title: Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size.
abstract: 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.
authors.affiliation: HIV/AIDS Division, San Francisco General Hospital.
authors.forename: Vivek
authors.initials: V
authors.lastname: Jain
authors.forename: Wendy
authors.initials: W
authors.lastname: Hartogensis
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Hiroyu
authors.initials: H
authors.lastname: Hatano
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Lorrie
authors.initials: L
authors.lastname: Epling
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pilcher
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D004197:Disease Reservoirs / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral
keywords: HIV antiretroviral therapy; HIV cure; HIV eradication; HIVreservoir; T-cell activation; early ART; inflammation