Limiting adverse birth outcomes in resource-limited settings (LABOR): protocol of a prospective intrapartum cohort study.

Background: Each year, nearly 300,000 women and 5 million fetuses or neonates die during childbirth or shortly thereafter, a burden concentrated disproportionately in low- and middle-income countries. Identifying women and their fetuses at risk for intrapartum-related morbidity and death could facilitate early intervention. Methods: The Limiting Adverse Birth Outcomes in Resource-Limited Settings (LABOR) Study is a multi-country, prospective, observational cohort designed to exhaustively document the course and outcomes of labor, delivery, and the immediate postpartum period in settings where adverse outcomes are frequent. The study is conducted at four hospitals across three countries in Ghana, India, and Zambia. We will enroll approximately 12,000 women at presentation to the hospital for delivery and follow them and their fetuses/newborns throughout their labor and delivery course, postpartum hospitalization, and up to 42 days thereafter. The co-primary outcomes are composites of maternal (death, hemorrhage, hypertensive disorders, infection) and fetal/neonatal adverse events (death, encephalopathy, sepsis) that may be attributed to the intrapartum period. The study collects extensive physiologic data through the use of physiologic sensors and employs medical scribes to document examination findings, diagnoses, medications, and other interventions in real time. Discussion: The goal of this research is to produce a large, sharable dataset that can be used to build statistical algorithms to prospectively stratify parturients according to their risk of adverse outcomes. We anticipate this research will inform the development of new tools to reduce peripartum morbidity and mortality in low-resource settings.

Comprehensive pregnancy monitoring with a network of wireless, soft, and flexible sensors in high- and low-resource health settings.

Vital signs monitoring is a fundamental component of ensuring the health and safety of women and newborns during pregnancy, labor, and childbirth. This monitoring is often the first step in early detection of pregnancy abnormalities, providing an opportunity for prompt, effective intervention to prevent maternal and neonatal morbidity and mortality. Contemporary pregnancy monitoring systems require numerous devices wired to large base units; at least five separate devices with distinct user interfaces are commonly used to detect uterine contractility, maternal blood oxygenation, temperature, heart rate, blood pressure, and fetal heart rate. Current monitoring technologies are expensive and complex with implementation challenges in low-resource settings where maternal morbidity and mortality is the greatest. We present an integrated monitoring platform leveraging advanced flexible electronics, wireless connectivity, and compatibility with a wide range of low-cost mobile devices. Three flexible, soft, and low-profile sensors offer comprehensive vital signs monitoring for both women and fetuses with time-synchronized operation, including advanced parameters such as continuous cuffless blood pressure, electrohysterography-derived uterine monitoring, and automated body position classification. Successful field trials of pregnant women between 25 and 41 wk of gestation in both high-resource settings (n = 91) and low-resource settings (n = 485) demonstrate the system's performance, usability, and safety.

Wireless skin sensors for physiological monitoring of infants in low-income and middle-income countries.

Globally, neonatal mortality remains unacceptability high. Physiological monitoring is foundational to the care of these vulnerable patients to assess neonatal cardiopulmonary status, guide medical intervention, and determine readiness for safe discharge. However, most existing physiological monitoring systems require multiple electrodes and sensors, which are linked to wires tethered to wall-mounted display units, to adhere to the skin. For neonates, these systems can cause skin injury, prevent kangaroo mother care, and complicate basic clinical care. Novel, wireless, and biointegrated sensors provide opportunities to enhance monitoring capabilities, reduce iatrogenic injuries, and promote family-centric care. Early validation data have shown performance equivalent to (and sometimes exceeding) standard-of-care monitoring systems in premature neonates cared for in high-income countries. The reusable nature of these sensors and compatibility with low-cost mobile phones have the future potential to enable substantially lower monitoring costs compared with existing systems. Deployment at scale, in low-income countries, holds the promise of substantial improvements in neonatal outcomes.

Adolescent and young adult couples' views of intravaginal practices: a qualitative analysis of a pilot study.

PURPOSE: In this study, we evaluated the risk behaviors that are drivers of the HIV epidemic among adolescent girls and young women in Zambia using a focus group research technique. SUBJECTS AND METHODS: Eighteen adolescent couples (n=18 females and 18 males) aged 16-24 participated in six focus groups discussions (3 per gender) convened at three health facilities in Lusaka, Zambia. Focus group moderators utilized a set of open-ended questions to guide the 60-minute sessions. The focus group audio recordings were transcribed, coded, and analyzed using qualitative content analysis in Nvivo 11. RESULTS: Three themes and four subthemes were identified relating to adolescent and young adult couples' knowledge, views, and male partner attitudes toward intravaginal practices (IVPs). The first theme, knowledge and rationale for IVPs, consisted of the subthemes relating to why adolescents and young adult couples engage in IVPs and assessed their knowledge of health risks associated with IVPs. The second theme, attitudes toward IVPs, consisted of the subtheme willingness to stop or support partner to discontinue IVP and practices toward IVP and strategies for changing. The third theme, strategies for changing IVPs, consisted of the subtheme raise awareness. CONCLUSION: IVPs used for cleaning purposes were perceived as essential to enhancing hygiene, health, and sexual satisfaction for both girls and boys. However, couples expressed concern about the health effects of IVPs used for tightening and a desire for learning more about this practice as well as stopping it.

Influencing the importance of health, partners, and hygiene among Zambian women.

Intravaginal practices (IVPs) are common in Zambia and are usually practiced for hygiene, partner pleasure, and health. IVPs are associated with HIV acquisition, changes in the vaginal flora, and bacterial vaginosis (BV), making it important to understand the decision-making process behind IVP engagement. The Women's and Sexual Health (WASH) intervention decreased IVP engagement among HIV-infected Zambian women, though change in reasons for engagement has not been assessed. We used conjoint analysis (CA) to quantify the decision-making process of IVP engagement and evaluated how the WASH intervention impacted these factors. Participants were N = 84 women (37 ± 8 years old) randomized to WASH (n = 46) or standard of care plus (SOC+; n = 38) who completed demographic measures and a CA questionnaire at baseline, six months, and 12 months to quantify the importance placed on hygiene, partner pleasure, and health. The importance placed on health increased from baseline to six months (15.5 versus 25.1; p < 0.001) and from baseline to 12 months (15.5 versus 50.5; p < 0.001), and was higher in SOC+ at six months (19.9 versus 30.3; p = 0.003). Hygiene importance decreased from baseline (63.6) to six months (50.3), and from baseline to 12 months (26.1), and was higher in the experimental arm at six months (56.1) compared to SOC+ (44.6; p = 0.029). Importance placed on partner pleasure did not change over time in either group. Findings suggest that both groups exhibited an increase in the importance placed on health and a decrease on hygiene importance for IVP engagement, suggesting that SOC+ may be sufficient to promote attitude changes that may facilitate IVP discontinuation and may prove to be more cost effective by using fewer monetary resources. Findings highlight the potential of interventions to influence attitudes toward IVPs and provide novel avenues for research to improve the design and conduct of interventions aimed at reducing IVPs among Zambian women and contribute to HIV prevention efforts.

Intravaginal practices among young HIV-infected women in Lusaka, Zambia.

Intravaginal practices (IVP) are linked to bacterial vaginosis (BV), obstetric/gynecological complications, and HIV. Late adolescent and young adult (LAYA) women in Zambia have high rates of HIV. Adult and mature (AM) HIV-infected women in Zambia engage in IVP for hygiene, health, and sexuality reasons; however, to our knowledge, IVP use among LAYA women has not been examined. This study compares IVP use between LAYA and AM women to identify age-specific factors to target when developing IVP reduction interventions for LAYA women. LAYA (≤25 years; n = 24) and AM (>25 years; n=124) HIV-infected women completed self-administered demographic, HIV history, sexual risk factor, and IVP measures. LAYA and AM women were then compared. Number of sexual partners, sexual activity, or condom use did not differ between groups. Rates of IVP in the prior month with different products were similar, though LAYA women used soap more frequently (96% versus 74.2%, p = 0.034). LAYA women were more likely to use products for hygiene reasons (soap 83% versus 43%; cloth, paper, or wipes 50% versus 17%, p < 0.05); and AM women to use products to please sexual partners (cloth 20% versus 56%, p = 0.074). Interventions tailored to LAYA women may be needed to reduce IVP and subsequent BV as LAYA women may have different reasons for engaging in IVP, in comparison with AM women. Reduced IVP among LAYA women may decrease the risk for HIV transmission to sexual partners and newborns and is urgently needed in settings with high prevalence of IVP, BV, and HIV infections, such as Zambia.

A bio-behavioral intervention to decrease intravaginal practices and bacterial vaginosis among HIV infected Zambian women, a randomized pilot study.

BACKGROUND: Intravaginal practices (IVP) (cleansing or introducing products inside the vagina for hygiene, health or to please sexual partners) are common among women with HIV. IVP increase the risk of developing bacterial Vaginosis (BV), the most common genital infection associated with transmission of sexually transmitted infections and HIV. This study tested a pilot intervention to reduce IVP and BV in HIV infected women in Zambia. METHODS: One hundred twenty-eight HIV infected women engaging in IVP were randomized to two conditions: enhanced standard of care (n = 70) and experimental (n = 58) from May 1, 2013 to February 28, 2014. All participants received a brief educational counseling session on discontinuation of IVP, and those with BV, were provided with medical treatment for BV. Women in the experimental condition received an additional group-based, culturally tailored intervention. Participants completed questionnaires assessing sexual risk factors and IVP and were assessed for BV using Nugent criteria at baseline, 6 months and 12 months. RESULTS: At 12-month, the proportion of self-reported use of IVPs decreased in the experimental condition: soap (28% vs. 47%); cloth or a rag (19% vs. 38%); and traditional medicines (22% vs. 42%) (all p < 0.05)) compared with the enhanced standard of care condition. The prevalence of BV at 6 and 12 months did not differ by study condition but averaging over study condition, prevalence of BV decreased from 64.2% at baseline to 15.6% at 6 months (p < 0.01) and to 23.6% at 12 months (p = 0.15). Using an enhanced standard of care approach and an enhanced standard of care + a group intervention, IVP and BV decreased over time, but the experimental condition had greater reduction in self-reported use of IVP. CONCLUSIONS: Future studies should address interventions in communities with high burden of IVP, BV and HIV. Interventions that could be administered during routine medical care and decrease IVP and BV are needed, and should be considered part of women's health programs. TRIAL REGISTRATION NUMBER: NCT03134924 (retrospectively registered 21st April 2017).

Determinants of intravaginal practices among HIV-infected women in Zambia using conjoint analysis.

Intravaginal practices (IVPs) are associated with an increased risk of bacterial vaginosis and may play a role in HIV transmission. The objective of this study was to identify the importance of factors underlying the decision to engage in IVP using conjoint analysis; a novel statistical technique used to quantify health-related decisions. This study was a cross-sectional study. HIV-infected women in Zambia completed audio computer-administered self-interview questionnaires assessing demographic, risk factors and IVPs. Reasons for engaging in IVPs were explored using conjoint questionnaires. Conjoint analysis was used to identify the relative importance of factors for engaging in IVPs. Results of the conjoint analysis demonstrated that hygiene was the most important reason for engaging in IVPs (mean importance score = 61, SD = 24.3) followed by partner's preference (mean importance score = 20, SD = 14.4) and health (mean importance score = 17, SD = 13.5). When making the decision to engage in IVPs, women rank the importance of hygiene, partner preference and health differently, according to their personal characteristics. The use of conjoint analysis to define the characteristics of women more likely to engage in specific practices should be used to develop tailored rather than standardised IVP interventions, and such interventions should be incorporated into clinical practice and women's health programmes.

A cross-sectional study of bacterial vaginosis, intravaginal practices and HIV genital shedding; implications for HIV transmission and women's health.

OBJECTIVES: Bacterial vaginosis (BV) is associated with an increased risk of HIV transmission, and intravaginal practices (IVP) are an important risk factor for developing BV. The relationship between IVP, BV and HIV lower genital shedding, responsible for HIV transmission, has not been examined in women receiving antiretrovirals in Zambia. DESIGN: Cross-sectional study. SETTING: Community Health Center in Lusaka, Zambia. PARTICIPANTS AND METHODS: Participants were HIV-infected women receiving antiretroviral therapy and engaging in IVP (n=128). Participants completed audio computer-administered self-interviews to assess IVP and underwent a vaginal examination. BV was diagnosed using Nugent criteria. HIV-1 lower genital shedding was assessed by measuring HIV-1 RNA in cervicovaginal lavages. RESULTS: Most women engaged in IVP daily (114, 89.0%) and 81 (63.3%) of the participants had BV. HIV-1 genital shedding was detected in 18 (14.2%) participants. BV was associated with daily use of IVP (prevalence ratio, PR=4.58, CI 1.26 to 16.64, p=0.02) and weekly use of traditional medicines for IVP (PR=1.33, CI 1.05 to 1.68, p=0.02). The only factor associated with HIV-1 lower genital shedding was plasma viraemia (PR=4.61, CI 2.02 to 10.54, p<0.001). Neither IVP nor BV were associated with HIV shedding. CONCLUSIONS: Despite the frequency of IVP and high prevalence of BV, plasma viraemia was the primary factor associated with HIV lower genital shedding. These findings support early initiation of antiretrovirals as an HIV prevention tool. Given adverse health outcomes associated with BV, the association between frequent IVP and BV, and the powerful local norms and traditions encouraging IVP, there is a need for studies assessing culturally tailored interventions to decrease BV in high-prevalence settings.

Injectable and oral contraceptives and risk of HIV acquisition in women: an analysis of data from the MDP301 trial.

STUDY QUESTION: Do injectable and oral contraceptives increase the risk of human immunodeficiency virus (HIV) acquisition in women? SUMMARY ANSWER: After adjusting for confounders, evidence of a significantly increased risk of HIV remained for women using injectable depo-medroxyprogesterone (DMPA) (hazard ratio = 1.49, 95% confidence interval (1.06-2.08)) but not for injectable norethisterone-enanthate (Net-En) or oral contraceptive pills (OC). WHAT IS KNOWN ALREADY: An association between the use of some types of hormonal contraception (HC) methods and an increased risk of HIV, possibly through changes in the genital tract environment and alterations in the immune response, has been previously observed, although not consistently. A recent systematic review of these studies has highlighted the need for more definitive evidence. STUDY DESIGN, SIZE, DURATION: A secondary data analysis of the MDP301 phase 3 microbicide trial was conducted to estimate the effects of use of different methods of HC on the risk of HIV acquisition in women. HIV-negative women (n = 8663) with a median age of 28 years were included in the analysis; 382 HIV seroconverted by 52 weeks follow-up; 10% of women-years were lost to follow-up before 52 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: Contraceptive use was reported at each 4-weekly visit. Cox proportional hazards (PH) models were used to estimate the effects of baseline and current use of injectable DMPA, injectable Net-En and OC compared with no HC, on the risk of HIV, adjusting for baseline and time-updated covariates. Causal effects for 52 weeks of HC use compared with no HC were estimated in a weighted Cox model, censoring women at deviation from baseline HC use (or non-use) or pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, 2499 (29%) women were on DMPA, 1180 (14%) on Net-En, and 1410 (16%) on OC; 3574 (40%) not on HC, started HC in follow-up. Adjusted hazard ratios (HR) for baseline HC use, compared with no HC, were 1.38 (95% confidence interval (CI) 1.07-1.78) for DMPA; 1.18 (0.86-1.62) for Net-En and 0.97 (0.68-1.38) for OC. The estimated causal effects of DMPA and Net-En over 52 weeks were: HR = 1.49 (95% CI 1.06-2.08) and HR = 1.31 (95% CI 0.62-1.61), respectively. LIMITATIONS, REASONS FOR CAUTION: A main limitation of the study was that it was a secondary analysis of data from a study that was not designed to investigate this question. Despite our best efforts, we cannot exclude residual confounding to explain the effect of DMPA. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study should be reviewed by the World Health Organization to determine whether current recommendations on the use of DMPA in settings with high HIV prevalence require modification. STUDY FUNDING/COMPETING INTERESTS: MDP is a partnership of African and European academic/government institutions with commercial organizations, which is funded by the UK Government (DFID and MRC), with support from IPM and EDCTP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: None.

Examining targets for HIV prevention: intravaginal practices in Urban Lusaka, Zambia.

Intravaginal practices (IVP) are the introduction of products inside the vagina for hygienic, health, or sexuality reasons. The influence of men and Alengizis, traditional marriage counselors for girls, in promoting IVP has not been explored. We conducted gender-concordant focus groups and key informant interviews with Alengizis. The responses were conducted grouped into three themes: (1) cultural norms, (2) types and reasons for IVP, and (3) health consequences. We found that IVP were used by all participants in our sample and were taught from generation to generation by friends, relatives, or Alengizis. The reasons for women to engage in IVP were hygienic, though men expect women to engage in IVP to enhance sexual pleasure. Approximately 40% of women are aware that IVP can facilitate genital infections, but felt they would not feel clean discontinuing IVP. All men were unaware of the vaginal damage caused by IVP, and were concerned about the loss of sexual pleasure if women discontinued IVP. Despite the health risks of IVP, IVP continue to be widespread in Zambia and an integral component of hygiene and sexuality. The frequency of IVP mandates exploration into methods to decrease or ameliorate their use as an essential component of HIV prevention.

PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial.

BACKGROUND: Innovative prevention strategies for HIV-1 transmission are urgently needed. PRO2000 vaginal gel was efficacious against HIV-1 transmission in studies in macaques; we aimed to assess efficacy and safety of 2% and 0·5% PRO2000 gels against vaginal HIV-1 transmission in women in sub-Saharan Africa. METHODS: Microbicides Development Programme 301 was a phase 3, randomised, double-blind, parallel-group trial, undertaken at 13 clinics in South Africa, Tanzania, Uganda, and Zambia. We randomly assigned sexually active women, aged 18 years or older (≥16 years in Tanzania and Uganda) without HIV-1 infection in a 1:1:1 ratio to 2% PRO2000, 0·5% PRO2000, or placebo gel groups for 52 weeks (up to 104 weeks in Uganda). Randomisation was done by computerised random number generator. Investigators and participants were masked to group assignment. The primary efficacy outcome was incidence of HIV-1 infection before week 52, which was censored for pregnancy and excluded participants without HIV-1 follow-up data or with HIV-1 infection at enrolment. HIV-1 status was established by rapid tests or ELISA at screening at 12 weeks, 24 weeks, 40 weeks, and 52 weeks, and confirmed in a central reference laboratory. The primary safety endpoint was an adverse event of grade 3 or worse. Use of 2% PRO2000 gel was discontinued on Feb 14, 2008, on the recommendation of the Independent Data Monitoring Committee because of low probability of benefit. This trial is registered at http://isrctn.org, number ISRCTN 64716212. FINDINGS: We enrolled 9385 of 15 818 women screened. 2591 (95%) of 2734 participants enrolled to the 2% PRO2000 group, 3156 (95%) of 3326 in the 0·5% PRO2000 group, and 3112 (94%) of 3325 in the placebo group were included in the primary efficacy analysis. Mean reported gel use at last sex act was 89% (95% CI 86-91). HIV-1 incidence was much the same between groups at study end (incidence per 100 woman-years was 4·5 [95% CI 3·8-5·4] for 0·5% PRO2000 vs 4·3 [3·6-5·2] for placebo, hazard ratio 1·05 [0·82-1·34], p=0·71), and at discontinuation (4·7 [3·8-5·8] for 2% PRO2000 gel, 3·9 [3·0-4·9] for 0·5% PRO2000 gel, and 3·9 [3·1-5·0] for placebo gel). Incidence of the primary safety endpoint at study end was 4·6 per 100 woman-years (95% CI 3·9-5·4) in the 0·5% PRO2000 group and 3·9 (3·2-4·6) in the placebo group; and was 4·5 (3·7-5·5) in the 2% PRO2000 group at discontinuation. INTERPRETATION: Although safe, 0·5% PRO2000 and 2% PRO2000 are not efficacious against vaginal HIV-1 transmission and are not indicated for this use. FUNDING: UK Department for International Development, UK Medical Research Council, European and Developing Countries Clinical Trials Partnership, International Partnership for Microbicides, and Endo Pharmaceuticals Solutions.

Priorities for antiretroviral therapy research in sub-Saharan Africa: a 2002 consensus conference in Zambia.

BACKGROUND: A consensus conference was held to discuss priorities for antiretroviral therapy (ART) research in Zambia, one of the world's most heavily HIV-afflicted nations. Zambia, like other resource-limited settings, has increasing access to highly active antiretroviral therapy (HAART) because of declining drug costs, use of government-purchased generic medications, and increased global donations. For sustained delivery of care with HAART in a resource-constrained medical and public health context, operational research is required and clinical trials are desirable. The priority areas for research are most relevant today given the increasing availability of HAART. METHODS: A conference was held in Lusaka, Zambia, in January 2002 to discuss priority areas for ART research in Zambia, with participants drawn from a broad cross section of Zambian society. State-of-the-art reviews and 6 intensive small group discussions helped to formulate a suggested research agenda. RESULTS: Conference participants believed that the most urgent research priorities were to assess how therapeutic resources could be applied for the greatest overall benefit and to minimize the impact of nonadherence and viral resistance. Identified research priorities were as follows:Conference participants recommended that HIV-related clinical care and research be integrated within home-based care services and operated within the existing health delivery structures to ensure sustainability, reduce costs, and strengthen the structures. CONCLUSION: Our consensus was that antiretroviral clinical trials and operational research are essential for Zambia to address the new challenges arising from increasing ART availability. There is global consensus that antiretroviral clinical trials in resource-constrained countries are possible, and the capacity for such trials should be developed further in Africa.