title: HIV-1 p24 may persist during long-term highly active antiretroviral therapy, increases little during short treatment breaks, and its rebound after treatment stop correlates with CD4(+) T cell loss.
abstract: The dynamics of HIV-1 RNA during structured treatment interruptions (STIs) are well established, but little is known about viral proteins like p24. We studied 65 participants of an STI trial. Before the trial, continuous highly active antiretroviral therapy (HAART) had suppressed their viral load to <50 copies/mL during 6 months. They then interrupted HAART during weeks 1 through 2, 11 through 12, 21 through 22, 31 through 32, and 41 through 52. The p24 was measured by boosted enzyme-linked immunosorbent assay of plasma pretreated by efficient virus disruption and heat denaturation. At time point 0, p24 was measurable in 22 patients (34%), who had maintained a viral load <50 copies/mL for 25.4 months (median, range: 6.2-38.9 months) under HAART. Viral rebounds during 2-week STIs led to a mean p24 increase of only 0.08 to 0.19 log10 (ie, 20%-60%). Pre-HAART viral load and p24 at time 0 independently predicted p24 rebounds during the 4 2-week STIs. The p24 at time 0 and HIV-1 RNA rebound during weeks 41 through 52 independently determined the concomitant p24 rebound. An increase of p24 but not viral load during the first 8 weeks of the long STI correlated significantly with concomitant CD4(+) T cell loss. Persisting p24 despite successful HAART may reflect virus replication in reservoirs not represented by plasma viral load and has implications for the concept of therapeutic vaccination.
authors.affiliation: Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. jschupb@immv.unizh.ch
authors.forename: Jörg
authors.initials: J
authors.lastname: Schüpbach
authors.forename: Huldrych
authors.initials: H
authors.lastname: Günthard
authors.forename: Beda
authors.initials: B
authors.lastname: Joos
authors.forename: Marek
authors.initials: M
authors.lastname: Fischer
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Tomasik
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Luc
authors.initials: L
authors.lastname: Perrin
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D016655:HIV Core Protein p24