Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial.
BACKGROUND
Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined.


RESULTS
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.


BACKGROUND
ClinicalTrials.gov NCT00055120.
Stanford University AIDS Clinical Trials Unit, Stanford University, Stanford, California, United States of America. azolopa@stanford.edu
Andrew
A
Zolopa
Janet
J
Andersen
William
W
Powderly
Alejandro
A
Sanchez
Ian
I
Sanne
Carol
C
Suckow
Evelyn
E
Hogg
Lauren
L
Komarow
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D044966:Anti-Retroviral Agents