Disease progression unrelated to passive environmental tobacco smoke exposure in HIV-infected children.Background
Cigarette smoking has been associated with increased morbidity and mortality Morbidity and Mortality can refer to:
Human immunodeficiency virus (HIV)
A transmissible retrovirus that causes AIDS in humans. (HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. )-infected adults. [1,2] In the Strategies for Management of Antiretroviral Therapy Clinical Trial, 40 x 5% of HIV-infected subjects were current smokers and 24 x 8% were former smokers.  The mortality of these individuals was higher in current smokers (hazard ratio (HR)=2 x 4; p<0 x 001) and there were more serious illnesses (major cardiovascular disease (HR=2 x 0; p=0 x 002), non-AIDS cancer (HR=1 x 8; P=0 x 008), and bacterial pneumonia (HR=2 x 3; p<0 x 001)), in smokers. 
In addition to the risks of cigarette smoking it seems that the prevalence of smoking is higher in HIV-infected individuals. This has been clearly shown for African HIV-infected individuals. [3,4]
Increased morbidity in smoking HIV-infected adults may take many forms. Importantly smoking increases the risk for secondary infection, including tuberculosis,  cardiovascular disease [1,6] and malignancy. [1,7]
Studies in adults have revealed that smokers on highly active anti-retroviral therapy (HAART) had poorer viral responses (HR=0 x 79; 95% confidence interval (CI)=0 x 67-0 x 93) and poorer immunologic responses (HR=0 x 85; 95%CI=0 x 73-0 x 99).  A greater risk of virological rebound (HR=1 x 39; 95%CI=1 x 06-1 x 69) and more frequent immunologic failure (HR=152; 95%CI=1 x 18-1 x 96) were also observed among smokers. There was a higher risk of death (HR=1 x 53; 95%CI=1 x 08-2 x 19) and a higher risk of developing AIDS (HR=1 x 36; 95%CI=1 x 07-1 x 72), but no significant difference between smokers and non-smokers in the risk of death due to AIDS. These authors concluded that 'some of the benefits provided by HAART are negated in cigarette smokers'. 
These findings may relate to research demonstrating that chronic exposure of mice and rats to cigarette smoke or nicotine inhibits T-cell responsiveness, which may account for the decreased antibody response to T-cell dependent antigens seen in these animals. 
Other studies have confirmed an increased risk of smoking adults to infections. Current smokers were more likely than never smokers to develop bacterial pneumonia (HR=1 x 57; 95%CI=1 x 14-2 x 15; p=0 x 006), oral candidiasis candidiasis (kăn'dĭdī`əsĭs), infection of the mucous membranes caused by the fungus Candida albicans. Other terms for candidiasis are yeast infection, moniliasis (after a former name of the fungal genus), and thrush, the (HR=1 x 37; 95%CI=1 x 16-1 x 62; p=0 x 0002).  The AIDS dementia complex AIDS dementia complex
The neurological disease complex that is sometimes experienced by AIDS patients, caused by neuron injury and death and characterized by cognitive impairment. is also more likely in smoking HIV-infected adults (HR=1 x 80; 95%CI=1 x 11-2 x 90; p=0 x 02). 
These increased risks have led authors to call for incorporating advice on smoking cessation into HIV education programs and consultations. 
The natural progression of HIV in children differs from that of adults. Immaturity of the immune system leads to more rapid progression of HIV-related infection.  There are various factors that contribute to the rate of HIV progression in children. These include maternal viral load, genetic composition, immunological profile of the child and possibly some environmental factors. 
Despite a vast literature on the health effects of cigarette smoking on HIV-infected adults, there is no study demonstrating an effect of passive cigarette smoke exposure on the health of HIV-infected children.
The main objective of this research was to determine if passive environmental tobacco smoke (ETS) exposure is a risk factor for HIV progression and disease severity in children.
An observational, descriptive study of children attending the HIV Clinic at Tshwane District Hospital Previously known as Pretoria Academic Hospital, it is now a community hospital that deals in non-critical care. , Pretoria, South Africa during October 2007. A convenience sample of parents attending the clinic for routine follow-up of their children's disease was selected. Each attendee completed a questionnaire relating to their smoking habits and the HIV status of their children. Ethics approval was obtained from the Research Ethics Committee of the University of Pretoria and all subjects signed informed consent and assent where appropriate.
HIV infection was deemed to be present if HIV-enzyme linked immune-sorbent assay (ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.
n. ) was positive in children older than 18 months of age. Children younger than 18 months required both a positive HIV ELISA and positive HIV polymerase chain reaction (PCR PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) ).
The World Health Organization (WHO) HIV clinical staging  was used to determine HIV stage of disease.
The Architect (Abbott Diagnostics) and MODULAR E170 (Roche Diagnostics), fourth generation HIV ELISA assays (detecting both p24 antigen and HIV antibodies simultaneously), were used for HIV serology Serology
The division of biological science concerned with antigen-antibody reactions in serum. It properly encompasses any of these reactions, but is often used in a limited sense to denote laboratory diagnostic tests, especially for syphilis. . Qualitative HIV PCR was performed using Amplicor HIV-1 DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. assay, version 1 x 5 (Roche molecular systems). CD4 count measurements were performed on Epics instrument (Beckman Coulter Diagnostics) using a pan leukocyte leukocyte (l`kəsīt'): see blood.
or white blood cell or white corpuscle gating (PLG) method.
Stata 10 (eStataCorp LP, 4905 Lakeway Drive, College Station, Texas College Station is a city in Brazos County, Texas, situated in Central Texas. It is located in the heart of the Brazos Valley. The city is located within the most populated region of Texas, near to three of the 10 largest cities in the United States - Houston, Dallas, and San 77845 USA) was used for computations. The two-sample t test with equal variances was performed for analysis of continuous variables while the Fischer exact test or Pearson Chi-square test was performed for analysis of categorical variables.
Information was obtained from 127 accompanied HIV-infected children. Of these, 47 (37%) were living in households where adults smoke. There was not a significant difference in the mean age (at the time of the study) between ETS exposed and non-exposed children (4 x 6 months vs 4 x 9 months (p=0 x 66)). There was also not a significant difference for age of HIV diagnosis between ETS exposed and non-exposed children (p=0 x 50). 118 (93%) of the children were on HAART. At the time of the study the protocol for HAART was Stavudine, Lamivudine and Kaletra as first line therapy.
ETS exposed children had a 11% lower CD4 percentage than children who had no passive smoke exposure. This was not statistically significant (p=0 x 59) (Fig. 1).
There was not a significant relationship between cigarette smoke exposure and HIV-stage (p=0 x 70) (Table 1).
There was not a significant relationship between the number of cigarettes smoked daily by the caregivers and the CD4 count (p=0 x 9661), nor the HIV stage (p=0 x 4949), of the of the ETS exposed children.
Thirty two of the 127 children were hospitalized in the last month. This group included all of the children not on HAART and only 13 of the 32 children that were hospitalized in the last month had care-givers who smoked. The ETS and non-ETS groups did not differ with respect to hospitalization (OR=1 x 17; 95%CI=0 x 47-2 x 86; p=0 x 70) (Table 2).
The proportion of smokers amongst parents with secondary education does not differ significantly from those without secondary education (p=0 x 595; 38 x 2% vs 29 x 4%).
This is the first study reported of the effects of passive ETS exposure on the health of HIV-infected children.
The study reveals that rates of cigarette smoking are higher in parents of HIV-infected children than the South African national average.  This may support data available from other studies in Africa demonstrating that smoking was more common in HIV-infected adults. [3,4]
This study of 127 HIV-infected children attending an HIV treatment clinic did not reveal statistically significant differences in objective measures of HIV status (CD4 count and HIV stage) between children exposed to ETS and those not exposed. This is in contradistinction con·tra·dis·tinc·tion
Distinction by contrasting or opposing qualities.
contra·dis·tinc to most adult studies.
In addition there is no apparent effect of ETS exposure on clinical disease severity as indicated by need for hospitalization. ETS exposure has been linked to greater risk of asthma exacerbations in asthmatic children  and it seems unlikely that this is not true of disease exacerbations in HIV-infected children. Either the study sample was too small to draw meaningful conclusions or the diseases associated with HIV-infection are of such a nature to render the additional effects of ETS insignificant.
Since most children were on HAART the effect of this form of therapy in relation to ETS exposure could not be assessed. Only a much larger study group would enable teasing out of the effect of cigarette smoke exposure on HIV-infected children prior to commencement of HAART or the possible effect of ETS exposure on efficacy of HAART.
The small sample size may limit comparison in this study. In addition the range of age in these children would mask some of the consequences of increasing age on HIV progression in individual patients. A large age-stratified study would be useful.
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Conflict of Interest:
All authors disclose no financial and personal relationships with other people or organisations that could inappropriately influence (bias) this work.
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Robin J. Green (1) *, Piet J. Becker (2), Denise Labuschagne (1), Omolemo P. Kitchin (1), Refiloe Masekela (1)
(1) Division of Pediatric Pulmonology, University of Pretoria, South Africa
(2) Biostatistics Unit, South African Medical Research Council, South Africa
* Corresponding Author
Table 1: Smoking status of caregivers versus HIV-stage of children, frequency (%). * Smoking HIV Stage No Yes Total 1 8 (119) 2 (5-0) 10 (9-4) 2 7 (105) 5 (12-5) 12 (11-2) 3 38 (56 7) 23 (57-5) 61 (57-0) 4 14 (20 9) 10 (25-0) 24 (22-4) 67 (100) 40 (100) 107 (100) * Staging data unavailable on 20 children. Table 2: Smoking status of caregivers versus hospitalization of HIV-infected children, frequency (%) Hospitalization Yes No Total Smoking Yes 13 (27-1) 35 (72-9) 48 (100) No 19 (24-1) 60 (76-0) 79 (100) 32 (25-2) 95 (74-8)