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Two large observational studies — ART-CC and NA-ACCORD (JW AIDS Clin Care Apr 17 2009) — demonstrated the merits of starting antiretroviral therapy (ART) in patients with CD4 counts between 350 and 500 cells/mm3. Now, a third such study (from the HIV-CAUSAL Collaboration) further informs the debate about when to start ART.
A total of 8392 treatment-naive, HIV-infected patients were followed for a median of 12 months from the time their CD4 counts dropped below 500 cells/mm3. Outcomes of interest were mortality and new AIDS-related events, relative to when combination ART was started.
Delaying ART until CD4 counts dropped to 350 cells/mm3, rather than initiating treatment at 500 cells/mm3, was associated with a nearly 40% increase in the combined endpoint of AIDS-defining illness or death. Such a delay, however, did not increase all-cause mortality alone. The authors estimated that 48 patients would need to be treated at CD4 counts of 500 versus 350 cells/mm3 to prevent one case of AIDS-related illness or death.
The H. IV-CAUSAL Collaboration. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: An observational study. Ann Intern Med 2011 Apr 19; 154:509.
Baker JV and Henry K. If we can't get what we want, can we get what we need? Optimizing use of antiretroviral therapy in the current era. Ann Intern Med 2011 Apr 19; 154:563.
Comment
Although not the blockbuster results of the NA-ACCORD study — whose nearly 50% reduction in mortality for starting at CD4 counts >500 cells/mm3 remains both unreproduced and unexplained — these results still point to a substantial clinical benefit from starting ART before CD4-cell counts fall too low. In addition, none of these large observational studies even hints that starting early could have a negative effect on clinical outcomes, and none addresses the potential population-based benefits of treating HIV infection (reduced risk of HIV transmission, reduced long-term incidence of non-AIDS events). As nicely summarized in the accompanying editorial, the relative clinical benefits of starting ART in someone with high CD4-cell counts are nowhere near as great as treating someone with advanced AIDS, but such a strategy might be worthwhile nonetheless. It's up to us — physicians, patients, society — to decide whether early ART is worthwhile.