Zidovudine, tenofovir or abacavir? Different adverse effect profiles

Current guidelines on first-line treatment of HIV infection recommend a combination of at least three antiretroviral drugs from two different pharmacological classes: at least two nucleoside or nucleotide reverse transcriptase inhibitors plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. Among the available nucleoside or nucleotide inhibitors, some guidelines recommend the tenofovir + emtricitabine combination for adults. The abacavir + lamivudine and zidovudine + lamivudine combinations have similar efficacy but are only considered alternative options. What is known of the differences in adverse effects between zidovudine, tenofovir and abacavir? How should their respective adverse effect profiles influence the choice between available combinations? We sought answers to these questions by reviewing the literature using the standard Prescrire methodology. Treatment withdrawals for adverse effects or fear of lipoatrophy are less frequent with tenofovir than with zidovudine. Similarly, treatment withdrawals because of adverse effects are less frequent with abacavir+ lamivudine than with tenofovir + emtricitabine. Zidovudine mainly has haematological adverse effects (anaemia, leukopenia) and also causes lipoatrophy. Tenofovir mainly causes renal disorders (tubulopathy, Fanconi syn- drome), bone disorders (osteoporosis, fractures, osteomalacia) and gastrointestinal disorders. Abacavircan cause life-threatening hypersensitivity reactions, even (al- beit less frequently) in patients who do not carry the HLA-B*5701 allele. It probably also has cardiovascular adverse effects, including myocardial infarction. In practice, the choice between the tenofovir + emtricitabine, abacavir + lamivudine or zidovudine + lamivudine combinations should be made on a case-by-case basis, taking into account the patient's renal function, hepatitis B virus serostatus, and other ongoing treatments, as well as poten- tial adverse effects, treatment moni- toring, and convenience.