A randomised, open-label comparison of three highly active antiretroviral therapy regimens including two nucleoside analogues and indinavir for previously untreated HIV-1 infection: the OzCombo1 study

Background: Highly active antiretroviral therapy (HAART) including two nucl eoside analogues and a potent protease inhibitor is standard of care initia l therapy for HIV-infected adults. The best-tolerated and most potent initi al HAART regimen is unknown and was investigated in this study. Methods: One hundred and nine HIV-infected adults with no prior antiretrovi ral therapy, and CD4 lymphocyte counts <500 x 10(6) cells/l or plasma HIV R NA > 30 000 copies/ml were randomized to zidovudine-lamivudine-indinavir (Z DV-3TC-IDV), stavudine-lamivudine-indinavir (d4T-3TC-IDV) or stavudine-dida nosine-indinavir (d4T-ddI-IDV) for 52 weeks. The primary endpoints were pla sma HIV RNA and drug-related adverse events. Other assessments were overall safety, adherence and adverse events, CD4 lymphocyte counts, cutaneous del ayed type hypersensitivity (DTH) responses and quality of life (Euroqol). Results: Only 58% patients had HIV RNA < 50 copies/ml plasma at 12 months, with no significant difference between the three regimes (P = 0.34). Drug-r elated adverse events sufficiently severe to warrant drug discontinuation w ere less common (P = 0.06) in patients receiving d4T-3TC-IDV (18%) than in those receiving ZDV-3TC-IDV (34%) or d4T-ddI-IDV (41%). The percentages of patients who remained on their assigned therapy with plasma HIV RNA < 50 co pies/ml at 52 weeks were 60% with d4T-3TC-IDV, 53% with ZDV-3TC-IDV and 35% with d4T-ddI-IDV. Virological failure at 52 weeks was more likely in those whose adherence was estimated to be < 100% in the first 4 weeks of therapy (P = 0.02), but not in those who developed grade 3 or 4 drug-related adver se events. At 52 weeks, the mean CD4 lymphocyte count increase was 200 x 10 (6) cells/l with only 7% of patients having counts lower than at baseline; DTH responses improved but remained clinically impaired in most patients. Q uality of life improved significantly in all groups. Conclusions: Initial HAART regimens including IDV failed to suppress plasma HIV RNA to < 50 copies/ml in > 40% patients after only 12 months of therap y although there was significant overall improvement immunologically and in quality of life. The type of dual nucleoside combination used was less imp ortant in predicting virological Failure than was imperfect adherence early in therapy. Consideration should be given to modifying a HAART regimen rel atively early in non-adherent patients. (C) 2000 Lippincott Williams & Wilk ins.