An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults

Objective: To compare the effectiveness of three drug combination antiretroviral therapy (ART) in treatment-naive HIV-infected persons, and identify the predictors of responses. Design and methods: Overview of trials identified by searching public domain publications and conference presentations. The three-drug combination therapy was defined as two nucleoside reverse transcriptase inhibitors (NRTI) or nucleoticle and NRTI, and either: (1) a protease inhibitor (PI); (2) a non-nucleoside RTI (NNRTI); (3) a third NRTI; or(4) a ritonavir-boosted PI (BPI). Week24and48 results for the proportions of patients with plasma HIV RNA levels < 400 and < 50copies/ml, and change in CD4+ cell counts were recorded. Results: Fifty-three trials met the entry criteria, and enrolled 14264 patients into 90 treatment arms. Overall 55% of patients had plasma HIV RNA levels < 50 copies/ml at week 48 and this percentage increased with later publication dates. In unadjusted pairwise comparisons at week 48, significantly greater percentages of patients receiving NNRTI (64%) and BPI (64%) had RNA < 50 copies/ml than NRTI (54%) or PI (43%), and CD4+ cell count increases were significantly greater in the BPI group (+200cells/mu l) than the PI (+179), NNRTI (+173), or NRTI (+161) groups. Pill count and percentage of patients with week 48 plasma HIV RNA levels < 50 copies/ml were correlated in the univariate analysis (P=0.0053; r=-0.323), but pill count was not a significant predictor in the multivariate analyses. Drug class and baseline CD4+ cell counts were significant predictors, but explained only a modest amount of the treatment effect, (R-2 = 0.355). Conclusions: NNRTI and BPI-containing regimens offer superior virologic suppression over 48 weeks, supporting existing guidelines for the choice of initial ART. Pill count was not a consistent predictor of virologic suppression. (c) 2006 Lippincott Williams & Wilkins.