title: Progestin-based contraceptive suppresses cellular immune responses in SHIV-infected rhesus macaques.
abstract: Nine rhesus macaques in groups of three received a single dose of the injectable progestin-based contraceptive Depo-Provera 5 weeks prior to challenge intravaginally with varying doses of a mixture of the pathogenic CXCR4 (X4)-SHIV(SF33A) and CCR5 (R5)-SHIV(SF162P3) isolates. As controls, seven Depo-naive animals were inoculated once with a high-dose of the mixed inoculum. Irrespective of inoculum dose, acute viremia was higher in the Depo-treated than in the Depo-naive animals. Further, genetic complexity of the replicating virus was greater and replication of the X4 virus was favored in dually infected animals treated with Depo-Provera. Analysis of cellular immune responses revealed slower response rates in virus-specific IFN-gamma production to SIV Gag in the Depo-treated macaques. The immunosuppressive effect of Depo-Provera on mounting an antiviral cellular immune response may account for the increase viral burden and diversity, and the predominance of X4 virus replication in SHIV infected macaques that were administered the progestin-based contraceptive.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave, 7th Floor, New York, NY 10016, USA.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Trunova
authors.forename: Lily
authors.initials: L
authors.lastname: Tsai
authors.forename: Stephanie
authors.initials: S
authors.lastname: Tung
authors.forename: Eric
authors.initials: E
authors.lastname: Schneider
authors.forename: Janet
authors.initials: J
authors.lastname: Harouse
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Viviana
authors.initials: V
authors.lastname: Simon
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cheng-Mayer
mesh_terms: D000818:Animals; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000494:pharmacology; D004198:Disease Susceptibility; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008253:Macaca mulatta; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000494:pharmacology; D011372:Progestins / Q000008:administration & dosage / Q000494:pharmacology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D003271:Contraceptive Agents, Female; D011372:Progestins; D007371:Interferon-gamma; D017258:Medroxyprogesterone Acetate