Nature Medicine
2, 1084 - 1089 (1996)
doi:10.1038/nm1096-1084
Progesterone implants enhance SIV vaginal transmission and early virus loadPreston A. Marx1, 2, 9, Alexander I. Spira1, 2, Agegnehu Gettie1, Peter J. Dailey3, Ronald S. Veazey4, Andrew A. Lackner4, C. James Mahoney5, Christopher J. Miller6, Lee E. Claypool7, David D. Ho1
& Nancy J. Alexander8
1Aaron Diamond AIDS Research Center, the Rockefeller University, 455 First Avenue, 7th Floor, New York, New York 10016, USA
2Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
3Chiron Corporation, Nucleic Acid Systems, 4560 Horton Street, D2, Emeryville, California 94608, USA
4Harvard Medical School, New England Regional Primate Research Center, One Pine Hill Drive, Southborough, Massachusetts 01772, USA
5New York University Medical Center, Laboratory for Experimental Medicine and Surgery in Primates, RR 1, Long Meadow Road, Tuxedo, New York 10987, USA
6California Regional Primate Research Center, University of California−Davis, Davis, California 95616, USA
7CONRAD Program, Eastern Virginia Medical School, 1611 North Kent Street, Suite 806, Arlington, Virginia 22209, USA
8Contraceptive Development Branch, National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Boulevard, Bethesda, Maryland 20892, USA
9Correspondence should be addressed to P.A.M. 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.
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