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Sabes: Randomization to Immediate ART Initiation in Acute and Recent HIV Improves Early Clinical and Immunologic Outcomes
132 Pages Posted: 25 Jun 2019
More...Abstract
Background: There are few clinical trial data to inform recommendations about management of acute HIV. In addition to the demonstrated public health benefits on reducing transmission, clinical, virologic and immunologic benefits of early treatment after HIV infection have been recognized, but the optimal window to maximize these benefits remains unclear.
Methods: Adult men who have sex with men and transgender women with acute (HIV-antibody negative/HIV-1 RNA positive) or recent (confirmed negative HIV-antibody or RNA test within three months) HIV infection participated in an open label randomized study in Lima, Peru, to start antiretroviral therapy (ART) immediately vs defer by 24 weeks (trial registered with ClinicalTrials.gov, number NCT01815580). Clinical, virologic and immunologic outcomes by treatment arm and days since estimated date of detectible infection (EDDI) were evaluated.
Findings: Two-hundred and sixteen participants were randomly assigned, 105 to the immediate arm and 116 to deferred arm. The incidence rate of non-ART-related adverse events was lower in the immediate vs deferred arm (83 vs 123 per 100 person-years, Hazard Ratio 0.67; p=0.02); the difference was dominated by fewer infections in those treated immediately. After 24 weeks of administered ART, between-group differences in CD4/CD8 cell ratio lessened (p=0.09 overall), but the difference between those treated ≤30 days from EDDI (median 1.03, IQR 0.84, 1.37), and those treated >90 days (median 0.88, IQR 0.61, 1.11) remained significant, p=0.02. Principal components analysis of 20 biomarkers of immune activation demonstrated distinct patterns between those starting ART >90 days from EDDI vs those who started within 30 or 90 days (both p<0.001), but those starting ART within 30 or 90 days were indistinct from each other after 24 weeks of ART.
Interpretation: This study provides evidence to strengthen World Health Organization recommendations to explicitly include acute HIV in recommendations for universal ART initiation.
Trial Registration: NCT01815580.
Funding Statement: Funding for this project was supported by the National Institute on Drug Abuse R01DA032106 (AD, JRL, JS); National Institute of Allergy and Infectious Diseases K23AI129659 (RBI).
Declaration of Interests: Authors declare no conflicts of interest.
Ethics Approval Statement: This study was approved by the Institutional Review Board at the Fred Hutchinson Cancer Research Center and the Institutional Bioethics Committee at Asociación Civil Impacta Salud y Educación. All study participants provided written consent in Spanish, their native language, to participate in the study. Implementation of the study was authorized by the Peruvian National Institute of Health.
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