Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 infection: the OzCombo 2 study

Purpose: To assess and compare the efficacy and safety of three triple combination antiretroviral therapies in HIV-1-infected treatment-naive patients. Method: Seventy treatment-naive HIV-infected adults with CD4+ T-cell counts >50/μL were randomized to receive either zidovudine + lamivudine + nevirapine (AZT+3TC+NVP), stavudine + didanosine + nevirapine (d4T+ddl+NVP), or stavudine + lamivudine + nevirapine (d4T+3TC+NVP) for 52 weeks. Patient assessments were conducted monthly and included measurement of plasma HIV RNA levels and CD4+ T-cell counts and evaluations for drug toxicity. Results: The mean time-weighted reductions in plasma HIV RNA in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddl+NVP groups were 1.29, 2.13, and 1.78 log₁₀ copies/mL, respectively (p = .389). The proportions of patients with HIV RNA <50 copies/mL in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddl+NVP groups were 73%, 68%, and 80%, respectively (p = .71). The mean time-weighted increases in CD4+ T-cell counts in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddl+NVP groups were 139, 113, and 174 cells/μL, respectively (p = .30). Three patients ceased assigned treatment due to rash (one from each treatment arm), and 5 of the 45 patients on d4T (3 from the d4T+3TC+NVP arm and 2 from the d4T+ddl+NVP arm) ceased assigned treatment due to neuropathy. Conclusion: All three-drug combinations were equally effective at suppressing viral load and increasing CD4+ T-cell counts. No significant differences were detected between the treatment groups in virological or immunological response or cessation of study drugs due to adverse events, although it is possible that the study was underpowered to detect differences. NVP was safe and efficacious in this setting, and efficacy was not influenced by nucleoside reverse transcriptase inhibitor backbone.