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Page 49
http://parasitology.cmesociety.com|
http://std.cmesociety.comInternational 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
E
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.
janet.hapgood@uct.ac.za