std-hiv-aids-2017-posters-accepted-abstracts

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International Journal of HIV and AIDS research

International Conference on

Sexually Transmitted Diseases, AIDS and Parasitic Infections

Parasitology, Infectious Diseases, STDs and STIs

September 21-22, 2017 San Antonio, TX, USA

Increased HIV-1 acquisition by Depo-Provera unlike Nur-Isterate involves increased

HIV-1 replication and CCR5 co-receptor levels

Janet P Hapgood, Roslyn M Ray, Michelle F Maritz, Chanel Avenant, Michele Tomasicchio

and

Zephne van der Spuy

University of Cape Town, South Africa

pidemiological data show a significant association between usage of the progestin-only injectable

contraceptive depo-medroxyprogesterone acetate (DMPA, Depo-Provera) and increased HIV-1 acquisition.

No such association is shown for the progestin-only injectable contraceptive norethisterone (NET) enanthate

(Nur-Isterate). Whether this association for DMPA is due to confounding factors inherent in clinical studies is

highly controversial and a critical issue for women’s health, especially in developing countries with high DMPA

usage and high HIV-1 prevalence and incidence. Using novel receptor and cell biology approaches to this clinical

problem, we investigated the direct actions of these progestins on tissue and cellular models

ex vivo

, towards

elucidation of biological mechanisms to explain the clinical data. We show for the first time that MPA, unlike

NET, significantly increases HIV-1 replication in human cervical explant tissue at concentrations detected in

the serum of DMPA users. These results together with results in peripheral blood mononuclear cells and an

indicator cell line support a mechanism whereby MPA, acting via the glucocorticoid receptor (GR), increases

HIV-1 replication in genital tract tissue. We discuss the mechanisms of this effect. Our data offer novel insights

and a plausible biological mechanism for more informed choice of contraception for women at high risk of HIV-1

infection with significant potential impact on contraception policy and HIV-1 prevention.