Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 208, Issue 8, Pages 1202-1211Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit311
Keywords
HIV antiretroviral therapy; early ART; T-cell activation; inflammation; HIV reservoir; HIV eradication; HIV cure
Categories
Funding
- National Institutes of Health (NIH) [R01 AI087145]
- NIH/National Institute of Allergy and Infectious Diseases [P01 AI071713, U01 AI41531]
- NIH [K24 AI069994]
- Delaney AIDS Research Enterprise [U19AI096109]
- UCSF/Gladstone Institute of Virology and Immunology Center for AIDS Research [P30 AI027763]
- NIH UCSF-CTSI [KL2TR000143]
- NIH Director's Pioneer Award Program, part of the NIH Roadmap for Medical Research [DPI OD003290]
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Background. CD4(+)/CD8(+) T-cell activation levels often remain elevated in chronic human immunodeficiency virus (HIV) infection despite initiation of antiretroviral therapy (ART). T-cell activation predicts early death 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 a cohort of patients with early HIV infection (<6 months duration since infection) we identified persons who started ART early (<6 months after infection) or later (>= 2 years after infection) and maintained >= 2 years of virologic suppression; at-risk HIV-negative persons were controls. We measured CD4(+)/CD8(+) T-cell activation (percent CD38(+)/HLA-DR+) and HIV reservoir size (based on 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%) than achieved with later ART (n = 32; mean, 28.8%; P = .009), although levels in early ART remained elevated relative to HIV-negative controls (P = .02). Early ART also predicted lower CD4(+) T-cell activation than with later ART (5.3% vs 7.5%; P = .06). Early ART predicted 4.8-fold lower DNA levels than achieved with later ART (P = .005), and lower cell-associated RNA levels (difference in signal-to-cutoff ratio (S/Co), 3.2; P = .035). Conclusions. ART initiation <6 months after infection is associated with lower levels of T-cell activation and smaller HIV DNA and RNA reservoir size during long-term therapy.
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