Medroxyprogesterone acetate concentrations among HIV-infected depot-medroxyprogesterone acetate users receiving antiretroviral therapy in Lilongwe, Malawi.
Ontology highlight
ABSTRACT: Objective
To compare medroxyprogesterone acetate (MPA) concentrations between HIV-positive women on antiretroviral therapy (ART) and HIV-negative women initiating depot medroxyprogesterone (DMPA) injectable.Study design
Secondary analysis of 28 HIV-positive women on non-nucleoside reverse transcriptase inhibitor-containing ART regimens and 10 HIV-negative women randomized to initiate DMPA in a clinical trial of progestin contraception in Malawi.Results
MPA concentrations were significantly lower among HIV-positive women on ART, compared with HIV-negative women, at week 4 and week 13 (p=.03 for both), but not at day 3 or week 26 post-DMPA initiation.Conclusions
Antiretroviral medications may affect MPA metabolism in HIV-positive African women.
SUBMITTER: Zia Y
PROVIDER: S-EPMC7245365 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Medroxyprogesterone acetate concentrations among HIV-infected depot-medroxyprogesterone acetate users receiving antiretroviral therapy in Lilongwe, Malawi.
Zia Yasaman Y Tang Jennifer H JH Chinula Lameck L Tegha Gerald G Stanczyk Frank Z FZ Kourtis Athena P AP
Contraception 20190730 5
<h4>Objective</h4>To compare medroxyprogesterone acetate (MPA) concentrations between HIV-positive women on antiretroviral therapy (ART) and HIV-negative women initiating depot medroxyprogesterone (DMPA) injectable.<h4>Study design</h4>Secondary analysis of 28 HIV-positive women on non-nucleoside reverse transcriptase inhibitor-containing ART regimens and 10 HIV-negative women randomized to initiate DMPA in a clinical trial of progestin contraception in Malawi.<h4>Results</h4>MPA concentrations ...[more]
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Project description:To evaluate contraceptive adherence to the copper intrauterine device (Cu-IUD) and the injectable depot medroxyprogesterone acetate (DMPA) among women with HIV in Lilongwe, Malawi.We randomized 200 HIV-infected women on highly active antiretroviral therapy (HAART) to either the Cu-IUD or DMPA and followed these women prospectively, evaluating adherence and factors associated with nonadherence.There was no difference in contraceptive adherence: 68% of Cu-IUD and 65% of DMPA users were adherent at 48 weeks. Receiving first-choice contraceptive was not associated with adherence. Women commonly cited partner's disapproval as an indication for discontinuation. Women who experienced heavy menstruation and first-time contraceptive users were more likely to be nonadherent. Among ongoing users at study conclusion, 95% were happy with their method, and 98% would recommend their method to a friend.Contraceptive adherence between the Cu-IUD and DMPA was similar at 1 year. With similar adherence and similar high rates of satisfaction among users of both methods at 1 year, the Cu-IUD offers a hormone-free alternative to DMPA.Adherence to the Cu-IUD and DMPA is similar at 1 year among HIV-infected women on HAART in a randomized controlled trial. Despite high method satisfaction, partner disapproval and heavy bleeding contribute to reduced adherence. Receiving a method that differs from participant's first-choice method did not influence adherence.
| S-EPMC4108248 | biostudies-literature
Project description:ObjectivesTo characterize the relationship between serum medroxyprogesterone acetate (MPA) concentrations and ovulation suppression, and to estimate the risk of ovulation for investigational subcutaneous regimens of Depo-Provera CI (Depo-Provera) and Depo-subQ Provera 104 (Depo-subQ).Study designWe performed a secondary analysis of 2 studies that assessed the pharmacokinetics and pharmacodynamics of MPA when Depo-Provera is administered subcutaneously rather than by the labeled intramuscular route. Each woman received a single 45 mg to 300 mg subcutaneous injection of Depo-Provera, a single 104 mg subcutaneous injection of Depo-subQ, or 2 injections of Depo-subQ at 3-month intervals. We used an elevation of serum progesterone ≥4.7 ng/mL as a surrogate for ovulation and non-parametric statistical methods to assess pharmacokinetic and pharmacodynamic relationships.ResultsThis analysis included 101 women with body mass index (BMI) 18 to 34 kg/m2. Return of ovulation occurred at a median MPA concentration of 0.07 ng/mL (95% CI: 0.06-0.08) and the 90th percentile was 0.10 ng/mL (95% CI: 0.09-0.14). Neither age, race, nor BMI significantly influenced this relationship. The estimated probabilities of ovulation within 4 months of a 104 mg subcutaneous injection and within 7 months of a 150 mg subcutaneous injection (6 plus a 1-month grace) were each below 2.2%.ConclusionsThe typical MPA concentration associated with loss of ovulation suppression is substantially less than the commonly cited threshold of 0.2 ng/mL. Based on our results, MPA levels would rarely be low enough to permit ovulation if the Depo-subQ reinjection interval were extended to four months or if 150 mg Depo-Provera were injected subcutaneously every 6 months.ImplicationsExtending the three-month Depo-subQ reinjection interval by one month would result in a 25% reduction in yearly MPA exposure, with little risk of pregnancy. Off-label subcutaneous administration of 150 mg Depo-Provera every 6 months would be a highly effective repurposing of an excellent product, with a similar reduction in cumulative exposure.
| S-EPMC8907671 | biostudies-literature
Project description:Depot medroxyprogesterone acetate is an injectable hormonal contraceptive, widely used by women of childbearing potential living with HIV and/or tuberculosis. As medroxyprogesterone acetate is a cytochrome P450 (CYP3A4) substrate, drug-drug interactions (DDIs) with antiretroviral or antituberculosis treatment may lead to subtherapeutic medroxyprogesterone acetate concentrations (< 0.1 ng/mL), resulting in contraception failure, when depot medroxyprogesterone is dosed at 12-week intervals. A pooled population pharmacokinetic analysis with 744 plasma medroxyprogesterone acetate concentrations from 138 women treated with depot medroxyprogesterone and antiretroviral/antituberculosis treatment across three clinical trials was performed. Monte Carlo simulations were performed to predict the percentage of participants with subtherapeutic medroxyprogesterone acetate concentrations and to derive alternative dosing strategies. Medroxyprogesterone acetate clearance increased by 24.7% with efavirenz coadministration. Efavirenz plus antituberculosis treatment (rifampicin + isoniazid) increased clearance by 52.4%. Conversely, lopinavir/ritonavir and nelfinavir decreased clearance (28.7% and 15.8%, respectively), but lopinavir/ritonavir also accelerated medroxyprogesterone acetate's appearance into the systemic circulation, thus shortening the terminal half-life. A higher risk of subtherapeutic medroxyprogesterone acetate concentrations at Week 12 was predicted on a typical 60-kg woman on efavirenz (4.99%) and efavirenz with antituberculosis treatment (6.08%) when compared with medroxyprogesterone acetate alone (2.91%). This risk increased in women with higher body weight. Simulations show that re-dosing every 8 to 10 weeks circumvents the risk of subtherapeutic medroxyprogesterone acetate exposure associated with these DDIs. Dosing depot medroxyprogesterone every 8 to 10 weeks should eliminate the risk of subtherapeutic medroxyprogesterone acetate exposure caused by coadministered efavirenz and/or antituberculosis treatment, thus reducing the risk of contraceptive failure.
| S-EPMC8449800 | biostudies-literature
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.
| S-EPMC10688740 | biostudies-literature
Project description:Depot medroxyprogesterone acetate administered subcutaneously (DMPA-SC) is an all-in-one injectable contraceptive administered every 3 months, either by a trained health care provider or community health worker or by training a client to self-inject. Using a prospective cohort of family planning (FP) clients in Ghana, this study explores patterns of DMPA-SC use and mode of injection administration over a 6-month period. This study also examines the predictors of self-injection adoption 6 months after initiating DMPA-SC. Our analysis focuses on 378 women who were using DMPA-SC at the 6-month interview. Adjusted odds ratios accounting for clustering show that clients who were new FP users, never married, or attended high school/attained higher education were significantly more likely to self-inject by the third injection. Results of this study suggest that in Ghana, adding DMPA-SC to the method mix may improve access to FP, especially among new users. Results of this study may inform FP projects and programs aiming to improve access to contraceptive methods and increase contraceptive prevalence by introducing or scaling up DMPA-SC self-injection. The findings also provide a sociodemographic profile of FP clients most likely to adopt DMPA-SC self-injection over time, which could serve as an evidence base for social marketing strategies.
| S-EPMC8885352 | biostudies-literature
Project description:ObjectiveTo assess the supply- and demand-side factors influencing continued use of the injectable contraceptive subcutaneous depot medroxyprogesterone acetate (DMPA-SC).MethodsWe conducted a 12-month randomized controlled trial in Malawi to measure DMPA-SC continuation rates. A total of 731 women presenting to clinic-based providers (CBPs) at 6 Ministry of Health clinics or to community health workers (CHWs) in rural communities were randomized to receive DMPA-SC administered by a provider or be trained to self-inject DMPA-SC. Data collectors contacted women after the reinjection window at 3, 6, and 9 months to collect data on discontinuation and women's experiences. Twelve months after enrollment or at early discontinuation, women had their final interview, including pregnancy testing. We compared continuation, pregnancy, and safety by whether DMPA-SC or self-injection training was provided by CHWs versus CBPs. We also conducted an exploratory analysis assessing the association between women's sociodemographic factors and the risk for discontinuation using stratified Cox proportional hazards models.FindingsThe type of provider did not seem to influence continuation, pregnancy, or safety. As reported previously, women in the self-injection group were significantly less likely to discontinue the method compared with women in the provider-administered group (hazard ratio, 0.43; P<.001). The risk for discontinuation was also different among health facility catchment sites (P<.001). No other assessed sociodemographic factors were found to significantly influence the risk for discontinuation.ConclusionsPublic-sector CHWs can safely and effectively provide DMPA-SC and train women to self-inject DMPA-SC in low-resource settings. DMPA-SC continuation did not seem to be influenced by the type of provider, whether CBP or CHW, or women's sociodemographic characteristics.
| S-EPMC6538126 | biostudies-literature
Project description:Prevention of HIV infection and unintended pregnancies are public health priorities. In sub-Saharan Africa, where HIV prevalence is highest, depot medroxyprogesterone acetate (DMPA) is widely used as contraception. Therefore, understanding potential interactions between DMPA and antiretrovirals is critical. Here, we use a macaque model to investigate the effect of DMPA on the pharmacology of the antiretroviral tenofovir alafenamide (TAF). Female rhesus macaques received 30 mg of DMPA (n = 9) or were untreated (n = 9). Macaques received a human equivalent dose of TAF (1.5 mg/kg) orally by gavage. Tenofovir (TFV) and TFV-diphosphate (TFV-DP) were measured in blood, secretions, and tissues over 72 h. The median area under the curve (AUC0-72h) values for TFV-DP in peripheral blood mononuclear cells were similar in DMPA-treated (6991 fmol*h/106 cells) and untreated controls (5256 fmol*h/106 cells) (P = 0.174). Rectal tissue TFV-DP concentrations from DMPA+ animals [median: 20.23 fmol/mg of tissue (range: 4.94-107.95)] were higher than the DMPA- group [median: below the limit of quantification (BLOQ-11.92)], (P = 0.019). TFV-DP was not detectable in vaginal tissue from either group. A high-dose DMPA treatment in macaques was associated with increased rectal TFV-DP levels, indicating a potential tissue-specific drug-drug interaction. The lack of detectable TFV-DP in the vaginal tissue warrants further investigation of PrEP efficacy with single-agent TAF products. DMPA did not affect systemic TAF metabolism, with similar PBMC TFV-DP in both groups, suggesting that DMPA use should not alter the antiviral activity of TAF.
| S-EPMC8480307 | biostudies-literature
Project description:ObjectiveInvestigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.MethodsWe conducted a cohort study in the Detroit, Michigan, area that involved four clinic visits at 20-month intervals over 5 years (2010-2018) and used a standardized ultrasonography protocol to prospectively measure leiomyomas 0.5 cm or more in diameter. Participants were 1,693 self-identified Black women aged 23-35 years with no prior leiomyoma diagnosis and no hysterectomy. For this substudy, years since last use of DMPA was ascertained from questionnaire data at every visit. Leiomyoma incidence was defined as the first visit with an observed leiomyoma among women who were leiomyoma-free at enrollment. Depot medroxyprogesterone acetate associations were examined with Cox models. Leiomyoma growth was calculated as the change in log-volume for leiomyomas matched at successive visits and was modeled using linear mixed models accounting for clustered data. Leiomyoma loss, defined as a reduction in leiomyoma number in successive visits, was modeled using Poisson regression. All models used time-varying exposure and covariates.ResultsOf participants with at least one follow-up visit (N=1,610), 42.9% had ever used DMPA. Participants exposed to DMPA within the previous 2 years experienced reduced leiomyoma development during the subsequent observation interval compared with never users, including lower leiomyoma incidence (5.2% vs 10.7%), adjusted hazard ratio 0.6 (95% CI 0.4-1.0), 42.0% lower leiomyoma growth (95% CI -51.4 to -30.7) and 60% greater leiomyoma loss (adjusted risk ratio 1.6, 95% CI 1.1-2.2). Excess leiomyoma loss was also seen for those who used DMPA 2-4 years before the visit compared with never users, 2.1-fold increase (95% CI 1.4-3.1).ConclusionRecent use of DMPA was associated with reduced leiomyoma development and increased leiomyoma loss. Such changes in early leiomyoma development in young women could delay symptom onset and reduce the need for invasive treatment.
| S-EPMC9015023 | biostudies-literature
Project description:ObjectiveTo examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle development.Study designWe assigned enrolled participants to one of three preassigned dominant follicle size groups: 12-14 mm, 15-17 mm and ≥ 18 mm. We followed dominant follicles via serial transvaginal ultrasound (TVUS) until the follicles reached their assigned size, at which time we administered DMPA. For 5 consecutive days thereafter, we followed the follicles via TVUS to observe follicle rupture and obtained serum luteinizing hormone (LH), estradiol, and progesterone concentrations. In the following 2 weeks, we collected serum progesterone concentrations twice weekly to detect possible ovulatory delay or dysfunction. We also collected serum medroxyprogesterone acetate (MPA) concentrations at 1 and 24 h after DMPA administration to examine against ovulatory outcomes.ResultsTwenty-six of 29 enrolled women completed the study. DMPA suppressed ovulation in 17/26 (65%) and caused ovulatory dysfunction in 1/26 (4%) participants. Larger follicles were more likely to rupture despite DMPA (12-14 mm: 0/10 (0%); 15-17 mm: 3/10 (30%); ≥ 18 mm: 6/6 (100%); p < .01). Pre-DMPA LH concentrations ranged from 13.8 to 93.7 IU/L (mean 49.0 IU/L) in cases of follicle rupture. We observed no cases of follicle rupture when DMPA was administered through cycle day 12. All 24-h MPA concentrations exceeded those needed for ovulation suppression.ConclusionDMPA suppressed and additionally disrupted ovulation in 65% and 4% of observed cycles, respectively. DMPA may provide effective emergency contraception as well as ongoing contraception if administered prior to an expected ovulation and specifically before the LH surge.ImplicationsDMPA may be an alternative form of emergency contraception that can also self-bridge to ongoing contraception. As ovulation was not observed among any follicles when DMPA was given through cycle day 12, women who initiate DMPA up through cycle day 12 may not require backup contraception.
| S-EPMC7749364 | biostudies-literature
Project description:ObjectiveTo describe the implementation and results of a proactive patient outreach project to offer self-administered, depot medroxyprogesterone (DMPA) subcutaneous (SC) to interested patients at a California safety-net clinic following expanded state Medicaid coverage.Study designWe contacted non-pregnant patients at an urban, safety-net hospital-based primary care clinic who had been prescribed DMPA intramuscular (IM) in the past year to gauge interest in self-administered DMPA-SC. Interested patients received a prescription for DMPA-SC and a telehealth appointment with a clinic provider to learn self-injection. We recorded patient interest in DMPA-SC, completed appointments, and completed first injections. We conducted initial outreach in May, 2020 and recorded appointment attendance and completed injections through August, 2020.ResultsOf 90 eligible patients (age 17-54), we successfully contacted and discussed DMPA-SC with 70 (78%). Twenty-six (37%) patients expressed interest in DMPA-SC and scheduled telehealth appointments to learn to self-administer the medication. Fifteen (58%) of those interested (21% of the total) successfully self-injected DMPA-SC. Of the 44 (63%) patients not interested in DMPA-SC, the three most common reasons were fear of self-injection (n = 23 [52%]), wanting to stop DMPA (n = 11 [25%]), and satisfaction with DMPA-IM (n = 6 [14%]).ConclusionThere is interest in and successful initiation of self-administered DMPA-SC among patients at an urban safety net hospital-based primary care clinic who have used DMPA-IM in the last year.ImplicationsOur data provide evidence for the interest and successful first injection rate after offering self-administered DMPA-SC to patients on DMPA-IM. Expanding coverage of self-administered DMPA-SC could increase patient-centeredness and accessibility of contraception as well as reduce patient anxiety around COVID-19 transmission without losing contraceptive access.
| S-EPMC7486600 | biostudies-literature