Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults

Aim: To estimate the effectiveness of triple combination therapy in antiret roviral-naive adults. Methods: A systematic overview of results from clinical trials involving tr iple combination therapy with dual nucleoside reverse transcriptase inhibit ors (NRTI) and: a protease inhibitor (PI triple); a non-nucleoside reverse transcriptase inhibitor (NNRTI triple); or a third NRTI (triple NUC). Data from 23 clinical trials involving 31 independent treatment groups, 19 uniqu e antiretroviral regimens, and 3257 enrolled patients were included in this study. Results: Median log(10) baseline plasma HIV RNA and CD4 cell count over all trials averaged 4.69 (49 329 copies/ml) and 375 x 10(6) cells/l, respectiv ely. The overall estimated percentage of patients with plasma HIV RNA less than or equal to 400 copies/ml at 24 weeks was 64% [95% confidence interval (CI), 60 to 67%]. The percentages of patients with plasma HIV RNA less tha n or equal to 50 copies/ml at 48 weeks by drug class were: PI triple, 46% ( 95% CI, 41 to 52%); NNRTI triple, 51% (95% CI, 43 to 59%); triple NUC, 45% (95% CI, 36 to 54%). The CD4 cell count increase over all trials at 24 and 48 weeks averaged +123 x 10(6) cells/l (95% CI, 111 x 10(6) to 135 x 10(6) cells/l) and +160 x 10(6) cells/l (95% CI, 146 x 10(6) to 175 x 10(6) cells /l), respectively and did not differ between drug classes, in multivariable regression analysis, neither baseline plasma HIV RNA level and CD4 cell co unt nor treatment regimen predicted plasma HIV RNA less than or equal to 50 copies/ml at week 48. However, pill count was significantly negatively ass ociated with plasma HIV RNA less than or equal to 50 copies/ml at week 48 ( P = 0.0085). Conclusions: The results suggest that three drug regimens containing two NR TI with a PI, a NNRTI, or a third NRTI may provide comparable activity, and practical issues such as daily pill burden should be considered when choos ing a treatment regimen. (C) 2001 Lippincott Williams & Wilkins