A. When you are forced to end it early.
That is exactly what happened with the CIPRA HT 001 clinical trial on ART initiation conducted by NIAID supported researchers in Haiti. About 800 patients presenting with clinical HIV disease and CD4 counts ranging between 200 and 350 were randomized to receive ART treatment nearly immediately, or once they reached a CD4 cell count below 200 (current standard practice in developing countries). After approximately 3 years, there was a nearly 4 fold difference in mortality rates among the groups (23 vs. 6 deaths) and also significantly lower rates of TB incidence. When differences this striking emerge from clinical trials, it is generally considered unethical to continue them and thus they are stopped and everyone is given the superior treatment.
Evidence has been accumulating for years about the benefits of early treatment in terms of decreased mortality, but because none of the previous studies were randomized trials, some skepticism remained. Unobserved severity of patients by themselves and their providers always weakened the findings of such studies, despite the fact that the differences between the groups were relatively large.
I’ve blogged about the implications of early treatment before (here and here). Current treatment guidelines are based on a belief that drugs should be rationed to the sickest patients first, but this evidence suggests that treating patients earlier may do more to save lives. It means is that for the same resource envelope fewer people will receive treatment if earlier treatment protocols are adopted (since they live longer) or that more resources will be needed to treat the same number of people (note this is not saying that one approach is more cost-effective than another, this is a different argument). What I find most remarkable about this study is that they were comparing relatively sick patients to slightly sicker patients (earlier studies looked at even higher CD4 cut offs than here) and still finding these differences. What if they had started with CD4 initiation levels that are sometimes used in developed countries?
It seems some serious debating, and potentially revising, of treatment guidelines is on its way.Share on Facebook