|
|
Meta-Analysis of Efficacy of Triple Combination Therapy in Antiretroviral-Naive HIV-1-Infected Adults J. BARTLETT*1, R. DEMASI2, J. QUINN2, C. MOXHAM2, and F. ROUSSEAU2. 1Duke Univ., Durham, NC; and 2Triangle Pharmaceuticals, Durham, NC Although numerous clinical trials comparing the efficacy of triple combination therapy have been conducted, to date there has been no synthesis of the results across similarly designed clinical trials. To estimate antiviral efficacy and assess its variability across different drug classes, we performed a systematic overview of results from published trials in antiretroviral (ART)-naïve HIV-1 infected adults involving triple combination therapy with dual nucleoside reverse transcriptase inhibitors and: 1) a protease inhibitor (PI triple); 2) a nonnucleoside reverse transcriptase inhibitor (NNRTI triple); or 3) a third NRTI (triple NUC). All studies were of at least 24 weeks in duration and plasma HIV1 RNA was assessed by the Roche Amplicor Monitors® assay. Estimates of the percentage of patients with undetectable plasma HIV-1 RNA were calculated using intent-to-treat analyses, thereby allowing meaningful comparison of standardized results across different clinical trials. 18 clinical trials involving 24 different triple therapy treatment regimens studied in 2,271 subjects published/presented by October 1, 1999 were included in this study. Median baseline plasma HIV-1 RNA and CD4+ cell count were 46,773 copies/mL and 377 cells/mm3, respectively. The estimated percentage of patients (95% C.I.) with plasma HIV-1 RNA <400 copies/mL at 24 weeks by drug class were: PI triple, 63% (57%, 68%); NNRTI triple, 65% (57%, 74%); and triple nuc, 67% (58%, 76%). The overall estimate of the percentage of patients with <50 copies/mL was comparable across drug classes (PI triple, 49% [42%, 55%]; NNRT triple, 51% [41%, 61%]; triple nuc, 49% [34%, 64%] and was correlated with baseline plasma HIV-1 RNA (r=–0.49, p=0.01 5). CD4+ cell count increase at 24 weeks averaged +114 cells/mm3 across trials. In conclusion, the 24 week efficacy results of triple combination therapy in ART-naïve patients are similar across triple drug classes. Key Words: CD4 cell count, clinical trial, plasma HIV-1 RNA |
|
© 7th
Conference on Retroviruses and Opportunistic Infections, |