Abstract
BackgroundOptimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined.Methods and FindingsA5164 was a randomized strategy trial of “early ART” - given within 14 days of starting acute OI treatment versus “deferred ART” - given after acute OI treatment is completed. Randomization was stratified by presenting OI 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) ≥50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS.282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively.The difference in the primary endpoint did not reach statistical significance: 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 ART 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 ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events.ConclusionsEarly ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications.Trial RegistrationClinicalTrials.gov NCT00055120
Highlights
Over the past decade there has been remarkable progress in the treatment of HIV-1 infection
Early antiretroviral therapy (ART) resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART
These results support the early initiation of ART in patients presenting with acute AIDS-related opportunistic infections (OIs), absent major contraindications
Summary
Over the past decade there has been remarkable progress in the treatment of HIV-1 infection. [4,5,6] Despite these advances, mortality rates remain unacceptably high in populations with poor access to health care services such as communities of color, young adults, and poor rural and inner-city dwellers [7,8,9,10,11,12] who frequently first enter HIV care with acute AIDS-related opportunistic infections (OIs). Concurrent treatment of the OI and HIV might result in higher morbidity and/or mortality by increasing toxicity of treatment, increasing drug-drug interactions, decreasing adherence to the OI regimen, and increasing the frequency of immune reconstitution and inflammatory syndrome (IRIS) reactions. Concurrent treatment might decrease patient morbidity/mortality by restoring pathogen-specific immune responses and speeding immune reconstitution. Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined
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