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PLoS One. 2019 Aug 22;14(8):e0221181. doi: 10.1371/journal.pone.0221181. eCollection 2019.

Effects of the levonorgestrel-containing intrauterine device, copper intrauterine device, and levonorgestrel-containing oral contraceptive on susceptibility of immune cells from cervix, endometrium and blood to HIV-1 fusion measured ex vivo.

Author information

1
Gladstone Institute of Virology and Immunology, San Francisco, California, United States of America.
2
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
3
Department of Urology, University of California San Francisco, San Francisco, California, United States of America.
4
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, United States of America.
5
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, San Diego, California, United States of America.
6
Departments of Clinical Pharmacy and Medicine, University of California San Francisco, San Francisco, California, United States of America.
7
Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, United States of America.

Abstract

Globally, HIV/AIDS is a leading cause of morbidity worldwide among reproductive-aged cisgender women, highlighting the importance of understanding effects of contraceptives on HIV-1 risk. Some observational studies suggest there may be an increased risk of HIV-1 acquisition among women using the long-acting injectable progestin contraceptive, depo-medroxyprogesterone acetate. The potential mechanism of this susceptibility is unclear. There are few data on the role of the upper female reproductive tract in HIV-1 transmission, and the mechanisms of HIV-1 infection are likely to differ in the upper compared to the lower reproductive tract due to differences in tissue composition and variable effects of sex steroids on mucosal immune cell distribution and activity. In this study, we measured the susceptibility of mucosal immune cells from the upper female reproductive tract to HIV-1 entry using the virion-based HIV-1 fusion assay in samples from healthy female volunteers. We studied 37 infectious molecular clones for their ability to fuse to cells from endometrial biopsies in three participants and found that subtype (B or C) and origin of the virus (transmitted founder or chronic control) had little influence on HIV-1 fusion susceptibility. We studied the effect of contraceptives on HIV-1 susceptibility of immune cells from the cervix, endometrium and peripheral blood by comparing fusion susceptibility in four groups: users of the copper intrauterine device (IUD), levonorgestrel-containing oral contraceptive, levonorgestrel-containing IUD and unexposed controls (n = 58 participants). None of the contraceptives was associated with higher rates of HIV-1 entry into female reproductive tract cells compared to control samples from the mid-luteal phase.

Conflict of interest statement

SA is on the Board of Directors of One Heart World Wide, an NGO that does safe motherhood work in Nepal, is on the Advisory Board of Center for AIDS Research at University of California San Diego and has a research grant from the Society of Family Planning to study early initiation of postpartum contraception. BLS receives funding from the National Institutes of Health (NIAID R01 AI057020; NIDDK R01 DK108350; NCI P30 CA093373) and research contracts from Gilead Sciences. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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