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Randomized Controlled Trial
. 2009;4(5):e5575.
doi: 10.1371/journal.pone.0005575. Epub 2009 May 18.

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

Andrew Zolopa  1 , Janet Andersen, William Powderly, Alejandro Sanchez, Ian Sanne, Carol Suckow, Evelyn Hogg, Lauren Komarow
Affiliations
Randomized Controlled Trial

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

Andrew Zolopa et al. PLoS One. 2009.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Study Subject Enrollment and Discontinuation.
Figure 2
Figure 2. Time to ART initiation from the start of OI/BI treatment.
Early arm median 12 days [IQR 9–13 days]; Deferred arm median 45 days [IQR 41–55 days].
Figure 3
Figure 3. Time to AIDS progression or death.
HR = 0.53 Early versus Deferred ART [95%CI 0.30–0.92 p = 0.023].
Figure 4
Figure 4. AIDS Progression/Death by entry diagnoses given as log Odds ratios (with 95%CI) with OR <1.0 favoring early versus deferred ART.
Total, fungal and CD4<50 categories represent significance at p<0.05. (Fungal Infections include cryptococcal infections and histoplasmosis).
Figure 5
Figure 5. Time to CD4>50 cells/mm3; Early ART median time 4.0 weeks (IQR 0–5.0 weeks) versus deferred ART median time 8.1 weeks (IQR 0–12.7 weeks).
Right side graph: Time to CD4>100 cells/mm3; Early ART median time 4.3 weeks (IQR 4.0–23.6 weeks) versus Deferred ART median time 12.1 weeks (IQR 8.6–28.1 weeks) (p<0.001 for both comparisons).
See this image and copyright information in PMC

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