Progesterone implants enhance SIV vaginal transmission and early virus load.
Simian immunodeficiency virus (SIV) can cross the intact vaginal epithelium to establish a systemic infection in macaques (mac). Using this SIVmac model, we found that subcutaneous progesterone implants, which could mimic hormonally based contraceptives, thinned the vaginal epithelium and enhanced SIV vaginal transmission 7.7-fold over that observed in macaques treated with placebo implants and exposed to SIV in the follicular phase of the menstrual cycle. Progesterone treatment also increased the number of SIV DNA-positive cells in the vaginal lamina propria as detected by in situ polymerase chain reaction analysis. Moreover, plasma viral RNA was elevated for the first three months in macaques with progesterone implants, and three of the progesterone-treated macaques developed relatively rapid disease courses. This study shows that SIV genital infection and disease course are enhanced by subcutaneous implants containing progesterone when compared with the rate of vaginal transmission in the follicular phase.
Marx
P A
PA
Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 10016, USA.
Spira
A I
AI
Gettie
A
A
Dailey
P J
PJ
Veazey
R S
RS
Lackner
A A
AA
Mahoney
C J
CJ
Miller
C J
CJ
Claypool
L E
LE
Ho
D D
DD
Alexander
N J
NJ
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D004198:Disease Susceptibility; D004343:Drug Implants; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D005260:Female; D005498:Follicular Phase; D007963:Leukocytes, Mononuclear / Q000821:virology; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D011533:Proviruses / Q000302:isolation & purification; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014621:Vagina / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D014766:Viremia / Q000821:virology*
D000914:Antibodies, Viral; D004279:DNA, Viral; D004343:Drug Implants; D011374:Progesterone