Comparison of initial combination antiretroviral therapy with a single protease inhibitor, ritonavir and saquinavir, or efavirenz

Objective: To compare the effectiveness of initial highly active antiretroviral therapy with either: a single protease inhibitor (PI); ritonavir (RTV)/saquinavir (SQV); or efavirenz (EFV) plus nucleoside reverse transcriptase inhibitors. Design: Cohort study. Setting: Urban HIV clinic. Patients: Five-hundred and forty-five HIV-1-infected individuals with minimal antiretroviral exposure who started combination therapy with ≥ 3 antiretroviral drugs and ≥ 1 NRTI to which they had not previously been exposed (single PI, 416; RTV/SQV, 68; EFV, 61). Main outcome measures: HIV-1 RNA < 400 copies/mi within 8 months of starting therapy; time to HIV-1 RNA rebound to > 1000 copies/ml in the subset of patients achieving initial viral suppression; change in CD4 cell count from baseline within 12 months of starting therapy. Results: By intent-to-treat analysis, initial viral suppression was achieved by 72% of patients in the EFV group, compared to 49% in the single PI group (P= 0.001) and 51% in the RTV/SQV group (P = 0.019). Among patients who achieved initial viral suppression, time to viral rebound was similar in the three groups. Durable viral suppression (≥ 3 consecutive HIV-1 RNA levels < 400 copies/mi for > 6 months) was achieved by 53% of patients in the EFV group, 26% in the single PI group, and 29% in the RTV/SQV group (P< 0.05 for both comparisons with EFV). The median CD4 cell count increase was 139 × 10⁶ cells/l, and was similar in the three groups. Conclusions: In agreement with a recent clinical trial, use of initial EFV-based combination antiretroviral therapy was associated with higher rates of viral suppression than PI-based therapy in a clinical cohort.