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Current guidelines do not clarify when HIV-positive patients with a newly diagnosed opportunistic infection (OI) should initiate antiretroviral therapy (ART; JW AIDS Clin Care Mar 30 2009). Is earlier better?
In the ACTG A5164 trial, researchers enrolled 282 patients within 14 days after they had started treatment for a proven or presumptive OI (JW AIDS Clin Care Mar 9 2009). Participants were then randomized to receive ART either within 48 hours after enrollment (early group) or between 4 and 32 weeks after enrollment (delayed group). The study-provided ART regimen was lopinavir/ritonavir, FTC, tenofovir, and stavudine, but use of any ART combination approved by the FDA for initial treatment of HIV infection was allowed. All patients in the early group and 91% of those in the delayed group actually initiated ART (at a median of 12 and 45 days, respectively, after starting treatment for the OI).
Of the entire cohort, 85% were men, 70% had baseline CD4 counts <50 cells/mm3, and more than 90% were ART-naive. The most common OIs were Pneumocystis jirovecii pneumonia (PCP; 63% of subjects), cryptococcal meningitis (12%), and serious bacterial infections (12%); 33% had multiple OIs. Only 5% of patients had toxoplasmosis, and only 2% had Mycobacterium avium complex.
At 48 weeks after enrollment, the incidence of AIDS progression or death was significantly lower in the early-ART group than in the delayed-ART group (14% vs. 24%), and the early group’s time to AIDS progression or death was significantly longer. Mean viral load and CD4-cell count at 48 weeks did not differ significantly between the groups. The 20 confirmed cases of immune reconstitution inflammatory syndrome (IRIS; 8 in the early group, 12 in the delayed group) developed a median of 33 days after ART initiation. IRIS incidence did not differ significantly between participants who received steroids and those who did not.
Zolopa AR et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: A multicenter randomized strategy trial. PLoS One 2009 May 18; 4:e5575.
Comment
This study’s most significant limitation is that PCP was such a predominant OI, with other OIs not represented in large numbers (although this predominance likely reflects the epidemiology of OIs in the era of combination ART). Nevertheless, the findings add to accumulating evidence that early initiation of ART may provide benefit in the setting of most OIs, possibly by preventing morbidity and mortality in the first 6 months related to the development of other AIDS-defining illnesses. Of course, early ART clearly makes sense for patients with OIs for which there is no known effective treatment. Notably, 9% of patients in the delayed-treatment group never started ART even though it was indicated, suggesting a lost opportunity to receive care.