Printer Friendly

Safety profile of antiretroviral therapy: an urgent need for monitoring.


The diminution of CD4 lymphocytes is the diagnostic characteristic of human immunodeficiency virus (HIV) infection. Since the discovery of the disease 35 years ago, the infection has become one of the greatest menaces for the modern civilization. [1] For the near future, HIV is like to be one of the most common chronic infectious diseases on the planet. [2] The estimated number of persons living with HIV worldwide in 2013 was 35 million. In the year 2013, 2.1 million people were newly infected with HIV and about 1.5 million people died from acquired immune deficiency syndrome (AIDS), mostly because of inadequate access to HIV prevention and treatment services. In 2013, an estimated 4.8 million people in Asia and the Pacific were living with HIV including the 350,000 people newly infected. Approximately, 250,000 people died from AIDS-related illnesses. There were almost 6% declined in new HIV infections from 2005 to 2013. [3] In Nepal, the estimated number of people living with HIV is about 39,000 while the prevalence rate in adults aged 15-49 is 0.2%. The HIV prevalence among the adults has not changed much over the last 5 years and has remained within the range of 0.2-0.3%. The mortality due to HIV in the year 2014 was around 2500, and the projected death in 2020 is 1266, due to an expected rise in antiretroviral therapy (ART). [4]

With the discovery of effective antiretroviral (ARV) agents, agent-specific toxicity pattern has emerged that require prudent ARV selection to minimize treatment-related morbidity and mortality. There are many individual drug toxicities and a number of class-specific or therapy-related toxicities, which warrant further discussion. Nucleoside reverse transcriptase inhibitors (NRTIs) have infrequently been associated with lactic acidosis, peripheral neuropathy, myopathy, and pancreatitis. Rashes and hepatitis are both recognized side effects of the non-NRTIs (NNRTIs) class although the incidence and severity of these complications appear greatest with nevirapine.[5-7] All ARV drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from class to drug class, and from patient to patient. A better understanding of the adverse effect of ARV agents is of interest not only for HIV specialist as they try to optimize therapy but also for other physician who care for HIV-positive patients.

Many drugs that are used in the management of HIV-related disease are unlicensed or are prescribed for an unlicensed indication. Comprehensive data, for example, on drug interactions or side effect, is therefore lacking. Hence, in this review, we aimed to highlight the adverse effects of ART and ways of monitoring these effects.


The predisposing factors for adverse drug reactions (ADRs) are age, [8,9] compliance, [10-12] type of drug used, [8,13-17] CD4 count, [3,14,18] pregnancy, [19] sex, [8,19-21] race, [21-23] osteonecrosis, [24,25] coinfections. [26-29] The different type of ADRs associated are hyperglycemic and diabetogenic, [30-32] adipogenic, [33-35] hyperlipidemia, [19,36,37] dyslipidemia, [38] spontaneous bleeding episodes, [39,40] dermatologic and sensitive reaction, [41-44] hepatic effect, [28,29,45-47] lactic acidosis and steatosis, [48-51] gastrointestinal symptoms, [6,15,19] teratogenic effect, [52] nervous system effect, [18,53-56] peripheral neuropathy, [56-58] hematologic effect, [59] immune reconstitution syndrome, [60,61] cardiovascular effect, [62] sulfonamide sensitivity, [63] renal and genitourinary effect, [44,64] respiratory effect, [65] and pancreatitis. [6]


It is known that the incidence of adverse reactions is high in the initial ART and tends to decrease in later stages when long-term reactions such as lipodystrophy, paresthesia, and neuromotor disorders may occur. [66] Prevalence of attributed adverse event was highest in three-class-ARV treatment than the single protease inhibitor (PI)-ARV treatment of PI-sparing. [66] Hepatotoxicity is a well-recognized side effect of PI therapy with over 50% of patients develop asymptomatic mild elevation of transaminases. In some series up to 10-20% developed severe hepatotoxicity with liver enzymes rising above five times the upper limit of normal. [28] The hepatotoxicity of this drug class varies with the specific drug, 30% of patient who are treatment with ritonavir show toxicity, but only 6-7% of those are initiated therapy with saquinavir, nelfinavir, or indinavir experienced severe hepatotoxicity. [28] The NNRTIs are also associated with transaminitis and hepatotoxicity. The rate was hepatotoxicity is 8.9% and 10.8%, respectively, in a patient receiving nevirapine and efavirenz. [38] Rash is a common adverse effect of the NNRTIs, particularly nevirapine. Approximately, 16% of patients taking this agent experience a mild to moderate maculopapular rash with or without pruritus on the trunk, face, and extremities within the first 6 weeks on therapy. [38]

A degree of insulin resistance is also present and this lead to the development of Type 2 diabetes in about 7% of cases with a further 16% having impaired glucose tolerance. [67] The overall prevalence at least one physical abnormality related to lipodystrophy has been estimated about 50% after more than a year of ART. The prevalence of lipodystrophy increases progressively with duration of use so that 50% of the subjects are recognizable affected after 10 months use of agent. [33] The incidence of NRTI-associated lactic acidosis is 1.3/ 1000 person-year. [68] The risk of liver enzyme elevation among patients with chronic hepatitis B or C was, respectively, 2.77- or 2.47-fold greater after initiation of PI-containing regimen than among patients without evidence of viral hepatitis. [38,69] New-onset diabetes mellitus, clinically similar to Type II diabetes, affects a small proportion (1-6%) of infected patient treated with PI-based ARV regimens. [30,38] Osteonecrosis occurs only rarely in HIV patient. For example in one series, six cases occurred among 508 HIV patients. [70] The nucleoside analog abacavir causes a hypersensitivity syndrome in 3-5% of patients. [71,72]


The clinical trials of drug therapy, particularly those conducted before drug licensing are typically designed to gather detailed adverse event data. They are typically conducted in relatively well-controlled settings in regard to concomitant drug therapy and other medical management, with sample sizes usually in the hundreds. The population may also be relatively homogeneous typically with a large proportion men, nonminority/ethnic group, and noninjecting drug users. This makes it more difficult to assess comparative rates of adverse events by demographic characteristics of the patients. [14] Most of the studies on adverse effect have been conducted in developed countries where disease prevalence, access to medicine, drug use patterns, and drug management systems differ markedly from those of developing countries. [73] People have been using the oldest anti-HIV drug for more than a decade, but it is still not clear what effect may develop when people take highly active ART (HAART) over the course of most of the patient's lifetimes. Because many of the anti-HIV drugs were given rapid Food and Drug Administration approval, they have not benefited from years-long clinical trials to reveal uncommon or long-term side effects. Adverse reactions have been recorded anecdotally and in randomized clinical trial. [74]


In general, there are three major methods of monitoring.

Cohort event monitoring

It is often referred to as prescription event monitoring, but this terminology is inappropriate where individual prescriptions with subsequent dispensing are not part of the process. The cohort needs to be as complete and as representative as possible. Decisions will be required on how to select patients. Two options are available. The first is to enroll all patients in selected, representative regions until the number of patients in the cohort reaches the target figure. The second is a method of systematically sampling patients from the whole country. Cohort event monitoring is more labor intensive and more costly, and it is new to health professionals and pharmacovigilance centers.

Spontaneous reporting

It is an unsolicited communication by health-care professionals or consumers that describe one or more ADRs in a patient who was given one or more medical products, and that does not derive from a study or any organized data collection scheme. Spontaneous reports play a major role in the identification of safety signals, once a medicine is marketed. It can also provide important information on at-risk groups, risk factors (to a limited degree), and clinical features of known serious ADRs. Spontaneous reporting is dependent on encouraging clinicians and other health professionals to report details of suspected adverse reactions in patients on ARV treatment. Underreporting is a serious problem with this method, but reporting can be intensified in selected units such as hospitals.

Special phase IV studies

Discussion to date has indicated the need to establish pregnancy registers, monitor for specific toxicities, and monitor special populations such as children. These cannot be accomplished as an integral part of a spontaneous reporting program, and special studies would therefore be needed. However, adequate data in these important areas should be recorded in the normal course of events when using cohort event monitoring and special studies should be unnecessary. If special studies are to be undertaken, then the same principles will apply as outlined for cohort monitoring. Special forms would need to be designed to provide the information needed, and advice and training given on what is required and the appropriate data flow.


The monitoring program will help to:

* Identify signals of previously unidentified adverse reactions to medicines

* Quickly identify events that are likely to affect adherence to treatment; determine their rates and the risk factors that make these events more likely. Self-reported adverse effects can act as major determinants of ART adherence. [75] A more holistic approach to treatment regimen and adapting it to patient daily routines might improve better adherence [76]

* Estimate rates of events so that risk can be measured and the safety of medicines can be compared to make informed choices and to clearly identify risk factors to clearly identify risk factors

* Determine safety in pregnancy

* Determine safety in children

* Monitor for specific toxicities to establish rates, risk factors and to characterize the reactions.


There are numerous options and recommendations [77-79] to formulate the HAART regimens. However, the pioneer consideration is to ensure selection of ARV agents to which the virus is susceptible. Then, adherence and minimizing drug toxicity should be considered. The cardiovascular risk profiles should be assessed for each patient and specific comorbidities should be taken into consideration. Thus, ART is becoming not only increasing effective but also increasing complex. There are many adverse effects of the therapy may cause symptoms affecting a variety of organ system. To optimize the treatment health professionals should focus on preventing adverse effect of ARV agents.

DOI: 10.4103/2045-080X.181036


Authors would like to acknowledge Raju Paudel MD, DM (Neurology), Consultant Neurologist, Grande Hospital, Kathmandu, Nepal and Dr. Mukhyaprana Prabhu, Professor, Department of Medicine, Kasturba Medical College, Manipal, India, for reviewing the manuscript and recommending necessary modifications.

Financial support and sponsorship Nil.

Conflicts of interest

There are no conflicts of interest.


[1.] Raffanti S, Haas DW. Antimicrobial agents (continued) antiretroviral agent. In: Limbird LE, Hardman JE, Gilman AF, editors. Goodman and Gilman's the Pharmacological Basis of Therapeutics. New York: McGraw-Hill; 2001. p. 1349.

[2.] Flexner C. HIV drug development: The next 25 years. Nat Rev Drug Discov 2007; 6:959-66.

[3.] USAID Fact Sheet; 2014. Available from: http://www. factshet. [Last accessed on 2015 Dec 31].

[4.] Country Progress Report Nepal; 2015. Available from: country/documents/NPL_narrative_report_2015.pdf. [Last accessed on 2015 Dec 31].

[5.] Date HL, Fisher M. In: Walker R, Edwards C, editors. Clinical Pharmacy and Therapeutics. 3rd ed. Edinburgh: Churchill Livingstone; 2003. p. 600, 608.

[6.] Gallant JE. Initial therapy of HIV infection. J Clin Virol 2002; 25:317-33.

[7.] Mokrzycki MH, Harris C, May H, Laut J, Palmisano J. Lactic acidosis associated with stavudine administration: A report of five cases. Clin Infect Dis 2000; 30:198-200.

[8.] Bonfanti P, Ricci E, Landonio S, Valsecchi L, Timillero L, Faggion I, et al. Predictors of protease inhibitor-associated adverse events. Biomed Pharmacother 2001; 55:321-3.

[9.] Martinez E, Mocroft A, Garcia-Viejo MA, Perez-Cuevas JB, Blanco JL, Mallolas J, et al. Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: A prospective cohort study. Lancet 2001; 357:592-8.

[10.] Mocroft A, Youle M, Moore A, Sabin CA, Madge S, Lepri AC, et al. Reasons for modification and discontinuation of antiretrovirals: Results from a single treatment centre. AIDS 2001; 15:185-94.

[11.] Ammassari A, Murri R, Pezzotti P, Trotta MP, Ravasio L, De Longis P, et al. Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection. J Acquir Immune Defic Syndr 2001; 28:445-9.

[12.] d'Arminio Monforte A, Lepri AC, Rezza G, Pezzotti P, Antinori A, Phillips AN, et al. Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naive Patients. AIDS 2000; 14:499-507.

[13.] Harb GE, Alldredge BK, Coleman R, Jacobson MA. Pharmacoepidemiology of adverse drug reactions in hospitalized patients with human immunodeficiency virus disease. J Acquir Immune Defic Syndr 1993; 6:919-26.

[14.] Moore RD, Fortgang I, Keruly J, Chaisson RE. Adverse events from drug therapy for human immunodeficiency virus disease. Am J Med 1996; 101:34-40.

[15.] Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000; 356:1423-30.

[16.] Kaufmann D, Pantaleo G, Sudre P, Telenti A. CD4-cell count in HIV-1-infected individuals remaining viraemic with highly active antiretroviral therapy (HAART). Swiss HIV Cohort Study. Lancet 1998; 351:723-4.

[17.] Danner SA, Carr A, Leonard JM, Lehman LM, Gudiol F, Gonzales J, et al. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group. N Engl J Med 1995; 333:1528-33.

[18.] Fischl MA, Stanley K, Collier AC, Arduino JM, Stein DS, Feinberg JE, et al. Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group. Ann Intern Med 1995; 122:24-32.

[19.] Hammer SM, Saag MS, Schechter M, Montaner JS, Schooley RT, Jacobsen DM, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA 2006; 296:827-43.

[20.] Hennessy S, Strom BL, Berlin JA, Brennan PJ. Predicting cutaneous hypersensitivity reactions to cotrimoxazole in HIV-infected individuals receiving primary Pneumocystis carinii pneumonia prophylaxis. J Gen Intern Med 1995; 10:380-6.

[21.] Tedaldi EM, Absalon J, Thomas AJ, Shlay JC, van den Berg-Wolf M. Ethnicity, race, and gender. Differences in serious adverse events among participants in an antiretroviral initiation trial: Results of CPCRA 058 (FIRST Study). J Acquir Immune Defic Syndr 2008; 47:441-8.

[22.] Haas DW, Ribaudo HJ, Kim RB, Tierney C, Wilkinson GR, Bhandari, et a!:. Safety profile of antiretroviral therapy Gulick RM, et al. Pharmacogenetics of efavirenz and central nervous system side effects: An Adult AIDS Clinical Trials Group study. AIDS 2004; 18:2391-400.

[23.] Mensah GA, Mokdad AH, Ford ES, Greenlund KJ, CroftJB. State of disparities in cardiovascular health in the United States. Circulation 2005; 111:1233-41.

[24.] Roudiere L, Viard JP. Osteonecrosis of the hip, lipodystrophy and antiretroviral treatment. AIDS 2000; 14:2056.

[25.] Knobel H, Guelar A, Vallecillo G, Nogues X, Diez A. Osteopenia in HIV-infected patients: Is it the disease or is it the treatment? AIDS 2001; 15:807-8.

[26.] Bruno R, Sacchi P, Puoti M, Soriano V, Filice G. HCV chronic hepatitis in patients with HIV: Clinical management issues. Am J Gastroenterol 2002; 97:1598-606.

[27.] Malavaud B, Dinh B, Bonnet E, IzopetJ, Payen JL, Marchou B. Increased incidence of indinavir nephrolithiasis in patients with hepatitis B or C virus infection. Antivir Ther 2000; 5:3-5.

[28.] Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 2000; 283:74-80.

[29.] Kontorinis N, Dieterich D. Hepatotoxicity of antiretroviral therapy. AIDS Rev 2003; 5:36-43.

[30.] Lee EC, Walmsley S, Fantus IG. New-onset diabetes mellitus associated with protease inhibitor therapy in an HIV-positive patient: Case report and review. CMAJ 1999; 161:161-4.

[31.] Brown TT, Li X, Cole SR, Kingsley LA, Palella FJ, Riddler SA, et al. Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study. AIDS 2005; 19:1375-83.

[32.] Farrell GC. Drugs and steatohepatitis. Semin Liver Dis 2002; 22:185-94.

[33.] Carr A, Samaras K, Burton S, Law M, FreundJ, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12:F51-8.

[34.] Mauss S. HIV-associated lipodystrophy syndrome. AIDS 2000; 14 Suppl 3:S197-207.

[35.] Tavassoli N, Bagheri H, Sommet A, Delpierre C, Marion-Latard F, Massip P, et al. Effects of discontinuing stavudine or protease inhibitor therapy on human immunodeficiency virus-related fat redistribution evaluated by dual-energy x-ray absorptiometry. Pharmacotherapy 2006; 26:154-61.

[36.] Anonymous. The DAD Study Group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356:1723-35.

[37.] Walmsley S, Bernstein B, King M, Arribas J, Beall G, Ruane P, et al. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med 2002; 346:2039-46.

[38.] Montessori V, Press N, Harris M, Akagi L, Montaner JS. Adverse effects of antiretroviral therapy for HIV infection. CMAJ 2004; 170:229-38.

[39.] Hollmig KA, Beck SB, Doll DC. Severe bleeding complications in HIV-positive haemophiliac patients treated with protease inhibitors. Eur J Med Res 2001; 6:112-4.

[40.] Kodoth S, Bakshi S, Scimeca P, Black K, Pahwa S. Possible linkage of amprenavir with intracranial bleeding in an HIV-infected hemophiliac. AIDS Patient Care STDS 2001; 15:347-52.

[41.] Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Ann Intern Med 2002; 137 (5 Pt 2):381-433.

[42.] Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994; 331:1272-85.

[43.] D'Aquila RT, Hughes MD, Johnson VA, Fischl MA, Sommadossi JP, Liou SH, et al. Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators. Ann Intern Med 1996; 124:1019-30.

[44.] Saltel E, Angel JB, Futter NG, Walsh WG, O'Rourke K, Mahoney JE. Increased prevalence and analysis of risk factors for indinavir nephrolithiasis. J Urol 2000; 164:1895-7.

[45.] Brau N, Leaf HL, Wieczorek RL, Margolis DM. Severe hepatitis in three AIDS patients treated with indinavir. Lancet 1997; 349:924-5.

[46.] Picard O, Rosmorduc O, Cabane J. Hepatotoxicity associated with ritonavir. Ann Intern Med 1998; 129:670-1.

[47.] Piroth L, Grappin M, Sgro C, Buisson M, Duong M, Chavanet P. Recurrent NNRTI-induced hepatotoxicity in an HIV-HCV-coinfected patient. Ann Pharmacother 2000; 34:534-5.

[48.] Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: Contribution to protease inhibitor-related lipodystrophy syndrome. AIDS 2000; 14:F25-32.

[49.] Bonnet F, Balestre E, Bernardin E, Pellegrin JL, Neau D, Dabis F; Groupe d'Epidemiologie Clinique du SIDA en Aquitaine. Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999-2003. Antivir Chem Chemother 2005; 16:63-7.

[50.] John M, Moore CB, James IR, Nolan D, Upton RP, Bhandari, et a!:. Safety profile of antiretroviral therapy McKinnon EJ, et al. Chronic hyperlactatemia in HIV-infected patients taking antiretroviral therapy. AIDS 2001; 15:717-23.

[51.] Chattha G, Arieff AI, Cummings C, Tierney LM Jr. Lactic acidosis complicating the acquired immunodeficiency syndrome. Ann Intern Med 1993; 118:37-9.

[52.] Watts DH. Teratogenicity risk of antiretroviral therapy in pregnancy. Curr HIV/AIDS Rep 2007; 4:135-40.

[53.] Wulff EA, Wang AK, Simpson DM. HIV-associated peripheral neuropathy: Epidemiology, pathophysiology and treatment. Drugs 2000; 59:1251-60.

[54.] Adkins JC, Noble S. Efavirenz. Drugs 1998; 56:1055-64.

[55.] Clifford DB, Evans S, Yang Y, Acosta EP, Goodkin K, Tashima K, et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med 2005; 143:714-21.

[56.] Dalakas MC. Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst 2001; 6:14-20.

[57.] Simpson DM, Tagliati M. Nucleoside analogue-associated peripheral neuropathy in human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 9:153-61.

[58.] Blum AS, Dal Pan GJ, Feinberg J, Raines C, Mayjo K, Cornblath DR, et al. Low-dose zalcitabine-related toxic neuropathy: Frequency, natural history, and risk factors. Neurology 1996; 46:999-1003.

[59.] Dolin R, Amato DA, Fischl MA, Pettinelli C, Beltangady M, Liou SH, et al. Zidovudine compared with didanosine in patients with advanced HIV type 1 infection and little or no previous experience with zidovudine. AIDS Clinical Trials Group. Arch Intern Med 1995; 155:961-74.

[60.] Shelburne SA 3rd, Hamill RJ. The immune reconstitution inflammatory syndrome. AIDS Rev 2003; 5:67-79.

[61.] French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS 2004; 18:1615-27.

[62.] Mehta N, Reilly M. Atherosclerotic cardiovascular disease risk in the HAART-treated HIV-1 population. HIV Clin Trials 2005; 6:5-24.

[63.] Hester EK, Chandler HV, Sims KM. Fosamprenavir: Drug development for adherence. Ann Pharmacother 2006; 40:1301-10.

[64.] Karras A, Lafaurie M, Furco A, Bourgarit A, Droz D, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus infected patients: Three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis 2003; 36:1070-3.

[65.] Wislez M, Bergot E, Antoine M, Parrot A, Carette MF, Mayaud C, et al. Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 2001; 164:847-51.

[66.] Fellay J, Boubaker K, Ledergerber B, Bernasconi E, Furrer H, Battegay M, et al. Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study. Lancet 2001; 358:1322-7.

[67.] Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: A cohort study. Lancet 1999; 353:2093-9.

[68.] Fortgang IS, Belitsos PC, Chaisson RE, Moore RD. Hepatomegaly and steatosis in HIV-infected patients receiving nucleoside analog antiretroviral therapy. Am J Gastroenterol 1995; 90:1433-6.

[69.] den Brinker M, Wit FW, Wertheim-van Dillen PM, Jurriaans S, Weel J, van Leeuwen R, et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS 2000; 14:2895-902.

[70.] Scribner AN, Troia-Cancio PV, Cox BA, Marcantonio D, Hamid F, et al. Osteonecrosis in HIV: A case-control study. J Acquir Immune Defic Syndr 2000; 25:19-25.

[71.] Clay PG. The abacavir hypersensitivity reaction: A review. Clin Ther 2002; 24:1502-14.

[72.] Hewitt RG. Abacavir hypersensitivity reaction. Clin Infect Dis 2002; 34:1137-42.

[73.] Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet 2006; 367:1747-57.

[74.] Henry K. The case for more cautious, patient-focused antiretroviral therapy. Ann Intern Med 2000; 132:306-11.

[75.] Shigdel R, Klouman E, Bhandari A, Ahmed LA. Factors associated with adherence to antiretroviral therapy in HIV-infected patients in Kathmandu District, Nepal. HIV AIDS (Auckl) 2014; 6:109-16.

[76.] Bam K, Rajbhandari RM, Karmacharya DB, Dixit SM. Strengthening adherence to antiretroviral therapy (ART) monitoring and support: Operation research to identify barriers and facilitators in Nepal. BMC Health Serv Res 2015; 15:188.

[77.] Programmatic Update on Antiretrovirals Maximizing the Treatment and Prevention Potential of Antiretroviral Drugs: Early Country Experiences towards Implementing a Treat-all Policy; 2015. Available from: http://www.apps.who. int/iris/bitstream/10665/183599/1/WHO_HIV_2015.35_ eng.pdf?ua=1. [Last accessed on 2016 Apr 01].

[78.] Gunthard HF, Aberg JA, Eron JJ, Hoy JF, Telenti A, Benson CA, et al. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA 2014; 312:410-25.

[79.] Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Department of Health and Human Services. Available from: http://www. pdf. [Last accessed on 2016 Apr 01].

Dhaka Ram Bhandari, Subish Palaian (1), Arjun Poudel (2), Mohamed Izham B. Mohamed Ibrahim (3), Hisham Aljadhey (4)

Institute of Inorganic and Analytical Chemistry, Giessen, Germany, (1) Gulf Medical University, Ajman, United Arab Emirates, (2) School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia, (3) College of Pharmacy, Qatar University, Doha, Qatar, (4) College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia

Address for correspondence:

Dr. Dhaka Ram Bhandari, Institute of Inorganic and Analytical Chemistry, Giessen, Germany. E-mail:
COPYRIGHT 2016 Archives of Pharmacy Practice
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2016 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Short Communication
Author:Bhandari, Dhaka Ram; Palaian, Subish; Poudel, Arjun; Ibrahim, Mohamed Izham B. Mohamed; Aljadhey, Hi
Publication:Archives of Pharmacy Practice
Article Type:Report
Date:Apr 1, 2016
Previous Article:Promoting rational self-medication of nonsteroidal anti-inflammatory drugs in Nepal.
Next Article:Use of herbal products in Southeast Asian countries.

Terms of use | Privacy policy | Copyright © 2022 Farlex, Inc. | Feedback | For webmasters |