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NEW THIS THURSDAY: ANTIRETROVIRAL THERAPY INITIATED WITHIN SIX MONTHS OF HIV INFECTION IS ASSOCIATED WITH LOWER T-CELL ACTIVATION AND SMALLER HIV RESERVOIR SIZE

Wednesday, 17th of July 2013

 

• ANTIRETROVIRAL THERAPY INITIATED WITHIN SIX MONTHS OF HIV INFECTION IS ASSOCIATED WITH LOWER T-CELL ACTIVATION AND SMALLER HIV RESERVOIR SIZE

 

J Infect Dis. (2013) doi: 10.1093/infdis/jit311 First published online: July 12, 2013

Vivek Jain1, Wendy Hartogensis1, Peter Bacchetti2, Peter W. Hunt1, Hiroyu Hatano1,

Elizabeth Sinclair3, Lorrie Epling3, Tzong-Hae Lee4, Michael P. Busch4, Joseph M. McCune3,

Christopher D. Pilcher1, Frederick M. Hecht1 and Steven G. Deeks1

+ Author Affiliations

1HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco (UCSF), USA

2Dept of Epidemiology and Biostatistics, UCSF, San Francisco, USA

3Division of Experimental Medicine, University of California, San Francisco (UCSF), USA

4Blood Systems Research Institute, San Francisco, CA, USA

Corresponding author: Vivek Jain, MD, MAS, HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, UCSF Box 0874, San Francisco, CA 94143-0874., Tel: (415) 326-3402; Fax: (415) 476-6953; Email: vivek.jain@ucsf.edu.

Abstract below; full text available to journal subscribers

Background. CD4+/CD8+ T-cell activation levels often remain elevated despite HIV antiretroviral therapy (ART) initiated during chronic infection. T-cell activation predicts early mortality and blunted CD4+ T-cell recovery during ART, and may affect persistent HIV reservoir size. We investigated whether very early ART initiation is associated with lower on-therapy immune activation and HIV persistence.

Methods. From an early HIV infection (<6 months) cohort, we identified persons who started ART early (<6 months after infection) or later (≥2 years) and maintained ≥2 years of virologic suppression; at-risk HIV-negative persons were controls. We measured CD4+/CD8+ T-cell activation (%CD38+/HLA-DR+) and HIV reservoir size (via HIV DNA and cell-associated RNA levels).

Results. In unadjusted analyses, early ART predicted lower on-therapy CD8+ T-cell activation (n=34, mean 22.1%) vs. later ART (n=32, mean 28.8%, p=0.009), although levels in early ART remained elevated vs. HIV-negative controls (p=0.02). Early ART also predicted lower CD4+ T-cell activation vs. later ART (5.3% vs. 7.5%, p=0.061). Early ART predicted 4.8-fold lower DNA levels (p=0.0045) and 3.2 signal-to-cutoff ratio (S/Co) unit lower cell-associated RNA levels (p=0.035) vs. later ART.

Conclusions. ART initiation <6 months following infection is associated with lower T-cell activation and smaller HIV DNA and RNA reservoir size during long-term therapy.

Received November 28, 2012.

Revision received March 31, 2013.

Accepted April 12, 2013.

© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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EDITORIAL:

Timothy J. Henrich andRajesh T. Gandhi

Early Treatment and HIV-1 Reservoirs: A Stitch in Time? J Infect Dis. jit307 first published online July 12, 2013 doi:10.1093/infdis/jit307