title: Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.
abstract: BACKGROUND
  Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs).
  
  
  RESULTS
  We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden.
  
  
  CONCLUSIONS
  Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.
authors.affiliation: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cellerai
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.forename: Hans
authors.initials: H
authors.lastname: Stauss
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Geretti
authors.forename: Anne
authors.initials: A
authors.lastname: Carroll
authors.forename: Thynn
authors.initials: T
authors.lastname: Yee
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ainsworth
authors.forename: Ian
authors.initials: I
authors.lastname: Williams
authors.forename: John
authors.initials: J
authors.lastname: Sweeney
authors.forename: Andrew
authors.initials: A
authors.lastname: Freedman
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Sabine
authors.initials: S
authors.lastname: Kinloch-de Loes
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D054301:gag Gene Products, Human Immunodeficiency Virus; D054353:Perforin