Factors Affecting Continued Use of Subcutaneous Depot Medroxyprogesterone Acetate (DMPA-SC): A Secondary Analysis of a 1-Year Randomized Trial in Malawi.

OBJECTIVE: To assess the supply- and demand-side factors influencing continued use of the injectable contraceptive subcutaneous depot medroxyprogesterone acetate (DMPA-SC). METHODS: We 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. FINDINGS: The 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. CONCLUSIONS: Public-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.

Women's satisfaction, use, storage and disposal of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) during a randomized trial.

OBJECTIVE: To describe women's experiences with subcutaneous depot medroxyprogesterone acetate (DMPA-SC) to inform scale-up of self-administered DMPA-SC. STUDY DESIGN: We conducted a 12-month randomized controlled trial in Malawi to measure DMPA-SC continuation rates. A total of 731 women presenting at six 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 satisfaction and use; self-injectors were also queried about storage and disposal of DMPA-SC. We compared frequencies of injection experiences and satisfaction by study group and over time. RESULTS: Ninety-two percent of women who self-injected felt it was easy to do the first time. Women in the self-administered group primarily gave themselves the injection versus having someone else inject them; stored DMPA-SC mostly in bags, often in ways to keep the product away from others; and properly disposed of DMPA-SC in pit latrines. Women in both groups used printed calendars to remember when to get/be given their next injection. Both groups reported high satisfaction with DMPA-SC. CONCLUSIONS: Women in low-resource settings can be successfully trained by public sector CHWs and clinic-based providers to self-inject and to appropriately store and dispose of DMPA-SC. DMPA-SC and self-injection are acceptable and feasible in a low-resource setting. IMPLICATIONS: Self-administered and provider-administrated DMPA-SC should be scaled up, and the lessons learned during our trial should be applied to future scale-up efforts.

Effect of self-administration versus provider-administered injection of subcutaneous depot medroxyprogesterone acetate on continuation rates in Malawi: a randomised controlled trial.

BACKGROUND: Injectable contraceptives are popular in sub-Saharan Africa but have high discontinuation rates due partly to the need for provider-administered re-injection. We compared continuation rates of women who self-injected subcutaneous depot medroxyprogesterone acetate (DMPA-SC) and women who received DMPA-SC from a health-care provider, including community health workers (CHWs). METHODS: We did an open-label randomised controlled trial based at six Ministry of Health clinics in rural Mangochi District, Malawi. Health-care providers recruited adult women who presented at the six clinics or to CHWs in rural communities in the clinic catchment areas. Participants received DMPA-SC and were randomised (1:1) to receive provider-administered injections or training in how to self-inject DMPA-SC. Randomisation was done via a computer-generated block randomisation schedule with block sizes of four, six, and eight and stratified by study site, generated by an independent statistician. Self-injectors administered the first injection under observation and were sent home with three doses, written instructions, and a calendar. The provider-administered group received a DMPA-SC injection and a calendar, and were asked to return for subsequent injections. Data collectors contacted participants after the 14-week re-injection window at 3, 6, and 9 months to collect continuation data. At 12 months after enrolment or early discontinuation, women had their final interview, which included pregnancy testing. The primary outcome was discontinuation of DMPA-SC, as assessed in the intention-to-treat population. We used Kaplan-Meier methods to estimate the probabilities of continuation and a log-rank test to compare groups. Safety was assessed in the as-treated population, which consisted only of participants who successfully received at least one DMPA-SC injection after randomisation. This trial is registered with ClinicalTrials.gov, number NCT02293694. FINDINGS: This study lasted from Sept 17, 2015, to Feb 21, 2017. 731 women underwent randomisation, with 364 assigned to the self-administered group and 367 to the provider-administered group. One woman in the self-injection group withdrew at month 0. Treatment was discontinued by 99 women in the self-administered group and 199 women in the provider-administered group. The 12 month continuation rate was 73% in the self-injection group and 45% in the provider-administered group, giving an incidence rate ratio of 0·40 (95% CI 0·31-0·51; p<0·0001). Adverse events deemed to potentially be treatment-related were reported by ten women (20 events) in the self-administered group and 17 women (28 events) in the provider-administered group. Five serious adverse events were reported during the trial by four women; two events related to DMPA-SC (menorrhagia and anaemia requiring hospital admission) were reported by the same woman in the provider-administered group and resolved without sequelae. The other serious adverse events, including one death, were deemed to be unrelated to DMPA-SC. INTERPRETATION: Women who self-injected DMPA-SC had significantly higher rates of continuation than those receiving provider-injected DMPA-SC. Community-based provision of injectable contraception for self-injection in low-resource settings seems to be safe and feasible. Self-administration of DMPA-SC should be made widely available. FUNDING: United States Agency for International Development and Children's Investment Fund Foundation.

Sexual behavior before and after pregnancy detection in four microbicide trials.

Vaginal microbicide gel trials for HIV prevention may require withdrawal of study product when a woman becomes pregnant. We assessed the potential impact of withdrawals in four trials by comparing self-reported sexual behavior pre- and post-pregnancy detection: (1) behavior in the month prior to positive pregnancy test versus behavior reported at the subsequent monthly visit; (2) behavior changes according to pregnancy status at the subsequent visit (continuing pregnancy versus not); (3) average sexual behaviors reported for all months prior to pregnancy detection versus all months after pregnancy was no longer detected; and (4) behavior changes among participants never testing positive for pregnancy. Pregnancy detection was associated with immediate reductions in self-reported numbers of partners and sex acts. The proportion of acts in which study gel was used following a negative pregnancy test did not return to pre-pregnancy levels. Pregnancies complicate the conduct and interpretation of vaginal microbicide trials when product must be withdrawn.

SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria.

BACKGROUND: The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk. METHODOLOGY/PRINCIPAL FINDINGS: This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1 ratio 1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use. CONCLUSIONS/SIGNIFICANCE: SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY.

Randomized assignment to copper IUD or depot-medroxyprogesterone acetate: feasibility of enrollment, continuation and disease ascertainment.

OBJECTIVES: We conducted a feasibility study to enroll and follow family planning acceptors who were randomly assigned to use an intrauterine device (IUD) or injectable depot-medroxyprogesterone acetate (DMPA). METHODS: Centers in Brazil, Guatemala, Egypt and Vietnam aimed to enroll 100 participants per site. Enrolled women were randomly assigned to have inserted a TCu 380A IUD, or to receive injections of 150 mg of DMPA every 3 months, and scheduled for up to 12 months of follow-up. We tested for cervical infection at first and final visits, and examined for signs of pelvic inflammatory disease (PID) at each visit. RESULTS: The sites screened 555 women and enrolled 368. Two women (0.5%) had three discomfort signs of PID during follow-up. The prevalence of gonorrhea at each woman's final follow-up visit was 0.5%, and the prevalence of chlamydia at final visit was 5.4%. Sixty-eight percent of women either completed 12 months of observation with their assigned method or were still using their method at the end of the study. CONCLUSION: A larger, definitive clinical trial appears feasible. The majority of women we approached agreed to participate; nearly 400 women were enrolled; two thirds continued to use their assigned method until study closeout; and the STI risk was moderate.