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.


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/microl) 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.
Bartlett
John A
JA
Duke University Medical Center, Durham, North Carolina 27710, USA. jab5@duke.edu
Fath
Michael J
MJ
Demasi
Ralph
R
Hermes
Ashwaq
A
Quinn
Joseph
J
Mondou
Elsa
E
Rousseau
Franck
F
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors