title: Antiretroviral treatment start-time during primary SIV(mac) infection in macaques exerts a different impact on early viral replication and dissemination.
abstract: BACKGROUND
  The time of infection is rarely known in human cases; thus, the effects of delaying the initiation of antiretroviral therapy (ART) on the peripheral viral load and the establishment of viral reservoirs are poorly understood.
  
  
  RESULTS
  Six groups of macaques, infected intravenously with SIV(mac251), were given placebo or antiretroviral therapy to explore reservoir establishment; macaques were treated for 2 weeks, with treatment starting 4 hours, 7 or 14 days after infection. Viral replication and dissemination were measured in the gut (rectum), in the lung and in blood and lymphoid tissues (peripheral lymph nodes), by quantifying viral RNA, DNA and 2LTR circles. We used immunohistochemistry (CD4 and CD68) to assess the impact of these treatments on the relative amount of virus target cells in tissue. Treatment that was started 4 hours post-infection (pi) decreased viral replication and dissemination in blood and tissue samples, which were assessed on day 14 (RNA/DNA/2LTR circles). The virus remained detectable and lymphoid tissues were activated in LN and the gut in both placebo- and ART-treated animals. Viral RNA in plasma continued to be lower in macaques treated seven days after infection; however, this was not the case for viral DNA in peripheral blood mononuclear cells. There was a small but significant difference in RNA and DNA levels in tissues between placebo- and ART-treated animals on day 21. When started 14 days after infection, treatment resulted in a limited decrease in the plasma viral load.
  
  
  CONCLUSIONS
  Treatment that was started 4 hours after infection significantly reduced viral replication and dissemination. When started 7 days after infection, it was of slight virological benefit in peripheral blood and in tissues, and treatment was even less effective if started 14 days pi. These data favor starting ART no longer than one week after intravenous SIV(mac251) exposure.
authors.affiliation: Division of ImmunoVirology (SIV), Institute of Emerging Diseases and Innovative Therapies (IMETI), CEA, Fontenay-aux-Roses, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sellier
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Mannioui
authors.forename: Olivier
authors.initials: O
authors.lastname: Bourry
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.forename: Benoit
authors.initials: B
authors.lastname: Delache
authors.forename: Patricia
authors.initials: P
authors.lastname: Brochard
authors.forename: Julien
authors.initials: J
authors.lastname: Calvo
authors.forename: Sophie
authors.initials: S
authors.lastname: Prévot
authors.forename: Pierre
authors.initials: P
authors.lastname: Roques
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D002465:Cell Movement; D008251:Macaca / Q000276:immunology / Q000821:virology*; D009928:Organ Specificity; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule