Title | Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Zolopa A, Andersen J, Powderly W, Sanchez A, Sanne I, Suckow C, Hogg E, Komarow L |
Journal | PLoS One |
Volume | 4 |
Issue | 5 |
Pagination | e5575 |
Date Published | 2009 |
ISSN | 1932-6203 |
Keywords | Acquired Immunodeficiency Syndrome, Adolescent, Adult, Anti-Retroviral Agents, Disease Progression, Drug Administration Schedule, Female, HIV Infections, Humans, Male, Time Factors, Treatment Outcome, Young Adult |
Abstract | BACKGROUND: Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. METHODS AND FINDINGS: A5164 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) >or=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. CONCLUSIONS: Early 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 REGISTRATION: ClinicalTrials.gov NCT00055120. |
DOI | 10.1371/journal.pone.0005575 |
Alternate Journal | PLoS ONE |
PubMed ID | 19440326 |
PubMed Central ID | PMC2680972 |
Grant List | AI38858 / AI / NIAID NIH HHS / United States AI68634 / AI / NIAID NIH HHS / United States AI68636 / AI / NIAID NIH HHS / United States |