Long-term safety and tolerability of the lamivudine/abacavir combination as components of highly active antiretroviral therapy.

Background: Numerous large, long-term clinical trials have assessed the safety and efficacy of the two antiretroviral nucleoside analogs lamivudine and abacavir as components of highly active antiretroviral therapy for the treatment of patients with HIV-1 infection. This analysis pools the safety data on multi-drug regimens containing lamivudine/abacavir in combination with a protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or nucleoside reverse transcriptase inhibitor.

Methods: Data are presented from 2279 treatment-naive HIV-1-infected patients who were enrolled in one of five clinical trials that assessed the safety and tolerability of lamivudine/abacavir in combination with a third antiretroviral agent. The well characterised combination of lamivudine/zidovudine plus efavirenz was used as the comparator arm. All available safety data (including data beyond 48 weeks) were used in all analyses, which included calculation of treatment emergent laboratory values, adverse events (AEs), serious AEs, fatalities, drug discontinuations and any summaries by study week of safety data.

Results: In the total lamivudine/abacavir group, 1585 of 2229 (71%) patients experienced at least one drug-related AE during the study compared with 247 of 325 (76%) patients in the lamivudine/zidovudine/efavirenz treatment group. The most common drug-related AEs reported during the study were diarrhoea (19%), nausea (18%) and dizziness (12%) in patients treated with lamivudine/abacavir plus a third agent, and nausea (31%), dizziness (27%) and headache (16%) in the comparator group. Overall, in the total lamivudine/abacavir group there were only three severe (Division of AIDS 1992 toxicity table grade 3 or 4) AEs that were reported in >1% of subjects: drug hypersensitivity, elevated ALT levels and elevated AST levels. In the lamivudine/zidovudine/efavirenz group, six severe AEs that occurred in >1% of the safety population were reported. The abacavir hypersensitivity reaction rate reported in these five studies was comparable with the previously reported rate. In addition, there were no patient fatalities attributed by investigators to the study drugs.

Conclusion: This analysis indicates that the combination of lamivudine/abacavir is generally safe for the majority of patients when used as part of combination therapy.