Early antiretroviral therapy reduces AIDS progression

Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS

Optimal timing of antiretroviral therapy initiation for individuals presenting with AIDS-related opportunistic infections has not been defined. A5164 was a randomized strategy trial of “ early antiretroviral therapy”—given within 14 days of starting treatment for acute opportunistic infection versus “deferred antiretroviral therapy”—given after treatment for acute opportunistic infection is completed. Randomization was stratified by presenting opportunistic infections and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) >or=50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 style="text-decoration: underline;">The early and deferred arms started antiretroviral therapy a median of 12 and 45 days after the start of treatment for opportunistic infections, respectively. AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early antiretroviral therapy arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27-0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30-0.92). The early antiretroviral therapy had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Early antiretroviral therapy resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred antiretroviral therapy. These results support the early initiation of antiretroviral therapy in patients presenting with acute AIDS-related opportunistic infections, absent major contraindications.

Editors’ note: Waiting to complete treatment for an opportunistic infection before initiating antiretroviral treatment in this USA/South Africa study was associated with a higher risk of HIV disease progression and/or death, with no safety or virological advantage. Concerns about toxicity, drug-drug interactions, immune reconstitution inflammatory syndrome, and adherence have made clinicians cautious about initiating antiretroviral treatment during treatment for opportunistic infections. However, as this study demonstrates, earlier antiretroviral treatment brings earlier improvement in immune responsiveness, which narrows the ‘window of vulnerability’ to additional HIV-related complications, preventing clinical progression.