In a widely-cited study published in 2001, John Bartlett from Duke University conducted an exhaustive overview of 23 triple-therapy studies of HIV infection.¹ This meta-analysis came to several important conclusions, most notably that pill burden was strongly negatively associated with therapy success -- in other words, treatments with a greater number of daily pills/day were less likely to lead to virologic suppression. In this study, Bartlett updates his review by including studies that were published or presented through February 2004.

For inclusion in this study, trials needed to be 24 weeks or longer in duration, and have at least 30 subjects per treatment arm; excluded were studies of acute HIV infection. Only trials of antiretroviral-naive or minimally treated patients were reviewed. The primary endpoints of interest were the proportion of subjects with an undetectable viral load at week 48 by intention-to-treat analysis, as well as the CD4+ cell response.

Forty-nine clinical trials met the inclusion criteria, representing a more than doubling of studies over the prior report, with data on over 13,000 patients. Overall, 57% of the patients achieved a viral load of less than 50 copies at week 48, with a corresponding CD4+ cell response of 177 cells -- both improvements over the prior report, and strongly supporting the notion that treatment has improved over time.

In a multivariate analysis to evaluate predictors of virologic suppression, boosted protease inhibitor (PI)- and non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens were associated with a greater likelihood of virologic suppression than nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-only or non-boosted PI regimens, but lower pill burden no longer predicted a higher rate of response. Interestingly, boosted PI-containing regimens demonstrated a greater increase in CD4+ cell response than the others did.

This comprehensive analysis provides support for the treatment guidelines from the Department of Health and Human Services and the International AIDS Society, which recommend efavirenz (EFV, Sustiva, Stocrin) or a boosted PI as initial therapy.

The finding that treatment has improved over time is particularly encouraging, especially in light of another finding of this review. The other finding was that the CD4+ cell counts of participants entering treatment-naive studies have declined compared with those of the early combination antiretroviral therapy era -- and hence, such study participants today should be, if anything, harder to treat. The observation that lower pill burden no longer correlates with treatment response likely represents an overall move since 2001 towards more "compact" regimens, which have now become the standard of HIV care.

Footnote

1. Bartlett JA, DeMasi R, Quinn J, Moxham C, Rousseau F. Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS. July 27, 2001;15(11):1369-1377.