Institutional members access full text with Ovid®

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

Bartlett, John Aa; Fath, Michael Jb; DeMasi, Ralphc; Hermes, Ashwaqb; Quinn, Josephd; Mondou, Elsad; Rousseau, Franckd

doi: 10.1097/01.aids.0000247578.08449.ff
Clinical Science

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 nucleotide 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). Week 24 and 48 results for the proportions of patients with plasma HIV RNA levels < 400 and < 50 copies/ml, and change in CD4+ cell counts were recorded.

Results: Fifty-three trials met the entry criteria, and enrolled 14 264 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 (+200 cells/μl) 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, (R2 = 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.

From the aDuke University Medical Center, Durham, North Carolina, USA

bAbbott Laboratories, Abbott Park, Illinois, USA

cTrimeris Inc, Morrisville, North Carolina, USA

dGilead Sciences, Durham, North Carolina, USA.

Received 3 March, 2006

Accepted 26 June, 2006

Correspondence to John A. Bartlett, Box 3152, Durham, North Carolina, 27710, USA. E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.