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The optimum time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-1-infected patients with serious opportunistic infections has, until recently, been undefined. Initiation of early ART is associated with the risk of the immune reconstitution inflammatory syndrome (IRIS), complex drug interactions, and a high pill burden, but deferral risks advancing immunosuppression and mortality. A number of recent clinical trials have now better informed this issue. Two studies have shown benefits associated with earlier ART initiation [1, 2]. A study of patients with a range of opportunistic and bacterial infections, not including tuberculosis (TB), demonstrated that early ART initiation (median, 12 days after diagnosis of infection) resulted in fewer events or deaths related to AIDS progression (a combined secondary end point), compared with initiation of ART after acute infection treatment (median, 45 days after diagnosis of infection) [1]. A subanalysis of this study showed that, in patients with fungal infections, there was also a significant reduction in AIDS progression and death associated with early initiation. In TB, patients who started ART during TB treatment had reduced mortality, compared with those who deferred ART until TB treatment was completed [2]. The pendulum seemed to be swinging in favor of earlier ART initiation in the context of opportunistic infections. However, in a study of patients with TB meningitis, there was no difference in mortality between patients who started ART at the same time as TB treatment and those who deferred ART for 2 months, but there were significantly more severe adverse events in the first 2 months of treatment in the immediate ART arm [3].

Issue Section:
HIV/AIDS > Editorial Commentaries
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