An ongoing dialogue on HIV/AIDS, infectious diseases,
April 18th, 2011
When to Start Antiretroviral Therapy, Take 3
A third observational study on “When to Start ART” has just appeared in the Annals of Internal Medicine, “The HIV-CAUSAL Collaboration.”
As with ART-CC and NA-ACCORD, it’s a large study, starting with over 20,000 people with HIV with baseline CD4s >500 receiving care in Europe and the United States. Out of this group, 8392 experienced CD4 declines into the 200-500 range and are included in this analysis. Outcomes of interest are mortality and new AIDS-related events, depending on when combination ART (“cART”) was started.
Initiation of cART at a threshold CD4 count of 500 increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 300 and 500.
The authors also cite a “number needed to treat” of 48 for starting at 500 rather than 350 for prevention of AIDS or death, a fairly low number when compared to some interventions widely adopted in cardiovascular disease.
While not the blockbuster results of the NA-ACCORD study — whose nearly two-fold reduction in mortality for starting at >500 remains both unreproduced and, let’s face it, unexplained — these results still point to a substantial clinical benefit of starting ART before CD4s fall too low.
In addition, none of these large observational studies even hints at a negative effect of starting early on clinical outcomes, and other potential benefits of treating HIV (reduced risk of HIV transmission, reduced long-term incidence of non-AIDS events) can’t be included.
As nicely summarized in the accompanying editorial, the quantitative benefits of early ART can’t come close to the benefits of late ART, which are nothing short of miraculous.
It’s up to us — patients, providers, society — to determine whether early ART is worth it.