title: Interleukin-7 promotes HIV persistence during antiretroviral therapy.
abstract: HIV persists in latently infected memory CD4(+) T cells during antiretroviral therapy (ART). When administered to HIV-infected subjects receiving suppressive ART, interleukin-7 (IL-7) increases the number of CD4(+) T cells by promoting their survival and proliferation. However, little is known about the impact of IL-7 on HIV persistence during ART. By isolating large numbers of CD4(+) T cells from HIV-infected subjects, we demonstrate that IL-7 enhances viral production in productively infected cells but does not disrupt viral latency in latently infected cells. When administered to virally suppressed subjects, IL-7 led to the rapid proliferation of memory CD4(+) T cells, which resulted in a 70% increase in the absolute number of circulating CD4(+) T cells harboring integrated HIV DNA 4 weeks after therapy. The genetic diversity of the viral reservoir increased transiently in the majority of the subjects studied before returning to baseline values. Altogether, our results indicate that IL-7 promotes the mechanisms of HIV persistence during ART by enhancing residual levels of viral production and inducing proliferation of latently infected cells, and suggest that IL-7 does not represent a suitable candidate therapeutic strategy for HIV eradication. This trial was registered at www.clinicaltrials.gov as #NCT00099671 (AIDS Clinical Trials Group protocol 5214).
authors.affiliation: Vaccine and Gene Therapy Institute Florida, Port St. Lucie, FL 34987, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Vandergeeten
authors.forename: Rémi
authors.initials: R
authors.lastname: Fromentin
authors.forename: Sandrina
authors.initials: S
authors.lastname: DaFonseca
authors.forename: Mariam B
authors.initials: MB
authors.lastname: Lawani
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Moti
authors.initials: M
authors.lastname: Ramgopal
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sékaly
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D014644:Genetic Variation / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology* / Q000494:pharmacology; D017735:Virus Latency / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; C508605:IL7 protein, human; D015851:Interleukin-7