Elsevier

The Lancet

Volume 356, Issue 9239, 21 October 2000, Pages 1423-1430
The Lancet

Adverse Drug Reactions
Adverse effects of antiretroviral therapy

https://doi.org/10.1016/S0140-6736(00)02854-3Get rights and content

Summary

Antiretroviral toxicity is an increasingly important issue in the management of HIV-infected patients. With the sustained major declines in opportunistic complications, HIV infection is a more chronic disease, and so more drugs are being used in more patients for longer periods. This review focuses on the pathogenesis, clinical features, and management of the principal toxicities of the 15 licensed antiretroviral drugs, including mitochondrial toxicity, hypersensitivity, and lipodystrophy, as well as more drug-specific adverse effects and special clinical settings.

Section snippets

Mitochondrial toxicity

Nucleoside and monophosphorylated nucleotide-analogue reverse-transcriptase inhibitors (NRTIs and NtRTIs, respectively) are both phosphorylated intracellularly to active triphosphate forms, and are then incorporated into new DNA strands synthesised by HIV reverse transcriptase.3, 4 The lack of a 3′ hydroxyl in NRTIs and NtRTIs results in HIV DNA chain termination.

The major toxicities of NRTI and NtRTI therapy, particularly over the medium-term to long-term, are thought to be secondary to

Hypersensitivity

Drug hypersensitivity typically manifests as an erythematous, maculopapular, pruritic, and confluent rash with or without fever (figure 1, panel 1).15 The rash is most prominent on the body and arms and usually begins after 1–3 weeks' therapy. Constitutional features (fever, rigors, myalgias, and arthralgias) are often prominent, and can precede the rash (particularly with abacavir) or occur without rash. Stevens-Johnson syndrome or toxic epidermal necrolysis develops in less than 0·5% of

Clinical and metabolic features

A syndrome (or syndromes) of lipodystrophy affecting HIV-1-infected patients was first described only 2 years ago. The main clinical features are peripheral fat loss (presumed lipoatrophy in the face, limbs, and buttocks) and central fat accumulation (within the abdomen, breasts, and over the dorsocervical spine [so-called “buffalo hump”], as well as other lipomata; figure 2, panel 2).21, 22 These changes have been objectively confirmed by dual-energy X-ray absorptiometry (DEXA) and abdominal

Other adverse events and special circumstances

Numerous antiretrovirals have specific adverse effects, many of uncertain pathogenesis (table 3), and others cause problems in particular circumstances. General principles of management are given in panel 3, and some common adverse effects are discussed below.

Future directions

The type and timing of antiretroviral therapy will be increasingly influenced by their potential toxicities as well as by more traditional biological criteria. Toxicities will also have an impact on patients' tolerability and adherence to often complex antiretroviral regimens, particularly for patients receiving so-called salvage or intensification regimens, which can comprise up to seven antiretroviral drugs. Therefore, assays that predict or more readily diagnose drug-induced toxicity are

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