A second large cohort study has confirmed that starting antiretroviral (ARV) therapy before CD4 counts fall to 350 or below—which is the current guidelines cutoff—protects against developing an AIDS diagnosis and death, according to the authors of a study published online April 9 in The Lancet and reported by aidsmap.

The scientific argument about the ideal time to start ARV therapy is a hot one right now. A recent study published in The New England Journal of Medicine found that the earlier a person started treatment, even before CD4 counts fell to 350 or below, the more likely he or she was to be free of AIDS- and non-AIDS-defining illnesses and death.

Other researchers have cautioned, however, that these large cohort studies are not designed to prove whether starting or delaying therapy is superior, neither in terms of survival, nor in terms of safety. Nevertheless, the When to Start Consortium, a collective of researchers from 18 HIV cohort studies, has published in The Lancet a report whose analysis is more like a traditional controlled clinical trial, which is the gold standard for biomedical research.

The consortium evaluated the medical records of 24,444 people who had CD4 counts less than 550 but had neither taken ARV treatment nor had an AIDS-defining illness. Of those patients, 21,247 were followed since the mid- or late 1990s, when combination therapy was introduced.

The researchers found that waiting to start treatment was harmful. People who deferred treatment until CD4 counts fell into a range of 251 to 350 cells had higher rates of AIDS-defining illnesses and AIDS-related deaths than people who started treatment with CD4 counts between 351 and 450. Non-AIDS-related deaths were also higher in people who waited to start treatment than in people who started treatment early, though the difference was not as great as that seen when looking at AIDS-related deaths.

One of the weaknesses of cohort studies is that the selection of who starts or defers therapy is not random. This means that people who might have done poorly for other reasons would have delayed starting treatment, and thus skewed the results. The consortium’s analysis is unique so far in terms of cohort studies in that the researchers were able to follow a significant proportion of patients from well before they actually started treatment, which helped them filter out that kind of bias.

The authors conclude that their study’s results support the argument for starting treatment earlier and that at minimum, the current guidelines—beginning ARV treatment when CD4 counts drop to 350—should be rigorously followed.