Progestin-based contraceptive suppresses cellular immune responses in SHIV-infected rhesus macaques

• Published in: Virology (New York, N.Y.) Vol. 352; no. 1; pp. 169 - 177
• Main Authors: Trunova, Nataliya, Tsai, Lily, Tung, Stephanie, Schneider, Eric, Harouse, Janet, Gettie, Agegnehu, Simon, Viviana, Blanchard, James, Cheng-Mayer, Cecilia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-08-2006
• Subjects: Animals; Contraceptive Agents, Female - administration & dosage; Contraceptive Agents, Female - pharmacology; Disease Susceptibility; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; HIV-1 - pathogenicity; Hormonal contraceptive use; Humans; Interferon-gamma - biosynthesis; Lymphocyte Activation - drug effects; Macaca mulatta; Medroxyprogesterone Acetate - administration & dosage; Medroxyprogesterone Acetate - pharmacology; Progestins - administration & dosage; Progestins - pharmacology; Replication; SHIV susceptibility; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - virology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - pathogenicity; T-Lymphocytes - immunology; Viral Load; Virus Replication; Replication; SHIV susceptibility; Hormonal contraceptive use
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.04.004

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-γ 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.