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Depot medroxyprogesterone acetate (DMPA) enhances susceptibility and increases the window of vulnerability to HIV-1 in humanized mice.

ABSTRACT: The progestin-based hormonal contraceptive Depot Medroxyprogesterone Acetate (DMPA) is widely used in sub-Saharan Africa, where HIV-1 is endemic. Meta-analyses have shown that women using DMPA are 40% more likely than women not using hormonal contraceptives to acquire Human Immunodeficiency Virus (HIV-1). Therefore understanding how DMPA increases susceptibility to HIV-1 is an important public health issue. Using C57BL/6 mice and our previously optimized humanized mouse model (NOD-Rag1^tm1Mom Il2rg^tm1Wjl transplanted with hCD34-enriched hematopoietic stem cells; Hu-mice) where peripheral blood and tissues are reconstituted by human immune cells, we assessed how DMPA affected mucosal barrier function, HIV-1 susceptibility, viral titres, and target cells compared to mice in the diestrus phase of the estrous cycle, when endogenous progesterone is highest. We found that DMPA enhanced FITC-dextran dye leakage from the vaginal tract into the systemic circulation, enhanced target cells (hCD68+ macrophages, hCD4+ T cells) in the vaginal tract and peripheral blood (hCD45+hCD3+hCD4+hCCR5+ T cells), increased the rate of intravaginal HIV-1 infection, extended the window of vulnerability, and lowered vaginal viral titres following infection. These findings suggest DMPA may enhance susceptibility to HIV-1 in Hu-mice by impairing the vaginal epithelial barrier, increasing vaginal target cells (including macrophages), and extending the period of time during which Hu-mice are susceptible to infection; mechanisms that might also affect HIV-1 susceptibility in women.

SUBMITTER: Wessels JM

PROVIDER: S-EPMC7887257 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Depot medroxyprogesterone acetate (DMPA) enhances susceptibility and increases the window of vulnerability to HIV-1 in humanized mice.

Wessels Jocelyn M JM Nguyen Philip V PV Vitali Danielle D Mueller Kristen K Vahedi Fatemeh F Felker Allison M AM Dupont Haley A HA Bagri Puja P Verschoor Chris P CP Deshiere Alexandre A Mazzulli Tony T Tremblay Michel J MJ Ashkar Ali A AA Kaushic Charu C

Scientific reports 20210216 1

The progestin-based hormonal contraceptive Depot Medroxyprogesterone Acetate (DMPA) is widely used in sub-Saharan Africa, where HIV-1 is endemic. Meta-analyses have shown that women using DMPA are 40% more likely than women not using hormonal contraceptives to acquire Human Immunodeficiency Virus (HIV-1). Therefore understanding how DMPA increases susceptibility to HIV-1 is an important public health issue. Using C57BL/6 mice and our previously optimized humanized mouse model (NOD-Rag1<sup>tm1Mo ...[more]

PMID: 33594113

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Project description:ObjectivesExpanding contraceptive options through self-injection may improve access and confidentiality. There are few published studies on contraceptive self-injection in sub-Saharan Africa and none in West Africa, a region with high unmet need. This study was performed to assess feasibility of subcutaneous DMPA self-injection in Senegal; objectives were to (1) measure the proportion of participants who self-injected competently 3 months after training, (2) measure the proportion who self-injected on time (defined conservatively as within 7 days of reinjection date), and (3) assess acceptability of self-injection.Study designIn this prospective cohort study, 378 women aged 18-49 years were trained to self-inject by study nurses. Three months later, women returned unprompted to the clinic to self-inject, and technique and visit timing were evaluated. Women continuing with a third self-injection were followed up at home after their next scheduled injection date. At each interaction, participants were interviewed to learn about their experience; additional questions during the final home visit focused on storage and disposal practices, and acceptability.ResultsAmong the 337 participants followed up 3 months post-training, 310 self-injected, and 87% did so competently. Factoring in women who declined to self-inject, electing to have the provider administer the injection instead, a total of 80% [95% confidence interval (CI)=75-84%] self-injected competently 3 months post-training, and 84% [95% CI=80-88%] reinjected on time, while 72% [95% CI=67-77%] were both on time and competent. The vast majority (93%) expressed a desire to continue.ConclusionsSelf-injection is feasible and acceptable among most study participants in Senegal.ImplicationsThese first research results on contraceptive self-injection in West Africa indicate initial feasibility and acceptability of the practice. Results underscore the importance of designing self-injection programs that empower and support women, including those with limited education.

Dataset Information

Depot medroxyprogesterone acetate (DMPA) enhances susceptibility and increases the window of vulnerability to HIV-1 in humanized mice.

Publications

Depot medroxyprogesterone acetate (DMPA) enhances susceptibility and increases the window of vulnerability to HIV-1 in humanized mice.

Similar Datasets

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