; 178: 725-735.
(52.) Palombi L, Marazzi MC, Voetberg A, Magid NA, and the DREAM Programme Prevention of Mother-To-Child Transmission Team. Treatment acceleration programme and the experience of the DREAM programme in prevention of mother-to-child transmission of HIV. AIDS 2007; 21 (suppl 4): S65-S71.
(53.) Thoir I, Lockman S, Smeaton LM, et al. Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana. JAMA 2006; 296: 794-805.
(54.) Israel-Ballard K, Chantry C, Dewey K, et al. Viral, nutritional, and bacterial safety of flash-Heated and Pretoria-pasteurized breastmilk to prevent mother-to-child transmission of HIV in resource-poor countries: A pilot study. J Acquir Immune Defic Syndr 2005; 40: 175-181.
(55.) Israel-Ballard K, Coutsoudis A, Chantry CJ, et al. Bacterial safety of flash-heated and unheated expressed breastmilk during storage. J Trop Pediatr 2006; 52: 399-405.
(56.) Israel-Ballard K, Maternowska C, Abrams B, et al. Acceptability of heat-treating breastmilk to prevent mother-to-child transmission of HIV in Zimbabwe: A qualitative study. J Hum Lact 2006; 22: 48-60.
(57.) Papathakis PC, Van Loan MD, Rollins NC, Chantry CJ, Bennich ML, Brown KH. Body composition changes during lactation in HIV-infected and HIV-uninfected South African women. J Acquir Immune Defic Syndr 2006; 43: 467-474.
(58.) Otieno PA, Brown ER, Mbori-Ngacha DA, et al. HIV-1 disease progression in breastfeeding and formula-feeding mothers: A prospective 2-year comparison of T cell subsets, HIV-1 RNA levels and mortality. J Infect Dis 2007; 195: 220-229.
(59.) Fawzi WW, Msanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004; 351: 23-32.
(60.) Magoni M, Bassani L, Okong P, et al. Mode of infant feeding and HIV infection in children in a programme for prevention of mother-to-child transmission in Uganda. AIDS 2005; 19: 433-437.
(61.) Chen L, Evans T, Anand S, et al. Human resources for health: overcoming the crisis. Lancet 2004; 364: 1984-1990.
5. HIV/AIDS IN INFANTS AND CHILDREN: NUTRITION
5.1 CHARACTERISTICS OF HIV INFECTION IN CHILDREN
* Children are not small adults.
* HIV infection in childhood differs from that in adults with regard to transmission, viral dynamics, the 'immaturity' of the immune system and clinical manifestations.
* More than 90% of infected children acquire their virus vertically, from an infected mother. (1) Most infections occur in the peri- or intrapartum periods. (2)
* Transmission via transfusion, sexual activity and drug abuse is infrequent in children.
* Depending upon whether it is mixed or exclusive and its duration, breastfeeding carries an additional postpartum risk of 4-16%. (3,4)
* Without antiretroviral therapy (ART), clinical disease in the vertically infected child takes a bimodal course: rapid progression with AIDS-defining symptoms and life-threatening complications in the first year of life in 10-25%. The natural course is slower in the remainder with a mean duration of more than 8 years until AIDS-defining symptoms occur. (5)
* Where infection is acquired at birth, the viral load rises rapidly in the first few months of life. If left untreated, these levels fall slowly in children surviving beyond the age of 4-5 years. These viral dynamics are significantly different to those of newly infected and untreated adults. (6)
Approximately 2.3 million children worldwide have HIV infection. Globally, only 115 000 of the 700 000 children requiring ART receive it. Just 15% of the need is actually being met. The vast majority of infected children live in Africa. In sub-Saharan Africa, only 80 000 children are currently receiving ART. (7)
5.2 UNDER-NUTRITION IN HIV-INFECTED CHILDREN
Under-nutrition is frequent in the children of Africa. (8-10) Many are also HIV-infected. (11,12) Growth stunting, an indicator of malnutrition, was present in 21.6% of South African children aged between 1 and 9 years; 10.3% of 1 - 3-year-olds were underweight. (13,14) Unemployment, poverty, food insecurity, malnutrition and vulnerability to infectious diseases define the cycle in which millions of Africans--adults and children--live their lives. (15) Most parents lack any formal nutritional education, and have inadequate skills to grow, purchase, prepare and provide food in sufficient variety to promote the growth of their children and ensure their own health. The child's survival is closely dependent on the health of the parent(s). In Malawi maternal mortality has risen 3-fold since 1990, (16) and in Botswana, Swaziland and Zimbabwe AIDS now causes more than half of the childhood deaths. (17) Africa's families are no longer the stable centre of communal life. Migratory labour, advancing urbanisation and the disappearance of traditional roots and values together with the social impact of the AIDS epidemic have shifted this centre. (18) For some 11 - 17 million South Africans the supply of food is unreliable; 38% of households report regular absence of meals. (17,18) Rural children and those in informal settlements around the cities are particularly at risk. (19,20) In addition, farming communities weakened by AIDS are likely to find it difficult to produce sufficient food for themselves or their surrounding region. With a reduced capacity to produce food, food insecurity is expected to persist into the future. (21) Africa's children may also be at risk from climate change: malnutrition, diarrhoea and malaria will increase should global warming affect the continent's weather patterns in the 21st century. (21,22)
5.2.2 Acute and chronic malnutrition in HIV-infected children
Up to 2% of under-5s in developing countries are acutely and severely malnourished. (15) Of Malawian children with severe acute malnutrition (SAM), 34% tested HIV-positive. (23) Fatality rates and slower recovery were frequent in these children. (17,23) Despite this, successful feeding programmes can be implemented in resource-poor communities. These interventions reduce hospital admissions and enhance public awareness. (24,25) A low mid-upper arm circumference (MUAC) is a rapid and useful measurement of the severity of malnutrition, though reduced height-for-weight scores and the presence of pitting oedema are also important clinical signs (see box). (10,26) Growth stunting is a frequent manifestation of chronic malnutrition. (27) This may begin very early, even during fetal development or soon after birth, and if not addressed, growth faulting will persist through childhood into adulthood. (28,29) In animals, early under-nutrition, iron deficiency, environmental toxins, poor stimulation and poor social interaction affect brain structure and function. Lasting cognitive and emotional defects result. (27) Similar changes have been reported in malnourished children. (29,30) Of children in developing regions, 39% are believed to be 'disadvantaged' in this way--stunted and/or living in poverty. Sub-Saharan Africa has the highest prevalence of such children, and is the only region where growth stunting and food insecurity are increasing. (30)
Poor growth is a sensitive indicator of the progression of HIV infection and is a strong and independent risk factor for death. (31,32) Indeed, linear growth faltering (loss of height/length) frequently anticipates the onset of new opportunistic disease in HIV-infected children. (31) Both the increased daily energy requirements of children infected with HIV and inadequate energy intake contribute to the accompanying loss of weight (31) (Table 5.I). In addition to providing nutrition, these children require control of their HIV infection. ART has been shown to enhance the child's gain of weight and height and to facilitate catch-up weight gain. (33,34) The child at risk must be identified before he/she becomes severely malnourished. Regular measurement of the child's weight and height/length is essential--as is the appropriate response of the health worker.
Poor growth of the HIV-infected child is a strong and independent predictor of death. Failure to achieve expected height or length goals in children may occur before the onset of clinical disease in infected children.
5.2.3 The assessment and measurement of nutritional status in children
Nutritional assessment should be routine and viewed as an 'early-warning system'. The assessment starts with a detailed history and is followed by a thorough examination. Though it is important to recognise wasting, it is a late sign. Action needs to be taken before wasting is clinically obvious. The response to interventions such as ART and nutritional supplements can be objectively measured. But the child who is responding will also take more interest in play activities and perform better at school. He/she will be happier and more contented.
Measurement: height/length, weight, head circumference and MUAC. In children the measurement of weight and height (length) is expressed as a Z-score--a comparison of the child to an international median or growth standard appropriate to age. (35) MUAC reflects lean body mass and not body fat. (36) Skinfold measurements provide information on subcutaneous fat but not visceral fat. Skinfold measurement is generally restricted to academic and referral centres. Similarly, whole body dual-energy X-ray absorptiometry (DEXA) scans have a limited role in Africa. Expense and expertise restrict this measurement to very few sites on the continent.
5.2.4 The management of acutely and chronically malnourished HIV-infected children
126.96.36.199 Major management goals
* Define the cause of the malnutrition: insufficient food, anorexia, opportunistic diseases such as tuberculosis and gastrointestinal infections (chronic diarrhoea), co-morbid disease such as diabetes, overwhelming and untreated HIV-infection. Correct the cause.
* Assess the HIV infection: Clinical stage, CD4 count and viral load. Does the child need antiretrovirals (ARVs)? Control the virus. Exclude opportunistic disease.
* Strengthen the long-term support of the child:
* Identify the primary and/or other caregiver(s): parent, aunt, sibling, etc.
* What are the nutritional and economic needs of the family and will the child be adequately cared for at home?
* Implement counselling and support. Access social and child grants. Work as a team: utilise social workers and local non-governmental organisations (NGOs) or train community workers to assist in counselling and with obtaining grants and support.
* Set targets: define the child's ideal weight and height and set a follow-up time-frame for achieving these targets. Ensure reliable follow-up: diarise dates, use phones (cell phone) and local community contacts. Ensure that the child has someone at home or in the community, to support him/her.
* Admit the severely malnourished child. Provide therapeutic feeding where needed. Plan long-term nutritional support: note that the energy needs of the HIV-infected are significantly higher than the uninfected. The World Health Organization (WHO) recommends meeting the increased resting energy needs by an additional 10% above usual requirements in asymptomatic adults and children and by an additional 20 - 50% during and immediately after severe illness. (31)
188.8.131.52 What food/supplementation should be used?
Increased energy and protein intake can best be achieved by using locally available foodstuffs and developing a locally appropriate, sustainable food-based intervention. Various supplements are available from the government clinics and hospitals of South Africa; their general acceptability awaits further evaluation. (37,38) 'Ready-to-use' therapeutic food (RUTF) is an energy-dense feed enriched with minerals and vitamins. This is provided for children with severe acute malnutrition. Therapeutic foods may also be prepared from local food sources and crops. (10) A variety of specialised nutritional products are also available from South African public health services. Nevertheless many children still do not have routine nutritional assessments, nor are all provided with supplements when needed. (38) Children need a balanced diet. Protein requirements remain at 12-15% of total energy intake. (31) ARVs may need to be considered as these will improve the child's appetite, promote weight gain and provide control of the underlying infection. (39)
184.108.40.206 Is micronutrient supplementation required?
Daily access to a diet that provides the full range of essential micronutrients is important. Randomised controlled trials (RCTs) indicate that vitamin A supplementation benefits young HIV-positive children: a single large oral dose of 50 000 IU before 6 months is followed by another single dose of 100 000 IU between 6 and 11 months and a further 200 000 IU every 6 months thereafter until the age of 5 years. (40,41)
Similarly zinc supplementation in HIV-infected and uninfected children with diarrhoea is recommended: zinc 10 mg daily x 2 weeks in those under 6 months of age and 20 mg daily x 2 weeks in those over 6 months. (42,43) Irrespective of HIV status, the WHO recommends a daily intake of 1 x the Recommended Nutrient Intake (RNI) of each essential vitamin and mineral. (31) Micronutrient deficiencies are endemic to many developing countries. Diversified diets, fortified foods and micronutrient supplements assist in preventing these deficiencies. Although two randomised controlled multivitamin trials incorporating among others large doses of the B-, C- and E-group vitamins have demonstrated benefit in HIV-infected Tanzanian and Thai adults, no similar paediatric data are currently available. (44,45) Iron supplementation is recommended for children with iron deficiency anaemia, but giving iron to children who are iron-replete may increase their risk of infections and should be avoided. (46,47)
5.3 THE METABOLIC SIDE-EFFECTS OF ART AND ITS MANAGEMENT IN CHILDREN
The benefits of ART outweigh its potential to cause harm. Drug-related metabolic side-effects are common but can be minimised or avoided with close supervision. In this regard the child on ART or his/her parent will often have noticed changes in body shape and appearance before these changes are observed by the doctor or nurse. The examination must take note of the child's general appearance, weight and height/length; particularly look for loss of fat on the face, upper and lower limbs and buttocks, an increase of abdominal fat and/or breast enlargement, a fat pad or 'buffalo hump' between the shoulders and firm non-tender enlargement of the liver. Fasting blood glucose and lipids, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol and triglycerides may be abnormal. These are measured annually or bi-annually or more frequently if abnormal. An isolated elevation of the alanine aminotransferase (ALT) level may suggest a fatty liver or hepatic steatosis. Fat in the liver may also be confirmed with a hepatic ultrasound or abdominal CT scan. (48)
The fat redistribution or lipodystrophy that complicates ARV drug use in adults occurs in children too. Various paediatric studies report a prevalence of 1 - 43%, though a recent review of children with a mean exposure to ARVs of 5.9 [+ or -] 2.4 years noted a considerably higher prevalence, viz. 73%. (49-52) The syndrome follows the use of protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs), in particular stavudine, didanosine and zidovudine, and the use of stavudine and didanosine together. (53-55) Children are at risk throughout childhood. (56) Insulin resistance is frequent, though overt hyperglycaemia and diabetes remain rare. (49) Serum lipids--cholesterols and triglycerides--are often elevated and an increase in the thickness of the wall of the carotid vessels has been noted in these children. While the actual risk of heart disease and stroke is currently unknown, it is likely to be significant over time. (57,58) All ethnic groups, including those living in Africa, appear to be at risk. (59,60) Metabolic abnormalities have also been reported in the absence of exposure to ART, though this is rare. (49,54)
Depleted levels of mitochondrial DNA and a variety of related abnormalities have been described in the cord blood of HIV-uninfected newborns exposed in utero to ARVs. (61,62) Mitochondrial DNA depletion and the inhibition of mitochondrial DNA polymerase-[gamma] are known consequences of NRTI therapy. (63) The PIs inhibit the activity of the glucose transporter protein 4 (GLUT 4), alter the degradation of the sterol regulatory element-binding protein 1 (SREBP-1) and apolipoprotein B, and inhibit the function of the low-density lipoprotein receptor-related protein (LPR), leading to increased lipid production and reduced triglyceride clearance from the circulation. (64)
5.3.1 Management of metabolic abnormalities
220.127.116.11 switching of ARVs
Adult 'switch' studies support the replacement of stavudine and zidovudine with abacavir and/or tenofovir. Bone demineralisation in children and infant monkeys exposed to tenofovir suggest caution in its use in this age group. (65) However, a recent study that switched children from a stavudine and PI-based ART to tenofovir and efavirenz noted improved biochemical parameters of bone resorption on tenofovir. (66) The NRTIs abacavir, lamivudine and emtricitabine carry little risk of either metabolic or mitochondrial toxicity and are safe in children. (67-69) Children switched from PI-based regimens to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen (efavirenz) improved total and LDL cholesterols and triglycerides. (49) The adult DAD study noted a similar effect, viz. lower serum lipid levels and fewer myocardial infarcts in patients on NNRTI- versus PI-based regimens. (70) Apart from atazanavir, most of the PIs are associated with lipid abnormalities and insulin resistance. Both boosted and un-boosted atazanavir may be less likely to cause fat abnormalities in adults, but there are no confirmatory data in children. (71-73) Adult studies suggest that nevirapine, an NNRTI, is less likely than efavirenz to elevate serum cholesterol. (74) Future antiretroviral classes--the fusion inhibitors, the CCR5 and the integrase inhibitors--hold out the hope of improved metabolic outcomes, but adult and paediatric data are limited and these agents are not currently registered for paediatric use in southern Africa. (75)
18.104.22.168 Diet and exercise
Obesity, high serum lipids and the lipodystrophy syndrome may all improve following a combination of resistance (mild weight training) and aerobic exercise. Exercise helps to maintain lean body mass and to restore lost lean tissue in children and adults. (76,77) Children enjoy playing and having fun: exercise strengthens relationships between parents and their children and is extremely important in the overall wellbeing of the child. In adults, regular high-frequency aerobic exercise--a minimum of 4 hours per week--has been accompanied by a decrease in intra-abdominal fat, increased HDL cholesterol levels and a small decrease in triglyceride levels. (78) Obese children need to lose weight. Those with elevated serum lipids need to reduce their total daily intake of fats, particularly saturated fats. However, carbohydrate loading from high-glycaemic foods such as ready-to-eat cereals, white bread and snack foods should be avoided. Diets that are low in fat but high in carbohydrates may reduce LDL but also HDL cholesterols. (78) High serum triglycerides may respond to diets rich in n-3 polyunsaturated fats such as canola or olive oil, soy and flaxseed oils, nuts (almonds, peanut, walnuts and pecans) and cold-water fish (salmon and mackerel), (79) but for many in Africa these foods are expensive and unobtainable, and a recent meta-analysis of n-3 fatty acid supplementation or dietary modification has not confirmed any cardiovascular benefit in adults. (78) Dietary advice must be simple and practical. Fish, poultry (without the skin) and lean red meat are recommended. Refer malnourished and obese children to a dietician wherever possible. Lifestyle modification programmes have been successful in adults, improving physical activity and reducing lipodystrophy scores and waist circumference and systolic blood pressures. (80) These programmes could be modified for use in children.
22.214.171.124 lipid-lowering agents in children
Children with elevated fasting lipids unresponsive to ARV-switching regimens, diet and exercise may require lipid-lowering agents, statins and fibrates. These should be used with caution as paediatric data are limited and the concomitant use of a PI with a statin may increase the risk of acute rhabdomyolysis. (49) While lovastatin has been approved for use in American adolescents with familial hypercholesterolaemia, its use--and that of simvastatin--in HIV-infected adults is discouraged. (81) Pravastatin, rouvastatin, atorvastatin and fluvastatin are used in adults and appear to be safe. (81) Similarly, fibrates may be required to bring down the triglycerides if modifications to diet, exercise and drug switches fail. Paediatric data are limited: interaction of the fibrates and the statins increases the risk of rhabdomyolysis and hepatitis, and interactions with the PIs may reduce the efficacy of the fibrates. (49)
126.96.36.199 Insulin resistance and hyperglycaemia in children on ARVs
Insulin resistance and elevated glucose levels have been reported in HIV-infected children, particularly those with lipodystrophy. (49) Insulin resistance in children is a risk factor for subsequent cardiovascular disease. (82) A fasting blood glucose and/or an oral glucose tolerance test should be checked as part of the diagnostic workup. (81,82) With regard to management there are very few paediatric data available. However, ARV-switch regimens and attention to dietary changes and exercise should be tried. In particular, obese children should be assisted to lose weight. Neither metformin nor the thiazolidenediones (e.g. rosiglitazone) have demonstrated sufficient efficacy and safety in adult studies to be recommended currently in HIV-infected children. (49,83)
188.8.131.52 Decreased bone mineral density in HIV-infected children
Bone mass increases in childhood and adolescence, peaks in early adult life and then declines slowly through adulthood. (84) Studies indicate a loss of bone mineral density (BMD) in HIV-infected adults before and after starting ART. Children with HIV infection demonstrate a similar decrease in BMD. (49,66) While the use of NRTIs and PIs has been incriminated, loss of bone mass may occur independent of exposure to the ARVs. The latter is probably a consequence of cytokine up-regulation within the bone and bone marrow following chronic activation of the immune system. (66,85,86) Mitochondrial toxicity has been suggested as the cause of ARV-related bone loss. (81,86) The nucleotide tenofovir has been associated with a significant decrease in BMD compared with stavudine. (87) Its use in osteopenic adults, in those at risk for osteoporosis and in children requires a regular review of BMD where feasible. (66,86) Malnutrition, weight loss and a background deficiency of vitamin D and calcium are common in the developing world and may further contribute to bone loss and weakness (88) (Table 5. II). The diagnosis and management of reduced BMD in HIV-infected children is currently unclear. DEXA scans are the best means of diagnosing subclinical osteopenia and osteoporosis. These scans are not widely available in sub-Saharan Africa. Discussion with a local paediatric expert is recommended. Where poor nutrition and specifically vitamin D and calcium deficiency have been confirmed or are likely, these nutrients must be replaced. The role of biphosphonates in children with documented loss of BMD remains ill defined. Alendronate has been used together with calcium and vitamin D in HIV-infected adults. BMD improved significantly in the group of adults on a biphosphonate compared with those given only calcium and vitamin D. (89) Discussion with a local metabolic specialist is recommended.
Children in Africa continue to be drawn into the HIV epidemic. Inadequate screening of at-risk mothers and failure to prevent mother-to-child-transmission permit this appalling situation to continue. Inadequate linear growth and failure to gain weight are important markers of malnutrition and of uncontrolled infection--HIV itself or an opportunistic disease such as tuberculosis. Small children frequently go without meals. Childhood stunting leads to restricted neurological development. This has consequences that follow the child into adulthood. Food security is expected to worsen as the HIV epidemic expands across southern Africa and as climate 'change' reduces the productivity of agricultural land. Many children on ART will develop the metabolic complications of ARV. Can lifestyle modification--exercise and diet--prevent these complications? Answers will require close surveillance. Adequate care demands the regular assessment of HIV-infected children and their assured access to a sympathetic and competent health system. Such children deserve the broadest participation and commitment of multiple sectors within society: a trained and functional health care system, a willing and supportive government, and a community that owns the epidemic and believes in the future of these children.
APPENDIX B Antiretroviral Therapy: Lipid and Glucose Side-Effects. (Tebas P. Cardiovascular Disease Preventior it Patients with HIV Infection. Expert column, CME, Medscape, http:www.medscape.com/viewarticle/548184, accessed March 2007.) Drug class and Changes in serum individual ARVs Changes in serum lipids glucose and insulin Nucleoside/nucleotide reverse transcriptase inhibitors (N/NtRTIs) Zidovudine Increase in TC and TG IR: increased insulin levels Stavudine Increase in TC and TG IR Didanosine Increase in TC and TG IR Tenofovir, abacavir, No significant effect No significant lamivudine and effect emtricitabine Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz Increase in TC, HDL, No significant LDL cholesterols, effect no effect on TG Nevirapine Increase in HDL, No significant no effect on TC, effect LDL or TG Protease inhibitors (Pls) Atazanavir No significant effect No significant effect Fosamprenavir Increase in TC and TG, No significant increase in HDL effect Indinavir Increase in TC and TG IR Lopinavir/ritonavir Increase in TC and TG IR (Kaletra) Nelfinavir Increase in LDL choles- No significant terol and TG, decrease effect in HDL Ritonavir: full dose Increase in TC and TG IR Saquinavir No significant effect No significant effect Tipranavir Increased TC and TG Unknown TC= total cholesterol; TG = triglycerides; IR = insulin resistance; LDL = low-density lipoprotein; HLD = high-density lipoprotein.
(1.) Walker N, Schwartlander B, Bryce J. Meeting international goals in child survival and HIV/AIDS. Lancet 2002; 360: 284-289.
(2.) Dabis F, Ekpini ER. HIV-1/AIDS and maternal and child health in Africa. Lancet 2002; 359: 2097-2104.
(3.) Illif PJ, Piwoz EG, Tavengwa NV, et al., the ZVITAMBO study group and Humphrey JH. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 2005; 19: 699-708.
(4.) Coutsoudis A. Breastfeeding and HIV. Best Practice & Research Clinical Obstetrics and Gynaecology 2005; 19: 185-196.
(5.) Greenberg AE, Dabis F, Marum LH, De Cock KM. HIV infection in Africa. In: Pizzo PA, Wilfert CM, eds. Pediatric AIDS--the Challenge of HIV Infection in Children and Adolescents. 3rd ed. Baltimore: Williams & Wilkins, 1998.
(6.) Palumbo PE, Raskino C, Fiskus S, et al. Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA 1998; 279: 756-761.
(7.) Gray GE. IAS 2007: Management of Pediatric HIV Infection, and Prevention of Mother-to-Child HIV Transmission. Medscape CME. http://www.medscape.com/ viewprogram/8057_pnt (accessed 14 November 2007).
(8.) Puoane T, Sanders D, Chopra M, et al. Evaluating the clinical management of severely malnourished children--a study of two rural district hospitals. S Afr Med J 2001; 91: 137-141.
(9.) Chopra M, Wilkinson D. Treatment of malnutrition. Lancet 1995; 345: 788.
(10.) Collins S, Dent N, Binns P, Bahwere P, Sadler K, Hallam A. Management of severe acute malnutrition in children. Lancet 2006; 368: 1992-2000.
(11.) Dabis F, Ekpini ER. HIV-1/AIDS and maternal and child health in Africa. Lancet 2002; 359: 2097-2104.
(12.) Ashworth A, Chopra M, McCoy D, et al. WHO guidelines for management of severe malnutrition in rural South African hospitals: effect on case fatality and the influence of operational factors. Lancet 2004; 363: 1110-1115.
(13.) Labradarios D, Steyn N, Maunder E, et al. The National Food Consumption Survey (NFCS): Children Aged 1 - 9 Years, South Africa, 1999. Pretoria: Department of Health, 2000: 193-206.
(14.) Bachmann MO, Booysen FLR. Economic causes and effects of AIDS in South African households. AIDS 2006; 20: 1861-1867.
(15.) UNICEF. UNICEF global database on child malnutrition. http://www.childinfo.org/ areas/malnutrition/wasting.php (accessed 20 December 2005).
(16.) National Statistical Office, ORC Macro. Malawi Demographic and Health Survey 2004. December 2005. http://www.nso.malawi.net/data_on_line/demography/ dhs2004.html (accessed 16 September 2006).
(17.) Black RE, Morris SS, Bryce J. Where and why are 10 million children dying every year? Lancet 2003; 361: 2226-2234.
(18.) Erik M, Albertse EC. Household food insecurity as a potential risk factor for stunting among young children in South Africa. Ann Nutr Metab 2001; 45: Suppl 1, 526.
(19.) Sclar ED, Garau P, Carolini G. The 21st century health challenge of slums and cities. Lancet 2005; 365: 901-903.
(20.) Sanchez PA, Swaminathan MS. Hunger in Africa: the link between unhealthy people and unhealthy soils. Lancet 2005; 365: 442-444.
(21.) de Waal A, Whiteside A. New variant famine: AIDS and food crisis in southern Africa. Lancet 2003; 362: 1234-1237.
(22.) Haines A, Kovats RS, Campbell-Lendrum D, Corvalan C. Climate change and human health: impacts, vulnerability, and mitigation. Lancet 2006; 367: 2101-2109.
(23.) Kessler L, Daley H, Malenga G, Graham S. The impact of the human immunodeficiency virus type 1 on the management of severe malnutrition in Malawi. Ann Trop Paediatr 2000; 20: 50-56.
(24.) UNICEF. Children on the brink: a joint report on orphan estimates and program strategies. http://www.unicef.org/publications/pub_children_on_the_brink_en.pdf (accessed 9 September 2004).
(25.) Manary MJ, Ndkeha MJ, Ashorn P, Maleta K, Briend A. Home based therapy for severe malnutrition with ready-to-use food. Arch Dis Child 2004; 89: 557-561.
(26.) Arpadi SM. Growth failure in HIV-infected children. In: Proceedings of the World Health Organization Consultation on Nutrition and HIV/AIDS in Africa: Evidence, Lessons and Recommendations for Action. Durban, South Africa, 10-13 April 2005.
(27.) Engel PL, Black MM, Behrman JR, et al., and the International Child Development Steering Group. Strategies to avoid the loss of developmental potential in more than 200 million children in the developing world. Lancet 2007; 369: 229-242.
(28.) Webb S, Monk C, Nelson C. Mechanism of postnatal neurobiological development: implications for human development. Dev Neuropsychol 2001; 19: 147-171.
(29.) McGregor SG, Cheung YB, Cueto S, Glewe P, Richter L, Strupp B, and the International Child Development Steering Group. Developmental potential in the first 5 years for children in developing countries. Lancet 2007; 369: 60-70.
(30.) Walker SP, Wachs TD, Meeks J, et al., and the International Child Development Steering Group. Child development: risk factors for adverse outcomes in developing countries. Lancet 2007; 369: 145-157.
(31.) Executive summary. World Health Organization Consultation on Nutrition and HIV/ AIDS in Africa: Evidence, lessons and recommendations for action. Durban, South Africa, 10-13 April 2005.
(32.) Fontana M, Zuin G, Plebani A, Bastoni K, Visconti G, Principi N. Body composition in HIV-infected children: relations with disease progression and survival. Am J Clin Nutr 1999; 69: 1283-1286.
(33.) Guillen S, Ramos JT, Resino R, Bellon JM, Munoz MA. Impact on weight and height with the use of HAART in HIV-infected children. Pediatr Infect Dis J 2007; 26: 334-338.
(34.) Nachman SA, Lindsey JC, Moye J, et al., for the Pediatric AIDS Clinical Trials Group 377 Team. Growth of human immunodeficiency virus-infected children receiving highly active antiretroviral therapy. Pediatr Infect Dis J 2005; 24: 352-357.
(35.) World Health Organization. Physical status: the use and interpretation of anthropometry. Report of a WHO expert committee. World Health Organ Tech Rep Ser 1995; No. 854.
(36.) Young H, Borrel A, Holland D, Salama P. Public nutrition in complex emergencies. Lancet 2004; 364: 1899-1909.
(37.) Department of Health. The South African Comprehensive HIV and AIDS Care, Management and Treatment Plan. Pretoria: Department of Health, 2007.
(38.) Harman C. Personal communication, dietician, Paediatric HIV Unit, Chris Hani Baragwanath Hospital, Soweto, 2007.
(39.) Chiappini E, Galli L, Tovo P-A, et al. Virologic, immunologic and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection. AIDS 2006; 20: 207-215.
(40.) Fawzi WW, Mbise RL, Hertzmark E, et al. A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virusinfected and uninfected children in Tanzania. Pediatr Infect Dis J 1999; 18: 127-133.
(41.) Coutsoudis A, Bobat RA, Coovadia HM, Kuhn L, Tsai WY, Stein ZA. The effects of vitamin A supplementation on the morbidity of children born to HIV-infected women. Am J Public Health 1995; 85: 1076-1081.
(42.) Bobat R, Coovadia H, Stephen C, et al. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomized double-blind placebo-controlled trial. Lancet 2005; 366: 1862-1867.
(43.) Hussey G, Buys H, Cowburn C, Eley B, Hendricks M. Role of micronutrients in HIV infection. Southern African Journal of HIV Medicine 2005; 19: 18-22.
(44.) Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004; 351: 23-32.
(45.) Jiamton S, Pepin J, Suttent R, et al. A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok. AIDS 2003; 17: 2461-2469.
(46.) Weinberg GA, Boelaert JR, Weinberg ED. Iron and HIV infection. In: Friis H, ed. Micronutrients and HIV Infection. Boca Raton, Calif.: CRC Press, 2001: 135-157.
(47.) Friis H. Micronutrients and HIV infection: a review of current evidence. World Health Organization Consultation on Nutrition and HIV/AIDS in Africa: Evidence, lessons and recommendations for action. Draft. Durban, South Africa, 10-13 April 2005, pp. 23-25.
(48.) Pol S, Lebray P, Vallet-Pitchard A. HIV infection and hepatic enzyme abnormalities: Intricacies of the pathogenic mechanisms. Clin Infect Dis 2004; 38: Suppl 2, S65-72.
(49.) McComsey GA, Leonard E. Metabolic complications of HIV therapy in children. AIDS 2004; 18: 1753-1768.
(50.) European Paediatric Lipodystrophy Group. Antiretroviral therapy, fat redistribution and hyperlipidaemia in HIV-infected children in Europe. AIDS 2004; 18: 1443- 1451.
(51.) Beregszaszi M, Dolifus C, Levine M, et al. Longitudinal evaluation and risk factors of lipodystrophy and associated metabolic changes in HIV-infected children. J Acquir Immune Defic Syndr 2005; 40: 161-168.
(52.) Ene L, Duiculescu D, Radoi R. High prevalence of lipodystrophy syndrome in a group of antiretroviral experienced adolescents. 11th European AIDS Conference/EACS, 24-27 October 2007, Madrid, Spain. Abstract P9.3/01.
(53.) Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000; 356: 1423-1430.
(54.) Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005; 352: 48-62.
(55.) Arpadi SM, Cuff PA, Horlick M, Wang J, Kotler DP. Lipodystrophy in HIV- infected children is associated with high viral loads and low CD4+ lymphocyte count and CD4+ lymphocyte percentage at baseline and use of protease inhibitors and stavudine. J Acquir Immune Defic Syndr 2001: 27: 30-34.
(56.) Taylor P, Worrell C, Steinberg SM, et al. Natural history of lipid abnormalities and fat redistribution among human immunodeficiency virus-infected children receiving long-term protease inhibitor-containing, highly active antiretroviral therapy regimens. Pediatrics 2004; 114: e235-e242.
(57.) McComsey GA, O'Riordan M, Hazen SL, et al. Increased carotid intima media thickness and cardiac biomarkers in HIV infected children. AIDS 2007; 21: 921- 927.
(58.) Charakida M, Donald AE, Green H, et al. Early structural and functional changes of the vasculature in HIV infected children. Impact of disease and antiretroviral therapy. Circulation 2005; 112: 103-109.
(59.) Mutimara E, Stewart A, Rheeder P, Crowther NJ. Metabolic function and the prevalence of lipodystrophy in a population of HIV-infected African subjects receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2007; 46: 451-455.
(60.) Pujari SN, Dravid A, Naik E, et al. Lipodystrophy and dyslipidaemia among patients taking first-line World Health Organization-recommended highly active antiretroviral therapy regimens in western India. J Acquir Immune Defic Syndr 2005; 39: 199-202.
(61.) Divi RL, Walker VE, Wade NA, et al. Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to combivir. AIDS 2004; 18: 1013-1021.
(62.) Brogly SB, Ylitalo N, Mofenson LM, et al. In utero nucleoside reverse transcriptase inhibitor exposure and signs of possible mitochondrial dysfunction in HIV- uninfected children. AIDS 2007; 21: 929-938.
(63.) Cossarizza A, Moyle G. Antiretroviral nucleoside and nucleotide analogues and mitochondria. AIDS 2004; 18: 137-151.
(64.) Sweeney LL, Brennan AM, Mantzoros CS. The role of adipokines in relation to lipodystrophy. Editorial Review. AIDS 2007; 21: 895-904.
(65.) Bartlett JG, Gallant JE. 2007 Medical Management of HIV Infection. Baltimore, Md: Johns Hopkins Medicine Health Publishing Business Group, 2007: 316-317.
(66.) Mora S, Zamproni I, Cafarelli L, et al. Alterations in circulating osteoimmune factors may be responsible for high bone resorption rate in HIV-infected children and adolescents. AIDS 2007; 21: 1129-1135.
(67.) Moyle GJ, Sabin C, Cartledge J, Reilly G. Lipid changes in a randomized, 48-weeks, open-label comparative study of tenofovir DF vs. abacavir as substitutes for a thymidine analog in persons with lipoatrophy: the RAVE study. Program and abstracts of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, 16-19 December 2005, Washington, DC. Abstract H-340.
(68.) Martin A, Smith DE, Carr A, et al., for the Mitochondrial Toxicity (MITX) Study Group. Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. AIDS 2004; 18: 1029- 1037.
(69.) Llibre JM, Domingo P, Palacios R, et al., and the Lipo-Rec Study Group. Sustained improvement of dyslipidaemia in HAART-treated patients replacing stavudine with tenofovir. AIDS 2006; 20: 1407-1414.
(70.) The DAD Study Group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356: 1723-1735.
(71.) Noor MA, Flint OP, Maa J-F, Parker RA. Effects of atazanavir/ritonavir and lopinavir/ ritonavir on glucose uptake and insulin sensitivity: demonstrable differences in vitro and clinically. AIDS 2006; 20: 1813-1821.
(72.) Johnson M, Grinsztejn B, Rodriguez C, et al. 96-week comparison of once daily atazanavr/ritonavir and twice daily lopinavir/ritonavir in patients with multiple virologic failures. AIDS 2006; 20: 711-718.
(73.) McComsey G, Malan N, Yang R, et al. Body composition changes in ARV-naive subjects treated with atazanavir (ATV) or atazanavir/ritonavir (ATV/RTV)-based once daily HAART: BMS A1424089 96 week CT and DEXA data. 11th European AIDS Conference/EACS, 24-27 October 2007, Madrid. Abstract P9.3/04.
(74.) Friis-Moller N, Weber R, Reiss P, et al., for the DAD Study Group. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study. AIDS 2003; 17: 1179-1193.
(75.) Lundgren J and Panel Members, European AIDS Clinical Society (EACS). Guidelines on the Prevention and Management of Metabolic Diseases in HIV. October 2007, p. 31. http://www.eacs.eu/guide/index.htm (accessed 1 November 2007).
(76.) Smith BA, Neidig JL, Nickel JT, Mitchell GL, Para MF, Fass RJ. Aerobic exercise: effects on parameters related to fatigue, dyspnea, weight and body composition in HIV- infected adults. AIDS 2001; 15: 593-601.
(77.) Jones SP, Doran DA, Leatt PB, Maker B, Pirmohamed M. Short-term exercise training improves body composition and hyperlipidaemia in HIV-positive individuals with lipodystrophy. AIDS 2001; 15: 2049-2051.
(78.) Brunzell JD. Hypertriglyceridemia. N Engl J Med 2007; 357: 1009-1017.
(79.) Gerber J, Kitch D, Aberg J, et al. The safety and efficacy of fish oil in combination with fenofibrate in subjects on ART with hypertriglyceridemia who had an incomplete response to either agent alone: results of A5186 [abstract 146]. In: Program and Abstracts of the 13th Conference on Retroviruses and Opportunistic Infections. Alexandria, Va.: Foundation for Retrovirology and Human Health, 2006: 100.
(80.) Fitch KV, Anderson EJ, Hubbard JL, et al. Effects of a lifestyle modification program in HIV-infected patients with the metabolic syndrome. AIDS 2006; 20: 1843-1850.
(81.) Wohl DA, McComsey G, Tebas P, et al. Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy. Clin Infect Dis 2006; 43: 645-653.
(82.) Steinberger J, Daniels SR. Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity and Metabolism). Circulation 2003; 107: 1448-1453.
(83.) Hadigan C, Mazza S, Crum D, Grinspoon S. Rosiglitazone increases small density lipoprotein concentration and decreases high-density lipoprotein particle size in HIV-infected patients. AIDS 2007; 21: 2543-2546.
(84.) Mosekilde L. Sex-differences in age-related loss of vertebral trabecular bone mass and structure: biomechanical consequences. Bone 1989; 10: 425-432.
(85.) Mondy K, Tebas P. Emerging bone problems in patients infected with human immunodeficiency virus. Clin Infect Dis 2003; 36: Suppl 2, S101-105.
(86.) Amorosa V, Tebas P. Bone disease and HIV infection. Clin Infect Dis 2006; 42: 108-114.
(87.) Staszewski S, Gallant J, Pozniak A, Suleiman J. Favourable metabolic profile for tenofovir sioproxil fumarate (TDF) versus stavudine (d4T) when used in combination with lamivudine and efavirenz in antiretroviral-naive patients: 96 week interim results. 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment, July 2003, Paris (abstract 562).
(88.) Pettifor J. Nutritional rickets: deficiency of vitamin D, calcium or both? Am J Clin Nutr 2004; 80: 1725S-1729S.
(89.) McComsey GA, Kendall MA, Tebas P, et al. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS 2007; 21: 2473-2482.
(90.) Lindsay R, Cosman F. Osteoporosis. In: Kasper DL, Braunwald E, Fauci AS, et al., eds. Harrison's Principles and Practice of Internal Medicine. Vol. II. 16th ed. New York: McGraw-Hill, 2005: 2268-2278.
6. FOOD, DRUGS, HERBS AND HIV INFECTION
6.1 FOOD AND DRUG INTERACTIONS
Food and drug interactions are important in the management of HIV-infected patients. Table 6.I sets out several of the known interactions with the antiretroviral (ARV) class of medicines.
6.2 WEBSITES WITH INFORMATION ABOUT DRUG AND DRUG INTERACTIONS
Food and drug interactions: www.foodmedinteractions.com
Liverpool HIV Pharmacology Group: www.hiv-druginteractions.org
HIV/AIDS Treatment Information Service: www.hivatis.org
Johns Hopkins AIDS Service: www.hopkins-aids.edu
International Association of Physicians in AIDS Care: www.iapac.org
6.3 HERBS, FOOD, TRADITIONAL MEDICINES AND ARV INTERACTIONS
African potato (Hypoxis hemerocallidea, and Hypoxis sp.). Common names for the African potato are 'magic muthi, yellow stars, star-lily, sterblom, gifbol, lotsane and molikharatsa'. (2) Plant sterols and sterolins and a glycoside, hypoxoside (rooperol) are present in the root of this plant. The African potato has been shown to induce activity of the nuclear pregnane X receptor (PXR) and to inhibit cytochrome P3A4 (CYP3A4). PXR activation promotes a P-glycoprotein dependent drug-efflux mechanism. Enhanced efflux and elimination may therefore reduce the bioavailability of other intestinally absorbed drugs such as the ARVs. This system also operates in the nervous system and its activation may decrease drug concentrations in the brain and spinal cord. (3,4) Clinical studies with the African potato were discontinued prematurely after its use led to bone marrow failure in HIV-infected patients. These subjects also experienced a significant fall in total lymphocyte and CD4 cell counts. (5,6) There is no scientific basis for its use in HIV patients at this time.
Aloe vera (A. barbadensis). Dried exudate from the aloe leaf contains anthranoids that behave as laxatives. (7) Although the gel or juice made from the aloe plant itself does not contain anthranoids, contamination during preparation is not unusual. A rapid intestinal drug transit time and/or overt diarrhoea may result in diminished absorption of medication such as the ARVs. Patients should be cautioned.
Beetroot. This vegetable is a food source. There is no scientific support for a role as an 'immune booster' or as an antiviral agent. Beetroot is not a significant source of dietary iron.
Dagga (marijuana, hashish). The psychoactive components of dagga are the cannabinoids. Oral cannabinoids (dronabinol) and dagga/marijuana (smoked) are sometimes used to stimulate appetite and control nausea. Weight gain has been inconsistent in clinical trials. When gain is achieved, this has been predominantly fat. Dronabinol use is therefore not generally recommended for the purpose of weight gain in HIV-positive patients. (8) With regard to drug interactions, animal studies suggest an inhibitory effect involving the CYP3A and CYP2C families of liver enzymes. This does not appear to result in significant alterations of plasma concentrations of the PIs, indinavir and nelfinavir. (9) Caution is recommended.
Echinacea (E. augustifolia, E. purpurea). Although this herb is sometimes taken as an 'immune booster', there is no scientific support for this. It is an inhibitor of CYP3A4 in vitro but an effect on ARVs has not been studied. It does not have any role in the management of HIV-infected patients. (4)
Garlic (Allium sativum). Garlic is an inducer of CYP3A4 and its use together with the protease inhibitor, saquinavir, has led to decreased blood levels of the latter. (10) Levels of saquinavir remained 30-40% below baseline even after a 10-day post-administration washout period. Two case reports indicate that co-administration of garlic and ritonavir may enhance the gastrointestinal toxicity of garlic, i.e cause abdominal discomfort, nausea and pain. (4,11) Garlic may increase the risk of bleeding: Patients with clotting abnormalities (e.g. low platelets, haemophilia), those on anticoagulants and those awaiting surgery are advised to stop taking garlic. (7) And as with the herbs, danshen, dong quai and papaya, garlic has been noted to interfere with platelet function. (7) Randomised controlled trials of garlic in non-HIV-infected subjects have shown small, short-term benefit to some lipid and antiplatelet factors. These findings have been disputed. (12) There is no evidence that garlic has any role in the management of the HIV-infected patient.
Ginkgo (Ginkgo biloba) and Siberian ginseng (Eleutherococcus senticosus). These compounds are unlikely to cause significant interactions with the ARVs. (4) However, the ginkolides inhibit platelet activating factor. Spontaneous subarachnoid haemorrhage and subdural haematoma have been reported and therefore caution is advised in any patient with a bleeding diathesis. (7) Mania has been reported in patients taking Asian ginseng. Caution is advised in any confused patient. (12)
Goldenseal (Hydrastis canadensis) inhibits CYP3A4. Studies with the PI, indinavir, indicated no change in drug pharmacokinetics, though midazolam levels increased significantly. Caution is recommended in patients taking ARVs. (4)
Grapefruit juice. Grapefruit contains the flavonoids, naringenin and furanocoumarin bergamottin--inhibitors of intestinal CYP3A4. (4) Orally administered medications thus bypass intestinal metabolism when given together with grapefruit juice. This results in greater intestinal absorption of these medications. Saquinavir's area under the curve (AUC)--though not that of indinavir or amprenavir--is increased by 50-150% when given simultaneously with grapefruit juice. Concentrations of flavonoids in an individual grapefruit and related products (fruit juice) vary. Consequently individual drug interactions are therefore difficult to predict. (13) Patients are generally warned against the use of grapefruit juice if taking ARVs.
Milk thistle (Silybum marianum). There appear to be no important interactions between this herb and the ARVs. (4)
Olive oil. There is no scientific support for the use of virgin olive oil as an 'immune booster' in HIV-positive people. However the use of a monounsaturated fat instead of polyunsaturated fats in patients on PIs and NRTIs with lipid-related metabolic side-effects is prudent.
Senna and laxative herbs (Cassia senna, C. angustifolia), cascara sagrada (Rhamnus purshiana), frangula (Rhamnus frangula), yellow dock (Rumex crispus), Chinese rhubarb (Rheum officinale). These are anthranoid-containing herbs and will cause diarrhoea. This may compromise gastrointestinal absorption of drugs. These herbs are not recommended. (7)
Skullcap utilises the CYP3A4 pathway for its metabolism and may influence the HIV drugs. This herb is not recommended for use in HIV-positive patients.
St John's Wort, SJW (Hypericum perforatum). This herb is used as an antidepressant and anxiolytic, though this indication is not supported by evidence-based studies. (12) A major constituent, hyperforin, induces hepatic CYP3A4 production. Substrates of CYP3A4 are rapidly metabolised. Consequently, plasma concentrations of both the NNRTIs and the PIs decrease significantly--to levels that permit the failure of viral control. Use of SJW with nevirapine, efavirenz and all the PIs is therefore contraindicated. A further constituent, hypericin, induces the production in vitro of the drug-efflux protein, P-glycoprotein. (12) This may cause medication to be more rapidly eliminated from the body. SJW also interferes with the biokinetics of other commonly prescribed drugs, e.g. amitriptyline, oral contraceptives, the statins (simvastatin) and warfarin. (12) SJW has no place in the management of HIV-positive patients.
Sutherlandia (Sutherlandia fructens sp. Microphlylla). Compounds derived from this flowering shrub are used throughout southern Africa and are known by a variety of names: unwele, insiswa, mukakana, phetola, lerumolamadi, cancerbush (kankerbos). Sutherlandia activates PXR, inhibits CYP3A4, and enhances the activity of the efflux protein, P-glycoprotein. As these metabolic pathways are shared by the ARV drugs, adverse interactions can be expected. (2,3) Controlled clinical trials with Sutherlandia are currently underway (Wilson D, personal communication, July 2007). Results are not yet available, and at this time this herb has no proven role in the HIV clinic.
6.4 COMMENT AND CONCLUSION
For many in Africa, traditional medicine and local herbs constitute the most accessible form of health care. (6) Notwithstanding their widespread availability and use over many decades, African traditional medicines have yet to be given a clear role in the management of HIV and AIDS. No single traditional agent either cures or in some way controls HIV infection. Are there alternative remedies? Is there better treatment? ARV therapy addresses this hope. What if any, is the role of herbs and traditional medicines in the HIV epidemic? A traditional healer comments: 'In the African traditional setting, the question, "Why am I ill?" is more important than, "What is the nature of my illness? It follows therefore, that a detailed biomedical explanation based on the germ theory is foreign and irrelevant to African concepts of illness.' (14) The AIDS epidemic points to the need to resolve the deep impasse between Western medicine and the traditional healing systems of Africa. Where the virus is denied, who needs to be counselled and tested? Who will use a condom when engaging in sex? Why bother to prevent the spread of the virus?
Truth, the assembly of facts that can be scrutinised, reproduced and verified, forms the basis of modern scientific medicine. A similar evidence-based examination of traditional medicine must occur if its claims to success are to be believed. Ethical principles underlie the practice of modern medicine: 'Primum non nocere' (first do no harm), autonomy, beneficence, non-malificence, and justice. All Africa's people ought to be assured that these rights operate irrespective of the healing system they follow. (15) Where both traditional and scientific systems subscribe to these ethical values, there is hope that the two may find common ground--and possibly the way forward to future collaboration. At this time no traditional 'remedy' can be recommended without an adequate assessment of its efficacy and toxicity. These data are still awaited with regard to herbs and traditional approaches to HIV care and management.
(1.) Nerad J, Romeyn M, Silverman E, et al. General Nutrition Management in Patients Infected with Human Immunodeficiency Virus. Clin Infect Dis 2003; 36: Suppl 2, S52-62.
(2.) Mills E, Cooper C, Seely D, Kanfer I. African herbal medicines in the treatment of HIV: Hypoxis and Sutherlandia fructescens. An overview of evidence and pharmacology. Nutr J 2005; 4: 19.
(3.) Mills E, Foster BC, van Heeswijk R, Phillips E, Wilson K, Leonard B, Kosuge K, Kanfer I. Impact of African herbal medicines on antiretroviral metabolism. AIDS 2005; 19: 95-97.
(4.) Lee LS, Andrade ASA, Flexner C. Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects. Clin Infect Dis 2006; 43: 1052-1059.
(5.) The Nutritional Information Center (NICUS), Stellenbosch University, Cape, SA. www.sun.ac.za/nicus (accessed October 2004).
(6.) Mills E, Cooper C, Kanfer I. Traditional African medication in the treatment of HIV. Lancet 2005; 5: 465-467.
(7.) Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355: 134-138.
(8.) Bartlett JG, Gallant JE. The 2007 Medical Management of HIV Infection. Baltimore, Md: Johns Hopkins Medicine Health Publishing Business Group, 2007: 192-193.
(9.) Kosel BW, Aweeka FT, Benowitz NL, et al. The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS 2002; 16: 543-550.
(10.) Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002; 34: 234-238.
(11.) Medlineplus. Herbs, Supplements and HIV. http://projectinform.org/fs/herbs_g.html (accessed 22 February 2006).
(12.) De Smet PAGM. Herbal remedies. N Engl J Med 2002; 347; 25: 2046-2076.
(13.) Piscitelli SC, Gallicano KD. Interactions among drugs for HIV and opportunistic infections. N Engl J Med 2001; 344: 984-996.
(14.) Kubukeli PS. Traditional healing practice using medicinal herbs. Lancet 2000; 354: SIV24.
(15.) Nyika A. Ethical and regulatory issues surrounding African traditional medicine in the context of HIV/AIDS. In: Nyika A. Developing World Bioethics. Oxford: Blackwell, 2006: 1-9.
THE BASIC APPROACH TO PROVIDING NUTRITION TO THE HIV-INFECTED
* Assess whether nutritional support is required
** History, weight, height, body mass index (BMI) and mid-upper arm circumference (MUAC) and examination. Laboratory tests, e.g. haemoglobin, serum albumin, fasting lipids, etc., where indicated.
** Where possible, work as a team so as to ensure that the patient's nutritional needs are recognised and acted upon: doctor, nurse, dietician, social worker, patient/parent/caregiver.
* Set goals
** Improvement in weight and length or height (children).
** Infants: exclusive breastfeeding for 6 months or formula feeds where this satisfies the UNAIDS/WHO/ UNICEF 'AFASS' criteria, viz. acceptable, feasible, affordable, sustainable and safe. If the infant tests HIV positive, breastfeeding is continued. Exclusive breastfeeding is continued where the mother cannot meet the AFASS criteria.
** Maternal antiretroviral therapy (ART) is continued during the breastfeeding period (and beyond, where appropriate for the control of the mother's infection).
* Advise the patient or caregiver (parent) on how to achieve good nutritional goals.
** What are the patient's current eating habits? How and what does the child/patient eat?
** What food is available? What food is eaten in the home: frequency, quantity, quality?
** Who looks after the infected patient? What practical support is available?
** Aim at a minimum of three balanced and varied meals a day.
** Aim at a minimum of two to three portions of fresh vegetables and/or fruit per day.
* Does the patient need nutritional help? Select the appropriate form of support needed
** Immediate support and action
*** Nutritional supplements
*** Therapeutic feeds
*** Family food support
*** Social support programmes: School feeding programmes, child grants, disability grants, referral to non-governmental organisation (NGO) programmes and faith-based groups in the community.
** Long-term recovery action
*** Poverty relief and political/social intervention
*** Access to ART and approved HIV management programmes
*** Prevention and rapid control of opportunistic disease, particularly tuberculosis (TB), diarrhoeal illnesses in children and upper respiratory tract disease. Support for appropriate vaccination programmes.
Members of the Nutritional Focus Group: D C Spencer (Chair), C Harman, C Botha, C Egbers, A Caradas, E Hefer, T J Dlamini, B Ndzungu, C Julsing, Z Makasi, F Venter, M Yssel, T Robinson.
INCREASING ENERGY INTAKE (3)
* Asymptomatic HIV-infected adult or child: increase energy intake by 10%. Give extra food.
* During and immediately after an opportunistic disease such as TB, gastroenteritis and chronic lung disease, the body's total energy expenditure increases by 20-30%. Both food-based and nutritional supplements can be used to meet these extra needs.
* Severe malnutrition increases basic energy needs by 50-100% in children. These needs require therapeutic feeding. This is best managed in conjunction with a dietician who will advise and assist in calculating the amounts of food/special feed required.
INTERPRETATIONAL DILEMMAS WITH REGARD TO MICRONUTRIENT STUDIES AND HIV (10,11)
* Too few randomised controlled trials (RCTs)
* Studies frequently not standardised with regard to micronutrient amounts or composition
* Studies seldom control for the acute-phase response or the effect of intercurrent inflammatory conditions (e.g. infections)
* Studies seldom control for the basic daily intake of micronutrients in food/diet
* Insufficient regard for the effect of interactions between the varying doses of different micronutrients in an individual supplement
MICRONUTRIENTS IN THE MANAGEMENT OF THE HIV-INFECTED
* Malnourished HIV-infected adults and children must be assured of food with or without daily supplements.
* Where micronutrient requirements cannot be met adequately with food, give supplements.
* If micronutrients are needed, daily individual supplementation at not more than 1-2 times the RDA is permissible.
* Malnutrition is common in the developing world. Micronutrient supplementation is therefore likely to be beneficial to most of Africa's HIV-infected people.
* The micronutrient fortification of food is essential in developing regions. Countries and their food industries must be made aware and held accountable.
* Vitamin A supplementation of all children aged under 5 years is mandatory in developing regions. See text for dosing details. Note that high doses of vitamin A have been associated with an increased risk of HIV disease progression in adults. High doses should be avoided.
* Supplementation with zinc improves the clinical outcome in HIV-infected children with diarrhoea. A daily dose of 10 mg for 2 weeks in children below the age of 12 and 20 mg for those above this age is recommended. Severely malnourished children with diarrhoea should continue with zinc supplementation for 2-4 weeks.
AFASS: ACCEPTABLE, FEASIBLE, AFFORDABLE, SUSTAINABLE AND SAFE
This means that the mother does not see any barrier to formula feeding. In some cultures, refusal to breastfeed may result in stigma, discrimination and rejection on cultural or social grounds or the tacit acknowledgement of being HIV positive. Mothers who choose to formula feed must be able to do so without fear of repercussions.
Formula feeding requires adequate time, knowledge, skill and resources to feed an infant up to 12 times a day. The mother will need to mix formula adequately within the constraints of her work and family schedule.
The mother and her family must be in a position to purchase and prepare formula feeds. This requires sufficient money to cover fuel costs and that of clean water, soap and the equipment needed (sterile bottles, cleaning agents, etc.). There must be no compromise of the family's finances with regard to their nutrition and medical needs.
There must be a continuous, uninterrupted and dependable system that ensures that the infant always has milk. Where the mother is absent, another caregiver must be able to prepare the formula feed reliably.
Replacement/formula feed must always be correctly, hygienically handled and stored. In addition, sufficient quantities must always be available for the child.
(World Health Organization (43))
IS EXCLUSIVE BREASTFEEDING POSSIBLE IN SOUTH AFRICA?
Yes, but it requires the support of lactating mothers. Pre- and postnatal counselling is essential to ensure the mother's attempts at breastfeeding are successful. Counselling would include guidance on the following:
* Good lactation management (early initiation, attachment, positioning, frequent feeds, learning to express) to avoid mastitis, cracked nipples, etc.
* Condom use during lactation period
* Avoidance of feeding from breasts with cracked, bleeding nipples or abscesses (express and discard milk from affected side and continue feeding from unaffected side)
* Prompt treatment of infant oral thrush
* Heat treatment of expressed breastmilk
* The promotion of exclusive breastfeeding for up to 6 months
* Nutritional support for breastfeeding mothers irrespective of CD4 count
In the context of preventing mother-to-child HIV transmission, health workers need to be 'agents of change'.
* Mother-to-child transmission is preventable.
* There is no evidence that micronutrients prevent HIV transmission.
* Where malnutrition and HIV infection coexist, providing food and correcting specific nutritional deficiencies remains the appropriate response.
* Antiretroviral drugs are the only consistent means to reduce maternal viral load and reduce perinatal HIV transmission.
* Exclusive breastfeeding has been shown to reduce mother-to-child transmission.
* Exclusive breastfeeding should be encouraged for the first 6 months of life.
THE WHO DEFINITION OF SEVERE ACUTE MALNUTRITION (SAM) (10)
Any of the following criteria:
* Weight-for-length/height <3 Z-scores below reference range (or)
* Bilateral pitting oedema (or)
* Severe visible wasting (or)
* Mid-upper arm circumference (MUAC) [less than or equal to] 110 mm for children 6 months - 5 years.
NB: The proposed WHO Draft Malnutrition MUAC Guideline range for the following ages:
Age 6 - 9 years <135 mm
Age 10 - 14 years <160 mm. *
* Source: Nigel Rollins, Durban, KwaZulu-Natal, August 2007.
D C Spencer, C Harman, C Botha, for the Nutritional Focus Group of the SA
Reviewers : N Rollins, D Labadarios, M Visser
TABLE 3.1. NUTRITIONAL AND 'COMMONSENSE' APPROACHES TO SYMPTOM CONTROL (9) Symptom Medical diagnosis Medical treatment 1. Anorexia, 1. Systemic disease, 1. Treat the underlying loss of e.g. TB, lymphoma condition appetite or 2. Local oral disease, 2.Cyproheptadine poor appetite e.g. thrush, gingivitis, (Periactin) 4 mg qd po ulcers x 7 - 10 days. 3. Medication: ARVs, TB 3. Steroids to be used drugs, antibiotics and with caution and under chemotherapy supervision: prednisone 4. Depression, fear and 0.5 - 1.0 mg/kg/d x anxiety 5 - 10 d 5. Malnutrition with 4. ARVs: control the apathy and chronic underlying viral helminth infestation disease 2. Painful 1. Local causes are 1. Treat the underlying mouth and usual viral infections: condition discomfort 'flu and the common 2. Topical anaesthetic with cold, herpes stomatitis ointments or spray swallowing (HSV), cyto-megalovirus before meals, e.g. (CMV), HIV ulcers, amethecaine gel bacterial infection: 3. Topical steroid gingivitis and tonsilli- ointment for aphthous tis; Fungi: candidiasis sores, e.g. kenolog in 2. Immune: aphthous orabase ulcers 4. Topical antifungal 3. Tumour: carcinoma, lozenges or cream for lymphoma angular cheilitis, e.g. amphotericin B, nysta- tin gel or solution 3. Fever: body Often a sign of 1. Treat the underlying temperature systemic disease condition persistently 1. Infection: malaria, 2. Paracetamol 250 - >37.4[degrees]C TB, invasive bacterial 500 mg 6-hrly po (prn) dis., pneumonia, 3. Aspirin 300 mg 6- bacteraemia hrly po (prn), non- 2. Tumour: lymphoma, steroidal anti-inflam. dissem. Kaposis's drugs (NSAID, e.g. 3. Toxins and drugs: ibuprofen) Aspirin is ARVs, antibiotics, e.g. not used in children co-trimoxazole, penicillin 4. Immune: immune re- constitution syndrome (IRIS), allergy 4. Nausea and 1. Local gastrointes- 1. Diagnose and treat vomiting tinal tract disease: the underlying cause oesophageal lesions, 2. Anti-nauseants, e.g. peptic ulcer and metoclopromide 10 mg gastritis and 8-hrly before meals pancreatitis (prn) 2. Systemic infections 3. Remove the offending and medical conditions cause 3. Medication and toxins: ARVs--zidovudine and ritonavir, TB drugs, antibiotics esp. metro- nidazole, alcohol and recreational drugs, traditional drugs and potions 4. Metabolic disorders: uncontrolled diabetes, lactic acidosis, renal and liver disease 5. Fear and anxiety 5. Diarrhoea 1. Local GIT disease, 1. Diagnose and treat Defined as a HIV enteropathy, Slim the underlying cause minimum of disease and opportunist- 2. Immodium 1 - 2 tabs three soft, un- is enteric infections, po daily or bid in formed stools e.g. cryptosporidiosis adults. Immodium is per day 2. Systemic diseases, NOT given to children e.g. TB, lymphoma 3. Codeine phosphate 3. Drugs and toxins, 10 - 30 ml daily or bid e.g. ARVs: didanosine, po in adults. Codeine ritonavir, lopinavir, is NOT given to nelfinavir; antibiotics children. and antibiotic- 4. Oral rehydration associated diarrhoea (C. solution (children): 1 dificile enterocolitis), litre boiled water, and alcohol; traditional 8 teaspoons sugar, 1.2 medicines and herbs teaspoon salt 5. Zinc (allovera) (children): 10 mg daily 4. Metabolic: uncontrol- po x 2 wks in those <6 led diabetes mellitus, mo. age, or 20 mg daily hyperthyroidism po x 2 wks in those >6 mo. of age 6. Continue feeding the child 7. Vitamin A: dose as per age in children <5 yrs 8. Refer the child to the clinic if either weight loss is present or diarrhoea continues for >14 d Symptom Dietary and supportive treatments 1. Anorexia, Small but frequent meals loss of and favourite foods, appetite or liquids, soft foods poor appetite rather than a full meal: high-energy and high- protein drinks and foods. Avoid foods with a strong smell, e.g. fish, cheese and eggs. Snack often, and keep snacks handy e.g. car, hand-bag. Drink frequently. Emotional support and counselling. 2. Painful Avoid acidic foods, e.g. mouth and citrus fruit, tomatoes, discomfort spicy foods. Drink throgh with swallowing a straw. Eat foods at room temp. or well cooled. Suggest thick and smooth foods such as puddings, porridge, mashed potatoes, beans. Clear fluids are more easily aspirated-- sit upright when eating and tilt head slightly back. Rinse mouth with boiled, warm salt water after eating. 3. Fever: body Encourage rest. Cool bath temperature and/or tepid sponging. persistently Fan and remove warm >37.4[degrees]C bedding, Drink lots of fluid. Take high-energy foods, e.g. added oil, margarine, sugar, to enhance caloric value. 4. Nausea and Encourage eating even if vomiting only small quantities can be taken. Avoid an empty stomach--this will increase the nausea. Small but regular meals of bland food such as soups, porridge, mashed bananas. Dry toast and cream crackers are helpful. Ginger may ease nausea: ginger ale. Herbal teas and lemon juice in hot water. Drink plenty of fluids but not during the meal as this will increase the sense of bloatedness. Avoid spicy and fatty and strong-smelling foods. Avoid fizzy drinks and caffeine. 5. Diarrhoea Lots of fluids such as Defined as a soup, diluted juices, minimum of boiled water, herbal three soft, un- teas. Avoid citrus fruit formed stools or citrus drinks e.g. per day oranges, lemons. Suggest bananas, rice, peeled apples, white toast, oats and lentils (strained), maas and yoghurt. Fruit juices that are accept- able: apple, pear and grape. Leave off bran and fibre from diet: no whole-grain breads, no wheat-bix or high-fibre cereals. No fried or fatty foods. Avoid caffeine and alcohol. TABLE 3.II. VITAMINS AND IMMUNE/BIOLOGICAL INTERACTIONS Vitamin Source Vitamin A, Full-cream milk when fortified carotenoids Cheese, butter, red palm oil Fish oils, eggs, liver, carrots, mangoes, papaya, pumpkin, Green leafy vegetables, sweet potatoes Vitamin E Green leafy vegetables, liver, vegetable oils, wheat germ, whole-grain products, butter, peanuts, milk, nuts and seeds, egg yolk and fats Vitamin C Citrus fruit: baobab, guava, oranges and lemons. Cabbage, green leaves, tomatoes, yams, peppers, cooking plantains, fresh milk Vitamin Green leafy vegetables, liver, [B.sub.12] meat cyanocobalamin Vitamin Described immune and biological effects Vitamin A, Enhanced phagocytic activity, which is reduced carotenoids in vitamin A deficiency. Important in vision, the differentiation of cells, cellular recognition, growth, bone development and reproduction. Vitamin E Promotes phagocytosis, adherence and chemotaxis. Supplementation protects natural killer (NK) cell and suppresses the production of toxic oxygen radicals. The most important lipid-soluble antioxidant in cell membranes. Vitamin C Supplementation enhances NK cell activity, phagocytosis, adherence and chemotaxis. Acts as an antioxidant within the cell. NB: The activity of vitamin C is lost when food is cut, heated or left standing after cooking. Vitamin Deficiency leads to decreased bacterial killing. [B.sub.12] A coenzyme that is needed for the maintenance cyanocobalamin of neural tissue and for folate-dependent red cell synthesis. TABLE 3.III. TRACE ELEMENTS AND IMMUNE/BIOLOGICAL INTERACTIONS Trace element Source Selenium Meat, eggs, seafood, whole grains and plants provided their soil is rich in selenium Zinc Meat, fish, poultry, shellfish, whole-grain cereals, legumes, peanuts, milk and cheese Iron Liver, chicken, beef, egg yolk Beans, nuts, green leafy vegetables, fortified cereals Trace element Described immune/biological action Selenium An antioxidant that is active within the glutathione peroxidase enzyme system. Supplementation increases macrophage phagocytic and cytotoxic activity. Deficiency leads to reduced antibody production. Zinc Zinc is a cofactor in enzymes systems and is active in cell growth. It is an antioxidant. Zinc is necessary to thymus development, the production of superoxide dismutase. Supplementation results in the production of cytokines and the major histocompatibility complex (MHC) class 1 proteins. Iron Is a pro-oxidant. Iron-containing cellular components, e.g. haemoglobin, myoglobin, permit oxygen delivery to tissues. Deficiency appears to inhibit TH-1 cellular immune activity and reduce neutrophil function. TABLE 4.I. GENERALLY ACCEPTABLE INCREMENTS OFWEIGHT DURING PREGNANCY (51) Body mass index (BMI), pre-pregnancy (kg/[m.sup.2]) Total weight gain (kg) Underweight (<20) 12.5 - 18 kg Normal (20 - 25) 11.5 - 16 kg Overweight (25 - 30) 7 - 1.5 kg Obese (>30) [less than or equal to] 7 kg TABLE 4.II. RISK FACTORS FOR THE TRANSMISSION OF HIV THROUGH BREASTFEEDING (41) Strong evidence High plasma viral load Advanced disease/ low CD4 count Breast pathology--mastitis, abscesses, cracked bleeding nipples Primary infection/new infection: high plasma viral load Prolonged duration of breastfeeding (>6 mo.) Non-exclusive breastfeeding, mixed feeding and oral lesions (55) Limited evidence High breastmilk viral load Sub-clinical mastitis as evidenced by increased breastmilk sodium levels Low maternal levels of vitamins B, C, E TABLE 4.III. WORLD HEALTH ORGANIZATION 2006 BREASTFEEDING RECOMMENDATIONS (43) * The most appropriate infant feeding option will depend upon the mother's circumstances but ought to consider local health care services, counselling and practical support available to the mother. * Exclusive breastfeeding is recommended for HIV-infected women for the first 6 months of life unless replacement feeding is acceptable, feasible, affordable, sustainable and safe (AFASS criteria). * At 6 months, if replacement feeding still does not satisfy AFASS criteria, breastfeeding must continue with the addition of complementary feeds. The mother and baby must be regularly assessed. All breastfeeding must stop once a nutritionally adequate and safe diet without breastmilk can be provided. * Whatever the decision, health services must continue to follow up and support women and HIV-exposed infants offering counselling and assistance when feeding decisions are being reconsidered. * Breastfeeding mothers and infants who are known to be HIV-positive should be encouraged to continue to breastfeed. * Governments and other stakeholders are encouraged to revitalise breastfeeding protection, promotion and support. They are asked to actively support women who choose to exclusively breastfeed and to ensure that replacement feeding is safer for women who choose that option. * National health programmes are asked to provide all HIV-exposed infants and their mothers with a total package of interventions that will promote survival and the prevention of transmission. Those women in the antenatal clinic who test HIV negative ought also to have access to primary prevention programmes for themselves and their infant. * Governments are urged to ensure that all the above interventions, including those dealing with exclusive breastfeeding, are available before distribution of free commercial infant formula is considered. * Governments and donors are requested to increase their commitment and resources to ensure the implementation of the Global Strategy for Infant and Young Child Feeding and the UN HIV and Infant Feeding Framework for Priority Action in order to prevent postnatal HIV transmission, improve HIV-free survival and achieve relevant UNGASS goals. TABLE 4.IV. AMOUNTS FOR INFANT FEEDING UNTIL 6 MONTHS OF AGES No. of tins required for 1 Milk feed infant per Previously No. of month (varies boiled No. of feeds per with the Age of infant water scoops 24 hours individual) 1 - 2 wks 100 ml 4 6 7 tins 3 - 4 wks 125 ml 5 5 7 tins 2nd mo. 150 ml 6 5 9 tins 3 - 4 mo. 175 ml 7 5 10 tins 5 - 6 mo. 200 ml 8 4 9 tins TABLE 5.I. WEIGHT LOSS IN HIV-INFECTED CHILDREN--CAUSES AND RELATIONSHIPS (31) Increased energy requirements Energy needs increase by 10% from time of acquiring virus Energy needs increase by 20 - 30% during and after illness Energy needs may increase to 50 - 100% in severely malnourished children NB. Protein requirements remain at 12 - 15% of total energy intake provided diet is well balanced Inadequate energy intake Anorexia and poor dietary intake: oral candidiasis, gingivitis, oral sores, oesophageal candidiasis and dysphagia, loss of taste, insufficient food, poverty Opportunistic infections and cancers: chronic lung disease (lymphoid interstitial pneumonitis, LIP), chronic diarrhoea, tuberculosis, recurrent respiratory infections, lymphoma Advanced HIV infection and untreated, end-stage HIV infection TABLE 5.II. ADEQUATE CALCIUM INTAKE * Estimated adequate daily Age or 'life-stage group calcium intake Children 1 - 3 yrs 500 mg daily Children 4 - 8 yrs 800 mg daily Adolescents and young adults 9 - 18 yrs 1 300 mg daily Men and women 19 - 50 yrs 1 000 mg daily Men and women >51 yrs 1 200 mg daily * Lindsay and Cosman, (90) adapted from the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine, Washington, DC, 1997, National Academy Press. Note that for pregnancy and lactation needs are the same as for non-pregnant women. TABLE 6.I. FOOD INTERACTIONS AND THE ARVs (1) Food effect and inter- ARV medication actions withother drugs Dietary recommendation Nucleoside and nucleotide reverse transcriptase inhibitors (NRTI/NtRTIs) Abacavir (ABC, No effect. Alcohol Can be taken without Ziagen) 300 mg bd increases the area regard to meals. po (Trisivir: ZDV under the curve (AUC) Avoid alcohol. + 3TC + ABC; by 41%. Kivexa: ABC + 3TC) Didanosine (doll, Food decreases absorp- Take on an empty Videx; Videx EC) tion: approx 55% reduc- stomach at least 30 400 mg/d po if tion in AUC. Avoid mag- minutes before a meal weight >60 kg or nesium and aluminum or 2 hours after. Take 250 mg if <60 kg containing antacids: only with water. these decrease Alcohol increases absorption. toxicity: avoid. Emtricitabine (FTC) Food has little effect Can be taken without 200 mg daily po on absorption or regard to meals. Avoid (Truvada, TVD: TDF metabolism. alcohol. If on Atripla + FTC; Atripla: or Truvada, take with TDF + FTC + EFV) a light meal as food increases the absorp- tion of tenofovir. Lamivudine (3TC, Food has little effect Can be taken without Epivir) 150 mg bd on absorption or regard to meals. But po (Combivir: ZDV metabolism. Combivir is taken on + 3TC; Kivexa: an empty stomach. ABC + 3TC; Avoid alcohol. Triomune, Stalinev: d4T + 3TC + NVP) Stavudine (d4T, Food has little effect Can be taken without Zerit) 30 mg bd po on absorption or regard to meals. Avoid irrespective of metabolism. alcohol weight (Triomune, Stalinev: d4T + 3TC + NVP) Tenofovir (TDF, Administration with a Take with food. Viread) 300 mg/d high-fat meal increases po (Truvada: TDF + AUC by 40%. FTC, Atripla: TDF + FTC + EFV) Zalcitabine (ddC, Food has little effect Can be taken without Hivid) 0.75 mg on absorption. Avoid regard to meals. Avoid 8-hrly po antacids containing alcohol. magnesium or aluminum. Do not take together with metoclopromide: decreases the AUC. Zidovudine (AZT, AUC decreased by 25 - Preferably take on an ZDV, Retrovir) 300 50% with food. empty stomach. Other- mg bd po (Combivir: wise, a low-fat meal. ZDV + 3TC; Avoid alcohol. Trisivir: ZDV + 3TC + ABC) Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz (EFV, Low-fat meals improve Can be taken without Stocrin, Sustiva) tolerability: high-fat regard to meals. Avoid 600 mg/d (nocte) meals increase AUC by a high-fat meal. po (Truvada and 50%. Care with drugs Alcohol may increase Atripla) that induce or inhibit unpleasant side- cytochrome P-450 effects. (CYP450) activity. Avoid St John's Wort. Nevirapine (NVP, Absorption not affected Can be taken with Viramune) 200 mg by food. Care with food. Avoid alcohol. bd po (Triomune drugs that induce or and Stalinev) inhibit CYP450 activity. Avoid St John's Wort. Protease inhibitors (Pls) Amprenavir (APV, High-fat diet decreases Can be taken without Agenerase) 1 200 absorption and regard to meals but mg bid po decreases AUC. Avoid avoid a high-fat meal. (Fosamprenavir) grapefruit juice. Increase daily fluid intake. Avoid vitamin E supplements, antacids and St John's Wort. Atazanavir (ATZ, Absorptior is enhanced Given with meals. Reyataz) 400 mg with food. daily or 300 mg + ritonavir 100 mg (boosted) daily po Indinavir (IDV, Presence of high-fat, Taken on an empty Crixivan) 800 mg 8 high-protein meal stomach at least 1 hourly po or 800 decreases serum levels hour before or 2 hours mg bid + ritonavir by 84% and AUC by 77%. after a meal unless 100 mg (boosted) Drink 2 litres of fluid taken with ritonavir. bd po or 400 mg bd daily to avoid renal If taken with + 400 mg ritonavir stones. Avoid grape- ritonavir (i.e. (boosted) bd po fruit juice and boosted), can be taken St John's Wort and take with a light low-fat care with other drugs meal. (inducers and inhibi- tors) that use the CYP450 system. Lopinavir (LPV/r: Absorption improved Take with meals of a Kaletra capsules: with a high-fat meal. high fat content. lopinavir 133.3 mg Interacts with medica- Kaletra is stored in + ritonavir 33.3 tion that use CYP450 a refrigerator. Aluvia mg), 3 capsules bd system. Avoid St John's does not require po; Aluvia tablets: Wort. refrigeration. LPV + RTV, 2 tablets bd po Nelfinavir (NLF, AUC and plasma concen- Take with meals or a Viracept) 750 mg trations increase after light snack that td or 1 250 mg bd a meal. Increase fluid includes food of high po intake. Avoid acidic protein content to foods and St John's enhance absorption. Wort. Diarrhoea, a common side-effect, may be improved with lactose- free dairy products. Ritonavir (RTV, Absorption increased Take with a meal. Norvir) 600 mg bd with food. Multiple Store in the po or in 'boosted' drug-drug interactions: refrigerator. combinations with uses CYP450 enzyme other Pls system. Avoid St John's Wort. Saquinavir (SQV, Absorption increased Take with a meal: high Invirase, the hard- with food and with fat and high calorie gel formulation) grapefruit juice. content enhances 600 mg td or in Latter inhibits intes- absorption. Avoid combination with tinal CYP3A4 system. alcohol. ritonavir e.g. SQV Avoid St John's Wort. 400 mg/RTV 400 mg bd po Tipranavir (TPV, Utilises the CYP450 Should be taken Aptivus) 500 mg + system: care needs to together with food: ritonavir 200 mg be taken with the co- fewer gastric side- bd po administration of drugs effects. that activate the P- glycoprotein drug transport (efflux) mechanism and CYP enzyme systems.
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|Title Annotation:||GUIDELINES; human immunodeficiency virus; Acquired immune deficiency syndrome|
|Author:||Spencer, D.C.; Harman, C.; Botha, C.|
|Publication:||Southern African Journal of HIV Medicine|
|Date:||Jun 22, 2008|
|Previous Article:||HIV infection and the kidney.|
|Next Article:||Antiretroviral therapy in adults: January 2008.|
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