There has been a long standing debate in the clinical literature about the optimal time to commence ARV therapy. I have blogged about this debate before. It is something I know a little about since it was related to my hono(u)rs thesis in undergrad (what we Canadians call “college” because we go to University not college) back in the late 1990s.
In the absence of a randomized trial, this debate has raged on for over a decade. Although guidelines have generally supported the view that earlier is better, concerns over resistance and side-effects led to treatment being initiated on average much later in many cases. In resource poor areas, guidelines have generally adopted the view that ARVs should be prioritized to those who are the sickest – a reasonable value judgement in the context of more limited financial resources. But how likely is it that these treatment guidelines do the most to save lives?
But say it was survival that we really cared about than what should we do? A recent large prospective cohort study conducted since the mid-1990s in the US and Canada and recently published in the New England Journal of Medicine finds that earlier the better when it comes to survival – much better in fact. Comparing patients that initiate treatment at higher CD4 blood cell counts to those with lower levels the study found very large differences in survival probabilities. Initiating at CD4 counts above 500 was associated with nearly a doubling of the survival probability to those that deferred treatment. Initiating above 350 vs. lower also had significantly higher survival probabilities. Given the large sample size of this study, they were able to control for factors that are believe to be predictors for mortality. This is certainly no substitute for conducting a randomized trial, but it does improve the generalizability of these findings.
While it goes without saying that because these findings are based on observational data, they should be interpreted cautiously. In terms of the biases, it seems reasonable to think that the healthiest patients may be those who would be likely to defer treatment at any given CD4 count level, which would only strengthen these findings. Regardless, these findings do seriously question current ARV treatment guidelines, in particular in resource poor settings.
Would ARV resources most appropriately allocated to patients with higher CD4 counts not the reverse? Should we care about cost-effetiveness or just survival?
By the way, Kudos to the New England Journal for making some of their top articles free to readers.Share on Facebook