Dataset Information

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

ACCESS DATA

Publications

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

Similar Datasets

Project description:Since the introduction of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) in 2018, Malawi has achieved national coverage of trained providers in the public sector and steady increases in uptake of DMPA-SC. However, the rate of clients opting to self-inject DMPA-SC has remained lower than early acceptability studies suggested. Providers play an instrumental role in building client confidence to self-inject through counselling/training. This cross-sectional qualitative study explored the perspectives of providers and injectable clients on the integration of self-injection into contraceptive counselling, to identify best practices and potential gaps. The study was conducted at public sector sites in three districts (Nkhotakota, Mzimba South, Zomba) in Malawi. In-depth interviews were conducted with provider-administered injectable clients, self-injecting clients, and DMPA-SC trained providers. All providers interviewed reported successfully integrating self-injection into their approach. During group health education sessions, some providers reported focusing on benefits of self-injection to spark interest in the method, and then follow that up with more in-depth information during individual counselling. Due to time pressures, a minority of providers reported replacing individual counselling with small-group counselling and limited use of elements such as visualizations and demonstrations. Most providers skipped client practice on inanimate objects, feeling this was either not necessary or inappropriate given stock constraints. Self-injection clients tended to credit their decision to take up SI to receiving lengthy, comprehensive counselling/training, often inclusive of reassuring messages, visualizations, demonstrations and sometimes repeated trainings over time. Provider-administered clients tended to credit their lack of uptake of self-injection to fear and lack of confidence, often blaming themselves instead of the quality of their counselling/training-even while many felt their counselling/training had been rushed or incomplete. Providers should be supported to overcome time- and resource-pressures to invest in counselling/training best practices, to ensure sufficient support is provided to clients interested in self-injection.

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

OmicsDI is part of the ELIXIR infrastructure

Tweets