Depression Among Pregnant and Breastfeeding Persons Participating in Two Randomized Trials of the Dapivirine Vaginal Ring and Oral Pre-Exposure Prophylaxis (PrEP) in Malawi, South Africa, Uganda, and Zimbabwe.

Depression is associated with lower adherence to oral pre-exposure prophylaxis (PrEP) to prevent HIV, but data are not currently available on how depression may affect use of other HIV prevention methods including the dapivirine vaginal ring (DVR). We conducted a mixed methods study using data from the Microbicide Trials Network (MTN) 042/DELIVER (n = 558) and MTN-043/B-PROTECTED (n = 197) studies to describe the prevalence of depressive symptoms and explore how depressive symptoms may have influenced attitudes about use of the monthly DVR and once-daily oral PrEP tablet among pregnant and breastfeeding persons, respectively, in Malawi, South Africa, Uganda, and Zimbabwe. Eleven participants had high Edinburgh Postnatal Depression scores ≥ 10 in MTN-042/DELIVER (2%) and four participants (2%) in MTN-043/B-PROTECTED. In interviews with 9 participants who had high scores (6 DVR, 3 oral PrEP), those with depressive symptoms described overlapping stressors which were magnified by job loss and economic instability during the COVID-19 pandemic, and by experiences of pregnancy/postpartum. These participants experienced a lack of support from partners or family members, and conflict with partners related to trust, and infidelity. While we did not find evidence of a change in product adherence, there was a strong sense of commitment and motivation to use the study products for protection from HIV for participants themselves and their baby. Although lack of social support is usually an obstacle to adherence, in this study, the participants' lives and relationships seemed to have reinforced the need for HIV prevention and motivated women to protect themselves and their babies from HIV.

Acceptability and Use of the Dapivirine Vaginal Ring and Daily Oral Pre-exposure Prophylaxis (PrEP) During Breastfeeding in South Africa, Malawi, Zimbabwe, and Uganda.

This study examines qualitative acceptability of the dapivirine vaginal ring (DVR) and oral daily pre-exposure prophylaxis (PrEP) among breastfeeding persons participating in Microbicide Trials Network 043/B-PROTECTED, a phase 3B safety and drug detectability study of DVR and oral PrEP in breastfeeding. A subsample of 52 participants were purposively sampled to participate in an in-depth interview (IDI). Breastfeeding participants found both study products to be acceptable, and easy to use. A common motivation for product use was to protect the baby from HIV, although participants' understanding of how the study drug would work to protect their babies was often unclear. While most participants did not report experiencing side effects, fears about side effects were common as both initial worries about how the study products would affect their health and the health of their baby, and increased anxiety that health issues experienced by them, or their baby were from the products.

A clustered randomized control trial to assess feasibility, acceptability, and impact of implementing the birth companion intervention package in Ethiopia, Kenya, and Nigeria: study protocol.

BACKGROUND: A birth companion is a simple and low-cost intervention that can improve both maternal and newborn health outcomes. The evidence that birth companionship improves labor outcomes and experiences of care has been available for many years. Global and national policies exist in support of birth companions. Many countries including Ethiopia, Kenya, and Nigeria have not yet incorporated birth companions into routine practice in health facilities. This paper presents the protocol for a trial that aims to assess if a package of interventions that addresses known barriers can increase the coverage of birth companions. METHODS: This two parallel arm cluster randomized controlled trial will evaluate the impact of a targeted intervention package on scale-up of birth companionship at public sector health facilities in Ethiopia (five study sites encompassing 12 facilities), Kenya (two sites encompassing 12 facilities in Murang'a and 12 facilities in Machakos counties), and Nigeria (two sites encompassing 12 facilities in Kano and 12 facilities in Nasarawa states). Baseline and endline assessments at each site will include 744 women who have recently given birth in the quantitative component. We will interview a maximum of 16 birth companions, 48 health care providers, and eight unit managers quarterly for the qualitative component in each country. DISCUSSION: Ample evidence supports the contribution of birth companions to positive health outcomes for mothers and newborns. However, limited data are available on effective strategies to improve birth companion coverage and inform scale-up efforts. This trial tests a birth companion intervention package in diverse clinical settings and cultures to identify possible barriers and considerations to increasing uptake of birth companions. Findings from this study may provide valuable evidence for scaling up birth companionship in similar settings. TRIAL REGISTRATION: Trial is registered with ClinicalTrials.gov with identifier: NCT05565196, first posted 04/10/ 2022.

Impact of Dapivirine and Placebo Vaginal Rings on the Microbiota of Adolescent, Lactating, and Postmenopausal Females.

BACKGROUND: A 25-mg dapivirine vaginal ring has been demonstrated to reduce risk of human immunodeficiency virus (HIV) acquisition in nonpregnant adult women. In this secondary analysis of studies conducted in US adolescent, lactating, and postmenopausal females, vaginal microbiota was assessed prior to and after ring use, and between dapivirine and placebo ring users. METHODS: Vaginal fluid swabs were collected before and after product use for the evaluation of microbiota using Nugent criteria, quantitative culture, and quantitative polymerase chain reaction. RESULTS: Vaginal ring use did not impact bacterial vaginosis prevalence among the 3 populations and was associated with minimal shifts in microbiota. Adolescents in both arms demonstrated an increased prevalence of Lactobacillus crispatus and a decrease in quantity of Megasphaera lornae. Postmenopausal active and placebo ring users demonstrated an increased prevalence of lactobacilli and non-albicans yeast, while dapivirine ring users demonstrated an increased prevalence of Candida albicans and increased quantity of group B Streptococcus and non-albicans yeasts. Prevotella species were increased in lactating women, whereas Prevotella timonensis increased in prevalence and concentration among adolescent and postmenopausal females and Prevotella bivia increased in prevalence among adolescent dapivirine ring users. CONCLUSIONS: Dapivirine vaginal ring use was associated with minimal changes in the vaginal microbiota that are likely not clinically significant.

Effect of group versus individual antenatal care on uptake of intermittent prophylactic treatment of malaria in pregnancy and related malaria outcomes in Nigeria and Kenya: analysis of data from a pragmatic cluster randomized trial.

BACKGROUND: Every year, malaria in pregnancy contributes to approximately 20% of stillbirths in sub-Saharan Africa and 10,000 maternal deaths globally. Most eligible pregnant women do not receive the minimum three recommended doses of intermittent preventive treatment with Sulfadoxine-pyrimethamine (IPTp-SP). The objective of this analysis was to determine whether women randomized to group antenatal care (G-ANC) versus standard antenatal care (ANC) differed in IPTp uptake and insecticide-treated nets (ITN) use. METHODS: Prospective data were analysed from the G-ANC study, a pragmatic, cluster randomized, controlled trial that investigated the impact of G-ANC on various maternal newborn health-related outcomes. Data on IPTp were collected via record abstraction and difference between study arms in mean number of doses was calculated by t test for each country. Data on ITN use were collected via postpartum interview, and difference between arms calculated using two-sample test for proportions. RESULTS: Data from 1075 women and 419 women from Nigeria and Kenya, respectively, were analysed: 535 (49.8%) received G-ANC and 540 (50.2%) received individual ANC in Nigeria; 211 (50.4%) received G-ANC and 208 (49.6%) received individual ANC in Kenya. Mean number of IPTp doses received was higher for intervention versus control arm in Nigeria (3.45 versus 2.14, p < 0.001) and Kenya (3.81 versus 2.72, p < 0.001). Reported use of ITN the previous night was similarly high in both arms for mothers in Nigeria and Kenya (over 92%). Reported ITN use for infants was higher in the intervention versus control arm in Nigeria (82.7% versus 75.8%, p = 0.020). CONCLUSIONS: G-ANC may support better IPTp-SP uptake, possibly related to better ANC retention. However, further research is needed to understand impact on ITN use. Trial registration Pan African Clinical Trials Registry, May 2, 2017 (PACTR201706002254227).

Pharmacokinetics of Dapivirine Transfer into Blood Plasma, Breast Milk, and Cervicovaginal Fluid of Lactating Women Using the Dapivirine Vaginal Ring.

Breastfeeding (BF) women are an important population for biomedical HIV prevention strategies, but they are rarely included in trials. The 25-mg dapivirine vaginal ring (VR) reduced women's risk of sexually transmitted HIV infection in two phase 3 trials conducted in Africa. We conducted a phase 1, open-label study (MTN-029/IPM 039) of dapivirine VR use among lactating women in Pittsburgh, PA, and Birmingham, AL, USA. MTN-029/IPM 039 enrolled 16 healthy adult women who had already weaned their infants but were still able to express breast milk. Women were instructed to use the VR continuously for 14 days and provided milk, plasma, and cervicovaginal fluid (CVF) samples for pharmacological analysis. No infants were exposed to the drug, but infant dosage was estimated according to FDA guidance. Adverse events (AEs) were collected at all contacts. The study was completed with 100% participant retention. Median dapivirine concentrations were 676 pg/ml in breast milk, 327 pg/ml in plasma (milk/plasma ratio ∼2.0), and 36.25 ng/mg in CVF. Six participants experienced 10 total AEs, none of which required VR discontinuation. The estimated mean daily infant dosage was 74.3 ng/kg/day. In this first study of dapivirine exposure during lactation, dapivirine VR use was associated with lower concentrations of detectable dapivirine in milk and plasma than in CVF samples and a favorable safety profile. Estimated daily levels of infant dapivirine exposure were also low. Additional studies are needed to evaluate longer periods of dapivirine VR use among BF mother-infant pairs living in regions with higher incidence of sexually transmitted HIV infection. (This study has been registered at ClinicalTrials.gov under registration no. NCT02808949.).

Tenofovir-based preexposure prophylaxis for HIV infection among African women.

BACKGROUND: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS: Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).

Acceptability of and Adherence to an Antiretroviral-Based Vaginal Microbicide among Pregnant Women in the United States.

The MTN-008 trial was the first multi-dose study conducted to evaluate the safety of a microbicide gel (2:1 randomized to tenofovir 1% or hydroxycellulose (HEC) placebo gel) during pregnancy. The study aim was to evaluate safety, tolerability and pharmacokinetics of the study products. Procedures included daily gel administration, with Day 0 and Day 6 in clinic, and Days 1-5 at home. Because pregnancy may pose unique challenges to consistent gel use and acceptability, evaluation of adherence and acceptability was a secondary objective of the trial. The study enrolled healthy, HIV-negative, pregnant women aged 18-40 in Pittsburgh, PA and Birmingham, AL, USA in 2 consecutive groups: cohort 1 was 37-39 weeks gestation, cohort 2 was 34-36 weeks. Ninety-one women completed the study (45 and 46 in each cohort, respectively) and were evaluable per protocol. Adherence was evaluated using self-reports: participants completed a web-based computer-assisted self-interview (CASI) at Days 0 and 6 about gel attitudes and behaviors. At Day 6 trained research staff conducted a short interviewer-administered questionnaire with both structured and open-ended questions. Frequencies of quantitative data were tabulated in SAS and descriptive statistics are presented; open-ended textual data were summarized by a behavioral scientist experienced in qualitative analysis. Participants reported generally neutral perceptions of gel characteristics. A small number of women (7-8%) reported pain (6/90), other physical discomfort (7/90), or mental discomfort (7/90) associated with the process of applicator insertion. About 5% reported the same for the gel itself. Two-thirds (61/90) thought the gel was runny, many complained of bothersome gel leakage and several cited this reason for not inserting a full dose. The majority were not worried the gel would cause problems for their pregnancy or babies. Ninety-seven percent (83/86) said they would use the gel in the future if they were pregnant, and 90% (81/90) when nonpregnant. Self-reported adherence was high with 88% (79/90) reporting daily gel use on both the computerized and interviewer-administered questionnaires. The majority (67/90) reported no difficulty with daily use. However, drug was undetectable (<0.31 ng/mL) among 45% (27/60; 95% CI 32-58%) of the women on active product prior to observed dosing at Day 6. The most common reason for reported nonuse (N = 6) was forgetting. Study gel was generally acceptable, but many complained of a runny consistency (61/90) and leakage (83/90). No frequent or strong concerns about the effects of the study gel on the pregnancy/fetus were reported. Self-reported adherence to study gel self-administered at home for 5 days was high, however plasma drug levels suggest actual use may have been considerably lower. Findings from this study can provide insights relevant to use of other antiretroviral-based, vaginally-inserted HIV prevention methods during pregnancy.

Detectable Tenofovir Levels in Breast-Feeding Infants of Mothers Exposed to Topical Tenofovir.

Lactation studies are necessary evaluations of medications for reproductive-age women. We evaluated pharmacokinetics (PK), pharmacodynamics, safety, and adherence profiles associated with 7 days of 1% tenofovir (TFV) vaginal gel use during lactation. Tenofovir levels (maternal/infant serum, milk) and anti-HIV activity (milk), adverse events (AEs), and adherence were measured for 17 HIV-1-seronegative breast-feeding mother-infant pairs. Tenofovir use was well-tolerated and detected at low levels in maternal serum, milk, and infant serum but demonstrated no anti-HIV activity in milk.

Pharmacokinetics and placental transfer of single-dose tenofovir 1% vaginal gel in term pregnancy.

UNLABELLED: Tenofovir (TFV) 1% vaginal gel has been found to decrease sexual transmission of human immunodeficiency virus. To initiate investigations during pregnancy, 16 healthy pregnant women scheduled for cesarean delivery received a single application of TFV gel preoperatively. Maternal serum drug concentrations were determined and fetal cord blood, amniotic fluid, placental tissue, and endometrial tissue specimens were collected. The median maternal peak concentration and cord blood TFV concentrations were 4.3 and 1.9 ng/mL, respectively (∼100- and 40-fold lower than after TFV oral dosing, respectively). No adverse events were related to the use of TFV gel. These findings support ongoing and future investigations of TFV gel in pregnancy. CLINICAL TRIAL REGISTRATION: NCT00572273. http://www.clinicaltrials.gov/ct2/show/NCT00540605?term=mtn-002&rank=1.

A socio-ecological exploration to identify factors influencing the COVID-19 vaccine decision-making process among pregnant and lactating women: Findings from Kenya.

The vaccine decision-making process of pregnant and lactating women is complex. Regarding COVID-19, pregnant women are at increased risk for severe disease and poor health outcomes. While pregnant and lactating women were excluded from COVID-19 vaccine trials, available evidence suggests that COVID-19 vaccines are safe and protective during pregnancy. In this study, we used a socio-ecological approach to explore factors influencing the decision-making process for COVID-19 vaccines in pregnant and lactating women in Kenya, for the purpose of informing demand generation strategies. As pregnant and lactating women are influenced by many factors, we conducted 84 in-depth interviews with a variety of stakeholders, including 31 pregnant or lactating women, 20 healthcare workers such as nurses, midwives, doctors, and frontline workers, 25 male family members of pregnant or lactating women, and 8 gatekeepers such as community leaders and faith-based leaders. These individuals were recruited from six communities in Kenya: three urban, and three rural. We applied a grounded theory approach to identify emerging themes and organized emerging themes using the SAGE Vaccine Hesitancy model, which includes three categories of determinants of vaccine acceptance, including contextual influences, individual and group influences, and vaccine and vaccination specific issues. Myths, interpersonal norms, and religion emerged as themes related to contextual influences. Safety, risk perception, and the role of the healthcare worker emerged as themes related to individual and group influences. For vaccine and vaccination specific issues, emerging themes included availability, accessibility, and eligibility. While maternal immunization can substantially reduce the effect of infectious diseases in mothers and infants, vaccine acceptance is critical. However, vaccines do not save lives; vaccination does. We hope the results of this study can be used to tailor communication efforts to increase vaccine demand among pregnant and lactating women.

Where are the pregnant and breastfeeding women in new pre-exposure prophylaxis trials? The imperative to overcome the evidence gap.

Pregnant and breastfeeding populations are at substantial risk of acquiring HIV in some settings, yet are underrepresented in clinical trials of new pre-exposure prophylaxis (PrEP) agents. Several PrEP formulations are in development (eg, vaginal rings, long-acting injectables, and other modalities). Pregnant and breastfeeding populations are typically excluded from initial clinical trials. We identified 14 PrEP trials of novel agents in non-pregnant or non-breastfeeding populations, and six phase 1-3 trials and open label extensions among pregnant and breastfeeding populations, that are currently ongoing or complete. A framework shift is needed to consider the ethical costs of excluding pregnant and breastfeeding populations at risk for HIV in PrEP clinical trials and promote inclusion to maximise the benefits from PrEP tools in the pipeline. Research on new PrEP agents should include pregnant and breastfeeding populations to avoid delays in reaching those who could benefit from PrEP after efficacy is established.

Fostering community understanding of sufficient benefit and early stopping for a phase 2B HIV prevention clinical trial in Africa.

BACKGROUND: Most trials of interventions are designed to address the traditional null hypothesis of no benefit. VOICE, a phase 2B HIV prevention trial funded by NIH and conducted in Africa, is designed to assess if the intervention will prevent a substantial fraction of infections. Planned interim analysis may provide conclusive evidence against the traditional null hypothesis without establishing substantial benefit. At this interim point, the Data and Safety Monitoring Board would then face the dilemma of knowing the product has some positive effect, but perhaps not as great an effect as the protocol has declared necessary. PURPOSE: In March 2008, NIH program staff recommended that the VOICE protocol team discuss the stopping rules with stakeholders prior to initiating the protocol. The goals of the workshop were to inform community representatives about the potential ethical dilemma associated with stopping rules and engage in dialogue about these issues. We describe the resulting community consultation and summarize the outcomes. METHODS: A 2-day workshop was convened with the goal of having a clear and transparent consultation with the stakeholders around the question, 'Given emerging evidence that a product could prevent some infections, would the community support a decision to continue accruing to the trial?' Participants included research staff and community stakeholders. Lectures with visual aids, discussions, and exercises using interactive learning tasks were used, with a focus on statistics and interpreting data from trials, particularly interim data. RESULTS: Results of oral and written evaluations by participants were reviewed. The feedback was mostly positive, with some residual confusion regarding statistical concepts. However, discussions with attendees later revealed that not all felt prepared to engage fully in the workshop. LIMITATIONS: This was the presenters' first experience facilitating a formal discussion with an audience that had no advanced science, research, or mathematics training. Community representatives' concern regarding speaking for their communities without consulting them also created a challenge for the workshop. CONCLUSIONS: Open discussion around trial stopping rules requires that all discussants have an understanding of trial design concepts and feel a sense of empowerment to ask and answer questions. The VOICE CWG workshop was a first step toward the goal of open discussion regarding trial stopping rules and interim results for the study; however, ongoing education and dialogue must occur to ensure that all stakeholders fully participate in the process.

Pooled Prevalence of Adverse Pregnancy and Neonatal Outcomes in Malawi, South Africa, Uganda, and Zimbabwe: Results From a Systematic Review and Meta-Analyses to Inform Trials of Novel HIV Prevention Interventions During Pregnancy.

BACKGROUND: Robust data summarizing the prevalence of pregnancy and neonatal outcomes in low- and middle-income countries are critically important for studies evaluating investigational products for HIV prevention and treatment in pregnant and breastfeeding women. In preparation for studies evaluating the safety of the dapivirine vaginal ring for HIV prevention in pregnancy, we conducted a systematic literature review and meta-analyses to summarize the prevalence of pregnancy and neonatal outcomes in Malawi, South Africa, Uganda, and Zimbabwe. METHODS: Ten individual systematic literature reviews were conducted to identify manuscripts presenting prevalence data for 12 pregnancy and neonatal outcomes [pregnancy loss, stillbirth, preterm birth, low birthweight (LBW), neonatal mortality, congenital anomaly, chorioamnionitis, postpartum endometritis, postpartum hemorrhage, gestational hypertension, preeclampsia/eclampsia, and preterm premature rupture of membranes (PPROM)]. Studies included in the meta-analyses were published between January 1, 1998, and July 11, 2018, provided numerator and denominator data to support prevalence estimation, and included women of any HIV serostatus. Random-effects meta-analyses were conducted to estimate the pooled prevalence and 95% confidence interval (CI) for each outcome overall, by country, and by HIV status. RESULTS: A total of 152 manuscripts were included across the 12 outcomes. Overall, the frequency of stillbirth (n = 75 estimates), LBW (n = 68), and preterm birth (n = 67) were the most often reported. However, fewer than 10 total manuscripts reported prevalence estimates for chorioamnionitis, endometritis, or PPROM. The outcomes with the highest pooled prevalence were preterm birth (12.7%, 95%CI 11.2-14.3), LBW (11.7%, 95%CI 10.6-12.9), and gestational hypertension (11.4%, 95%CI 7.8-15.7). Among the outcomes with the lowest pooled prevalence estimates were neonatal mortality (1.7%, 95%CI 1.4-2.1), pregnancy loss [1.9%, 95%CI 1.1-2.8, predominately studies (23/29) assessing losses occurring after the first trimester], PPROM (2.2%, 95%CI 1.5-3.2), and stillbirth (2.5%, 95%CI 2.2-2.7). CONCLUSIONS: Although this review identified numerous prevalence estimates for some outcomes, data were lacking for other important pregnancy-related conditions. Additional research in pregnant populations is needed for a thorough evaluation of investigational products, including for HIV prevention and treatment, and to inform better estimates of the burden of adverse pregnancy outcomes globally.

Prevalence and Incidence of Sexually Transmitted Infection in Injectable Progestin Contraception Users in South Africa.

Introduction: Whether intramuscular depot medroxyprogesterone acetate (DMPA-IM) and norethisterone enanthate (NET-EN) have a differential impact on the incidence of sexually transmitted infection (STI) remains unclear. In the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, HIV-1 acquisition was higher for DMPA-IM users vs. NET-EN users. We compared DMPA-IM and NET-EN users with regard to chlamydia, gonorrhea, trichomoniasis, syphilis, and herpes simplex virus type 2 (HSV-2) infection. Materials and Methods: Prospective data were analyzed from VOICE, a randomized trial of HIV-1 chemoprophylaxis. Participants were evaluated annually and as indicated for chlamydia, gonorrhea, trichomoniasis, and syphilis. Stored specimens were tested for HSV-2. Proportional hazards models compared the risk of STI between DMPA-IM and NET-EN users. Results: Among 2,911 injectable contraception users in South Africa, 1,800 (61.8%) used DMPA-IM and 1,111 used NET-EN (38.2%). DMPA-IM and NET-EN users did not differ in baseline chlamydia: 15.1 vs. 14.3%, p= 0.54; gonorrhea: 3.4 vs. 3.7%, p= 0.70; trichomoniasis: 5.7 vs.5.0%, p= 0.40; or syphilis: 1.5 vs. 0.7%, p= 0.08; but differed for baseline HSV-2: (51.3 vs. 38.6%, p < 0.001). Four hundred forty-eight incident chlamydia, 103 gonorrhea, 150 trichomonas, 17 syphilis, and 48 HSV-2 infections were detected over 2,742, 2,742, 2,783, 2,945, and 756 person-years (py), respectively (chlamydia 16.3/100 py; gonorrhea 3.8/100 py; trichomoniasis 5.4/100 py; syphilis 0.6/100 py; HSV-2 6.4/100 py). Comparing DMPA-IM with NET-EN users, no difference was noted in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV2 infections, including when adjusted for confounders [chlamydia (aHR 1.03, 95% CI 0.85-1.25), gonorrhea (aHR 0.88, 95% CI 0.60-1.31), trichomoniasis (aHR 1.07, 95% CI 0.74-1.54), syphilis (aHR 0.41, 95% CI 0.15-1.10), and HSV-2 (aHR 0.83, 95% CI 0.45-1.54, p= 0.56)]. Discussion: Among South African participants enrolled in VOICE, DMPA-IM and NETEN users differed in prevalence of HSV-2 at baseline but did not differ in the incidence of chlamydia, gonorrhea, trichomoniasis, syphilis, or HSV-2 infection. Differential HIV-1 acquisition, previously demonstrated in this cohort, does not appear to be explained by differential STI acquisition. However, the high incidence of multiple STIs reinforces the need to accelerate access to comprehensive sexual and reproductive health services.

Building a Global Evidence Base to Guide Policy and Implementation for Group Antenatal Care in Low- and Middle-Income Countries: Key Principles and Research Framework Recommendations from the Global Group Antenatal Care Collaborative.

Evidence from high-income countries suggests that group antenatal care, an alternative service delivery model, may be an effective strategy for improving both the provision and experience of care. Until recently, published research about group antenatal care did not represent findings from low- and middle-income countries, which have health priorities, system challenges, and opportunities that are different than those in high-income countries. Because high-quality evidence is limited, the World Health Organization recommends group antenatal care be implemented only in the context of rigorous research. In 2016 the Global Group Antenatal Care Collaborative was formed as a platform for group antenatal care researchers working in low- and middle-income countries to share experiences and shape future research to accelerate development of a robust global evidence base reflecting implementation and outcomes specific to low- and middle-income countries. This article presents a brief history of the Collaborative's work to date, proposes a common definition and key principles for group antenatal care, and recommends an evaluation and reporting framework for group antenatal care research.

Impact of group antenatal care (G-ANC) versus individual antenatal care (ANC) on quality of care, ANC attendance and facility-based delivery: A pragmatic cluster-randomized controlled trial in Kenya and Nigeria.

BACKGROUND: Low quality and frequency of antenatal care (ANC) are associated with lower uptake of facility-based deliveries-a key intervention to reduce maternal and neonatal mortality. We implemented group ANC (G-ANC), an alternative service delivery model, in Kenya and Nigeria, to assess its impact on quality and attendance at ANC and uptake of facility-based delivery. METHODS: From October 2016‒January 2018, we conducted a facility-based, pragmatic, cluster-randomized controlled trial with 20 clusters per country. We recruited women <24 weeks gestation during their first ANC visit and enrolled women at intervention facilities who agreed to attend G-ANC in lieu of routine individual ANC. The G-ANC model consisted of five monthly 2-hour meetings with clinical assessments alongside structured gestationally specific group discussions and activities. Quality of care was defined as receipt of eight specific ANC interventions. Data were obtained through facility records and self-report during a home-based postpartum survey. Analysis was by intention to treat. FINDINGS: All women who completed follow up are included in the analysis (Nigeria: 1018/1075 enrolled women [94.7%], Kenya: 826/1013 [81.5%]). In Nigeria women in the intervention arm were more likely to have a facility-based delivery compared to those in the control arm (Nigeria: 76.7% [391/510] versus 54.1% [275/508]; aOR 2.30, CI 1.51-3.49). In both countries women in the intervention arm were more likely than those in the control arm to receive quality ANC (Nigeria: aOR 5.8, CI 1.98-17.21, p<0.001; Kenya: aOR 5.08, CI 2.31-11.16, p<0.001) and to attend at least four ANC visits (Nigeria: aOR 13.30, CI 7.69-22.99, p<0.001; Kenya: aOR 7.12, CI 3.91-12.97, p<0.001). CONCLUSIONS: G-ANC was associated with higher facility-based delivery rates in Nigeria, where those rates associated with individual ANC were low. In both Kenya and Nigeria it was associated with a higher proportion of women receiving quality ANC and higher frequency of ANC visits.