Adverse effects of antiretroviral therapy for HIV infection

Abstract

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

Fig. 1: Adverse effects of antiretroviral therapy. In some cases, only a certain drug causes the effect (drug name in parentheses). Photo: Chesley Sheppard

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Fig. 2: Postulated mechanism by which nucleoside reverse transcriptase inhibitor (NRTI) therapy interferes with glycolysis, leading to lactic acidosis. Dashed lines indicate steps occurring within the mitochondria, for which normal mitochondrial function is required. These steps are subject to impairment by NRTI therapy. If such impairment occurs, pyruvate and NADH accumulate, enhancing the conversion of pyruvate into lactate, which ultimately leads to lactic acidosis. AcetylCoA = acetylcoenzyme A, ATP = adenosine triphosphate, LDH = lactate dehydrogenase, NAD = nicotinamide adenine dinucleotide, NADH = reduced form of NAD.

Fig. 3: Clinical features of lipodystrophy. Top: Dorsocervical fat pad. Bottom: Central fat accumulation with abdominal skin striae and thinning of the extremities. Reproduced, with permission, from the Canadian Respiratory Journal.