Progestin-based contraceptive suppresses cellular immune responses in SHIV-infected rhesus macaques.
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.
Trunova
Nataliya
N
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave, 7th Floor, New York, NY 10016, USA.
Tsai
Lily
L
Tung
Stephanie
S
Schneider
Eric
E
Harouse
Janet
J
Gettie
Agegnehu
A
Simon
Viviana
V
Blanchard
James
J
Cheng-Mayer
Cecilia
C
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
D003271:Contraceptive Agents, Female; D011372:Progestins; D007371:Interferon-gamma; D017258:Medroxyprogesterone Acetate