The fact that we did not find an increased risk of early adverse outcomes among those who had OIs that were diagnosed at ART initiation is similar to results from studies finding no increased risk of early mortality in patients with known pulmonary TB at ART initiation and further supports efforts to detect and treat these conditions at the time of starting ART. The high proportion of initial outcomes that were OIs also warrants further consideration of ‘‘unmasking’’ immune reconstitution inflammatory syndrome as a potentially important mechanism of early clinical deterioration. Although recent data from sub-Saharan Africa indicate that fatal IRIS is rare, patients may die before excessive inflammation can be proven, particularly when inflammation occurs very early after ART initiation and when studies are retrospective. Therefore further evaluation of the role of very early inflammation in early morbidity and mortality is Verdinexor warranted. We did not prospectively grade drug toxicity, but many ART drugs including zidovudine and nevirapine, which were initiated by most and nearly half of the patients in this study, respectively, have potentially fatal toxicities that could cause early mortality despite and perhaps even due to high levels of adherence. Severe drug toxicity in treatment centers in Africa is well-described, and both zidovudine-associated anemia and lactic acidosis may be more common in treated HIV-infected Africans. More broadly, clarifying the mechanisms by which adverse outcomes occur in the setting of high adherence and virologic suppression, of which drug toxicity is one, should be pursued. Strengths of this study include a novel focus on early adherence data using prospective prescription information,KPT330 Selinexor careful ascertainment of data on incident OIs, active patient tracing to determine outcomes, the sub-Saharan African setting and the availability of routinely-collected viral load results, which enhanced our evaluation. Inclusion of patients who initiated but never returned for an ART refill in the primary analysis is another strength of the study. Given that risk of early mortality after ART initiation in resource-limited settings is highest very early after starting ART, excluding individuals who are lost to follow-up or die early after ART initiation excludes precisely those to whom the study question is most relevant.