Understanding the role of men in women's use of the vaginal ring and oral PrEP during pregnancy and breastfeeding: multi-stakeholder perspectives.

We examined men's influence on women's interest in biomedical HIV prevention during pregnancy and breastfeeding through structured questionnaires and focus group discussions with currently or recently pregnant and breastfeeding (P/BF) women (n = 65), men with P/BF partners (n = 63) and mothers/mothers-in-law of P/BF women (n = 68) in eastern and southern Africa. Data were transcribed, coded and summarised into analytical memos. Men were depicted by most participants as joint decision-makers and influencers of women's use of HIV prevention. Cultural and religious norms depicting men as heads, breadwinners and protectors of the family were cited to legitimise their involvement in decision-making. Male partner education and engagement were recommended to garner their support in women's HIV prevention. This study elucidates how P/BF women's ability to prevent HIV is shaped by traditional and contemporary gender norms in social settings and locations where the study was conducted. Findings may aid intervention design to engage men for P/BF women's effective use of microbicide and oral PrEP.

Mid-thigh circumference as an indicator of nutritional status to predict adverse pregnancy outcomes among HIV-infected and HIV-uninfected women in Malawi.

BACKGROUND: High rates of adverse pregnancy outcomes globally raise the need to understand risk factors and develop preventative interventions. The Pregnancy Outcomes in the Era of Universal Antiretroviral Treatment in Sub-Saharan Africa (POISE Study) was a prospective, observational cohort study conducted from 2016 to 2017 in Blantyre, Malawi. We examine the associations between indicators of nutritional status, specifically mid-thigh circumference (MTC) and body-mass index (BMI), and adverse pregnancy outcomes, low birth weight (LBW), preterm birth (PTB), and small-for-gestational age (SGA), in a cohort of HIV-infected and HIV-uninfected women. METHODS: Sociodemographic, clinical, laboratory, and maternal height, weight and MTC data were collected immediately before or after delivery at the Queen Elizabeth Central Hospital (QEHC) and 4 affiliated health centers in Blantyre, Malawi. LBW was defined as birth weight < 2.5 kg; PTB as gestational age < 37 weeks using Ballard score; and SGA as birth weight < 10th percentile for gestational age. Descriptive, stratified, and multivariable logistic regression were conducted using R. RESULTS: Data from 1298 women were analyzed: 614 HIV-infected and 684 HIV-uninfected. MTC was inversely associated with LBW (adjusted odds ratio [aOR] = 0.95, p = 0.03) and PTB (aOR 0.92, p < 0.001), after controlling for HIV status, age, socioeconomic status and hemoglobin. The association between MTC and SGA was (aOR 0.99, p = 0.53). Similarly, higher BMI was significantly associated with lower odds of PTB (aOR 0.90, p < 0.001), LBW (aOR 0.93, p = 0.05), and SGA (aOR 0.95, p = 0.04). CONCLUSIONS: We observed an inverse relationship between MTC and adverse pregnancy outcomes in Malawi irrespective of HIV infection. MTC performs comparably to BMI; the ease of measuring MTC could make it a practical tool in resource-constrained settings for identification of women at risk of adverse pregnancy outcomes.

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa.

BACKGROUND: Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW). METHODS: Directly observed PrEP was administered for 12 weeks in a pregnancy (14-24 weeks' gestation, n = 20) and postpartum (6-12 weeks postpartum, n = 20) group of AGYW aged 16-24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography-tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated. RESULTS: Median age was 20 (IQR, 19-22) years. Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median (IQR) half-life was 10 (7-12) days in pregnancy and 17 (14-21) days postpartum, with steady state achieved by 5 and 8 weeks, respectively. Observed median (IQR) steady-state TFV-DP was 965 fmol/punch (691-1166) in pregnancy versus 1406 fmol/punch (1053-1859) postpartum (P = .006). Modeled median steady-state TFV-DP was 881 fmol/punch (667-1105) in pregnancy versus 1438 fmol/punch (1178-1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations. CONCLUSIONS: TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. These Population-specific benchmarks can be used to guide PrEP adherence support in pregnant/postpartum African women. CLINICAL TRIALS REGISTRATION: NCT03386578.

After their wives have delivered, a lot of men like going out: Perceptions of HIV transmission risk and support for HIV prevention methods during breastfeeding in sub-Saharan Africa.

Female-initiated HIV prevention methods, such as oral pre-exposure prophylaxis (PrEP) and the vaginal ring, may be important risk reduction strategies for breastfeeding women. Given their novelty, information about the sociocultural context and how it influences perceptions of and support for their use during breastfeeding is lacking. To address this gap, we conducted 23 focus group discussions separately with pregnant and breastfeeding women, male partners and grandmothers (N = 196) and 36 in-depth interviews with key informants in Malawi, South Africa, Uganda and Zimbabwe. We analysed the data using a framework analysis method. Overall, breastfeeding was the norm, and participants described the transference of health (e.g., nutrition) and disease (e.g., HIV) to children through breast milk. Participants considered the early breastfeeding period as one of high HIV transmission risk for women. They explained that male partners tend to seek outside sexual partners during this period because women need time to recover from delivery, women focus their attention on the child, and some men are disgusted by breast milk. Participants highlighted concerns about the drugs in oral PrEP transferring to the child through breast milk, but fewer worried about the effects of the vaginal ring because the drug is localized. Women, grandmothers and key informants were supportive of women using these HIV prevention methods during breastfeeding, while male partners had mixed opinions. These findings can be used to tailor messages for promoting the use of PrEP or the vaginal ring during breastfeeding in sub-Saharan Africa.

Interventions to reduce preterm birth and stillbirth, and improve outcomes for babies born preterm in low- and middle-income countries: A systematic review.

BACKGROUND: Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required. METHODS: A systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted. RESULTS: 179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions. CONCLUSIONS: Evidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts.

Influences on willingness to use vaginal or oral HIV PrEP during pregnancy and breastfeeding in Africa: the multisite MAMMA study.

INTRODUCTION: Women in sub-Saharan Africa spend a substantial portion of their reproductive lives pregnant and/or breastfeeding (P/BF), yet they have limited options to prevent HIV during these maternal stages. In preparation for phase 3b prevention trials in P/BF women, we explored attitudes about using a vaginal ring or oral pills for pre-exposure prophylaxis (PrEP), perceptions of HIV risk during P/BF and key influences on future PrEP use. METHODS: In 2018, we conducted 16 single-sex focus group discussions (FGDs) with community- and clinic-recruited HIV-uninfected women, currently or recently P/BF, aged 18 to 40, and men with (currently or recently) P/BF partners, aged 18+. Participants completed a behavioural questionnaire, viewed an educational video and handled prototype placebo products. FGDs were conducted in local languages and transcribed, coded and analysed, using a socio-ecological framework, for key influences on willingness to use products, HIV risk perceptions and opinions on product attributes. RESULTS: Of the 128 participants (65 women, 63 men) 75% lived with their partner and 84% had a child. Women reported the most important influencers when P/BF were partners, and all stated that health decisions when P/BF are typically made jointly (e.g. medication use; ante/postnatal and baby care). There was consensus that P/BF women are at high risk for HIV, primarily because of their partner's infidelities, and new prevention options were welcomed. Participants valued multiple options and stated that woman's personal preference would be key to product choice. Anticipated concerns about products included risk of miscarriage, impact on infant development, complications during delivery and adequate production or taste of breastmilk. Specific perceived disadvantages emerged for the ring (e.g. vaginal discomfort, difficulty inserting/removing) and for pills (e.g. nausea/vomiting) that may be exacerbated during pregnancy. Health care providers' (HCPs) knowledge and approval of product use during P/BF was needed to mitigate anticipated fears. CONCLUSIONS: Participants perceived pregnancy and breastfeeding as high HIV risk periods and valued new prevention options. HIV protection of the mother-child dyad, safety of the baby, and ultimately, health of the family were paramount. Endorsement by HCPs and support from partners were key to future product acceptance. Participants recommended involving partners and HCPs in sensitization efforts for future trials.

Resumption of postpartum sexual activity and menses among HIV-infected women on lifelong antiretroviral treatment compared to HIV-uninfected women in Africa.

OBJECTIVE: To determine time from delivery to resumption of sexual activity and menses among HIV-infected women on antiretroviral treatment (ART) and HIV-uninfected women. METHODS: HIV-infected women on ART and HIV-uninfected women were recruited from five health facilities at delivery and followed prospectively for a maximum of 1 year in Blantyre, Malawi from January 2016 to September 2017. Sociodemographic, clinical, and laboratory data were collected at delivery and 1.5, 3, 6, 9, and 12 months. Descriptive, time to event Kaplan-Meier, and multivariable Cox proportional hazards analyses were conducted. RESULTS: Data on 878 women (460 [52.4%] HIV-uninfected and 418 [47.6%] HIV-infected, P=0.156) who attended at least one follow-up visit were analyzed. Among HIV-uninfected compared to HIV-infected women, respectively, the median number of days to resumption of sexual activity was 180 vs 181; to irregular menses was 82 vs 71; and to regular menses was 245 vs 366. In multivariable models, being married was associated with early resumption of sexual activity (hazard ratio [HR] 1.91, P<0.001), and being HIV-infected and use of an effective method of family planning were associated with later start of regular menses (HR<1.0, P<0.050). CONCLUSION: Counseling of women on reproductive intentions should start early irrespective of HIV infection or use of ART.

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery.

BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics. RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events. CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.).

Use of effective family planning methods and frequency of sex among HIV-infected and HIV-uninfected African women.

BACKGROUND: Frequency of sex, contraceptive use and HIV infection are key determinants of fertility. Use of an effective family planning (EFP) method (injectable, oral, intra-uterine contraceptive device (IUCD), or Norplant) potentially eliminates women's concerns of unintended pregnancy. We report the association between EFP and frequency of sex among HIV-infected and HIV-uninfected non-pregnant African women. METHODS: Prospective fertility intentions study nested within a phase 3 randomized double-masked placebo-controlled trial (2003-2005) to treat genital tract infections in HIV-infected and HIV-uninfected non-pregnant women. Enrollment of study participants was stratified by HIV infection status. Data on demographics, family planning and sexual history were obtained at baseline and at 3, 6, 9 and 12 months. Chi square and Wilcoxon Rank-Sum tests were used to compare categorical and continuous variables, respectively. Generalized Estimating Equations method was used to estimate relative risk (RR) of frequent sex (≥ 2 acts/week) among users of different EFP methods (injectable, oral, implant or intra-uterine contraceptive device). RESULTS: After adjusting for age, current health status, and fertility intentions, EFP use was significantly associated with frequent sex among HIV-infected women (RR 1.32; 95% Confidence Interval [CI] 1.14-1.52); this association was not statistically significant among HIV-uninfected women (RR 1.10; 95% CI 0.96-1.24). Fertility intentions among HIV-infected, and education among HIV-uninfected womenwere independent predictors of sex frequency. CONCLUSION: These data suggest that the association between EFP use and frequency of sex among women varies by HIV infection status. Service-delivery of diverse EFP methods should be integrated within HIV counseling, testing and treatment facilities. TRIAL REGISTRATION: Registration number NCT00140764 under the clinicaltrials.gov, first Posted: September 1, 2005, last Update Posted: August 10, 2011.

Standardizing the measurement of maternal morbidity: Pilot study results.

OBJECTIVE: To field test a standardized instrument to measure nonsevere morbidity among antenatal and postpartum women. METHODS: A cross-sectional study was conducted in Jamaica, Kenya, and Malawi (2015-2016). Women presenting for antenatal care (ANC) or postpartum care (PPC) were recruited if they were at least 28 weeks into pregnancy or 6 weeks after delivery. They were interviewed and examined by a doctor, midwife, or nurse. Data were collected and securely stored electronically on a WHO server. Diagnosed conditions were coded and summarized using ICD-MM. RESULTS: A total of 1490 women (750 ANC; 740 PPC) averaging 26 years of age participated. Most women (61.6% ANC, 79.1% PPC) were healthy (no diagnosed medical or obstetric conditions). Among ANC women with clinical diagnoses, 18.3% had direct (obstetric) conditions and 18.0% indirect (medical) problems. Prevalences among PPC women were lower (12.7% and 8.6%, respectively). When screening for factors in the expanded morbidity definition, 12.8% (ANC) and 11.0% (PPC) self-reported exposure to violence. CONCLUSION: Nonsevere conditions are distinct from the leading causes of maternal death and may vary across pregnancy and the puerperium. This effort to identify and measure nonsevere morbidity promotes a comprehensive understanding of morbidity, incorporating maternal self-reporting of exposure to violence, and mental health. Further validation is needed.

Prophylactic antibiotics to reduce pelvic infection in women having miscarriage surgery - The AIMS (Antibiotics in Miscarriage Surgery) trial: study protocol for a randomized controlled trial.

BACKGROUND: The estimated annual global burden of miscarriage is 33 million out of 210 million pregnancies. Many women undergoing miscarriage have surgery to remove pregnancy tissues, resulting in miscarriage surgery being one of the most common operations performed in hospitals in low-income countries. Infection is a serious consequence and can result in serious illness and death. In low-income settings, the infection rate following miscarriage surgery has been reported to be high. Good quality evidence on the use of prophylactic antibiotics for surgical miscarriage management is not available. Given that miscarriage surgery is common, and infective complications are frequent and serious, prophylactic antibiotics may offer a simple and affordable intervention to improve outcomes. METHODS: Eligible patients will be approached once the diagnosis of miscarriage has been made according to local practice. Once informed consent has been given, participants will be randomly allocated using a secure internet facility (1:1 ratio) to a single dose of oral doxycycline (400 mg) and metronidazole (400 mg) or placebo. Allocation will be concealed to both the patient and the healthcare providers. A total of 3400 women will be randomised, 1700 in each arm. The medication will be given approximately 2 hours before surgery, which will be provided according to local practice. The primary outcome is pelvic infection 2 weeks after surgery. Women will be invited to the hospital for a clinical assessment at 2 weeks. Secondary outcomes include overall antibiotic use, individual components of the primary outcome, death, hospital admission, unplanned consultations, blood transfusion, vomiting, diarrhoea, adverse events, anaphylaxis and allergy, duration of clinical symptoms, and days before return to usual activities. An economic evaluation will be performed to determine if prophylactic antibiotics are cost-effective. DISCUSSION: This trial will assess whether a single dose of doxycycline (400 mg) and metronidazole (400 mg) taken orally 2 hours before miscarriage surgery can reduce the incidence of pelvic infection in women up to 2 weeks after miscarriage surgery. TRIAL REGISTRATION: Registered with the ISRCTN (international standard randomised controlled trial number) registry: ISRCTN 97143849 . (Registered on April 17, 2013).

Maternal morbidity measurement tool pilot: study protocol.

BACKGROUND: While it is estimated that for every maternal death, 20-30 women suffer morbidity, these estimates are not based on standardized methods and measures. Lack of an agreed-upon definition, identification criteria, standardized assessment tools, and indicators has limited valid, routine, and comparable measurements of maternal morbidity. The World Health Organization (WHO) convened the Maternal Morbidity Working Group (MMWG) to develop standardized methods to improve estimates of maternal morbidity. To date, the MMWG has developed a definition and provided input into the development of a set of measurement tools. This protocol outlines the pilot test for measuring maternal morbidity in antenatal and postnatal clinical populations using these new tools. METHODS: In each setting, the tools will be piloted on approximately 250 women receiving antenatal care (ANC) (at least 28 weeks pregnant) and 250 women receiving postpartum care (PPC) (at least 6 weeks postpartum). The tools will be administered by trained health care workers. Each tool has three modules as follows: 1. personal history - socio-economic information, and risk-factors (such as violence and substance abuse) 2. patient symptoms - WHO Disability Assessment Schedule (WHODAS) 12-item, and mental health questionnaires, General Anxiety Disorder, 7-item (GAD-7) and Personal Health Questionnaire, 9-item (PHQ-9) 3. physical examination - signs, laboratory tests and results. DISCUSSION: This pilot (planned for Jamaica, Kenya and Malawi) will allow for comparing the types of morbidities women experience between and across settings, and determine the feasibility, acceptability and utility of using a modified, streamlined tool for routine measurement and summary estimates of morbidity to inform resource allocation and service provision. As part of the post-2015 Sustainable Development Goals (SDGs) estimating and measuring maternal morbidity will be essential to ensure appropriate resources are allocated to address its impact and improve well-being.

Using patient-held records to evaluate contraceptive use in Malawi.

OBJECTIVE: To investigate a method of using patient-held records to collect contraception data in Malawi, that could be used to explore contraceptive discontinuation and method switching. METHODS: In 2012, all 7393 women aged 15 to 49 years living in the area covered by the Karonga demographic surveillance site were offered a family planning card, which was attached to the woman's health passport - a patient-held medical record. Health-care providers were trained to use the cards to record details of contraception given to women. During the study, providers underwent refresher training sessions and received motivational text messages to improve data completeness. After one year, the family planning cards were collected for analysis. FINDINGS: Of the 7393 eligible women, 6861 (92.8%) received a family planning card and 4678 (63.3%) returned it after one year. Details of 87.3% (2725/3122) of contacts between health-care providers and the women had been recorded by health-care providers on either family planning cards or health passports. Lower-level health-care providers were more diligent at recording data on the family planning cards than higher-level providers. CONCLUSION: The use of family planning cards was an effective way of recording details of contraception provided by family planning providers. The involvement of health-care providers was key to the success of this approach. Data collected in this way should prove helpful in producing accurate estimates of method switching and the continuity of contraceptive use by women.

Exploring barriers to the delivery of cervical cancer screening and early treatment services in Malawi: some views from service providers.

BACKGROUND: Cervical cancer is the most common reproductive health cancer in Malawi. In most cases, women report to health facilities when the disease is in its advanced stage. In this study, we investigate service providers' perceptions about barriers for women to access cervical cancer screening and early treatment services in Malawi. METHODS: We conducted in-depth interviews with 13 district coordinators and 40 service providers of cervical cancer screening and early treatment services in 13 districts in Malawi. The study was conducted in 2012. The district coordinators helped the research team identify the health facilities which were providing cervical cancer screening and early treatment services. RESULTS: Almost all informants reported that cervical cancer was a major public health problem in their districts and that prevention efforts for this disease were being implemented. They were aware of the test and treat approach using visual inspection with acetic acid (VIA). They, however, said that the delivery of cervical cancer screening and early treatment services was compromised because of factors such as gross shortage of staff, lack of equipment and supplies, the lack of supportive supervision, and the use of male service providers. Informants added that the lack of awareness about the disease among community members, long distances to health facilities, the lack of involvement of husbands, and prevailing misperceptions about the disease (eg, that it is caused by the exposure to the VIA process) affect the uptake of these services. CONCLUSION: While progress has been made in the provision of cervical cancer screening and early treatment services in Malawi, a number of factors affect service delivery and uptake. There is a need to continue creating awareness among community members including husbands and also addressing identified barriers such as shortage of staff and supplies in order to improve uptake of services.

Pilot study of home-based delivery of HIV testing and counseling and contraceptive services to couples in Malawi.

BACKGROUND: HIV counseling and testing for couples is an important component of HIV prevention strategies, particularly in Sub Saharan Africa. The purpose of this pilot study is to estimate the uptake of couple HIV counseling and testing (CHCT) and couple family planning (CFP) services in a single home visit in peri-urban Malawi and to assess related factors. METHODS: This study involved offering CHCT and CFP services to couples in their homes; 180 couples were sampled from households in a peri-urban area of Blantyre. Baseline data were collected from both partners and follow-up data were collected one week later. A pair of male and female counselors approached each partner separately about HIV testing and counseling and contraceptive services and then, if both consented, CHCT and CFP services (pills, condoms and referrals for other methods) were given. Bivariate and multivariate logistic regression analyses were done to examine the relationship between individual partner characteristics and acceptance of the services. Selected behaviors reported pre- and post-intervention, particularly couple reports on contraceptive use and condom use at last sex, were also tested for differences. RESULTS: 89% of couples accepted at least one of the services (58% CHCT-only, 29% CHCT + CFP, 2% CFP-only). Among women, prior testing experience (p < 0.05), parity (p < 0.01), and emotional closeness to partner (p < 0.01) had significant bivariate associations with acceptance of at least one service. Reported condom use at last sex increased from 6% to 25% among couples receiving any intervention. First-ever HIV testing was delivered to 25 women and 69 men, resulting, respectively, in 4 and 11 newly detected infections. CONCLUSIONS: Home-based CHCT and CFP were very successful in this pilot study with high proportions of previously untested husbands and wives accepting CHCT and there were virtually no negative outcomes within one week. This study supports the need for further research and testing of home- and couple-based approaches to expand access to HCT and contraceptive services to prevent the undesired consequences of sexually transmitted infection and unintended pregnancy via unprotected sex.

What makes staff consider leaving the health service in Malawi?

BACKGROUND: Malawi faces a severe shortage of health workers, a factor that has contributed greatly to high maternal mortality in the country. Most clinical care is performed by mid-level providers (MLPs). While utilization of these cadres in providing health care is a solution to the current shortages, demotivating factors within the Malawian health system are pushing them into private, non-governmental, and other non-health related positions. This study aims to highlight these demotivating factors by exploring the critical aspects that influence MLPs' intention to leave their jobs. METHODS: This descriptive qualitative study formed part of the larger Health Systems Strengthening for Equity (HSSE) study. Data presented in this paper were collected in Malawi using the Critical Incident Analysis tool. Participants were asked to narrate an incident that had happened during the past three months which had made them seriously consider leaving their job. Data were subjected to thematic analysis using NVivo 8 software. RESULTS: Of the 84 respondents who participated in a Critical Incident Analysis interview, 58 respondents (69%) indicated they had experienced a demotivating incident in the previous three months that had made them seriously consider leaving their job. The most commonly cited critical factors were being treated unfairly or with disrespect, lack of recognition of their efforts, delays and inconsistencies in salary payments, lack of transparent processes and criteria for upgrading or promotion, and death of patients. CONCLUSION: Staff motivation and an enabling environment are crucial factors for retaining MLPs in the Malawian health system. This study revealed key 'tipping points' that drive staff to seriously consider leaving their jobs. Many of the factors underlying these critical incidents can be addressed by improved management practices and the introduction of fair and transparent policies. Managers need to be trained and equipped with effective managerial skills and staff should have access to equal opportunities for upgrading and promotion. There is need for continuous effort to mobilize the resources needed to fill gaps in basic equipment, supplies, and medicine, as these are critical in creating an enabling environment for MLPs.

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

BACKGROUND: Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. METHODS: This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/µL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. RESULTS: Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. CONCLUSIONS: Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Clinical and genetic determinants of plasma nevirapine exposure following an intrapartum dose to prevent mother-to-child HIV transmission.

OBJECTIVE: Nevirapine is metabolized by cytochrome P450 (CYP) 2B6 and CYP3A4. We characterized relationships between clinical parameters, human genetics, pharmacokinetics, and human immunodeficiency virus type 1 (HIV-1) drug resistance mutations in pregnant women following single-dose intrapartum nevirapine. METHODS: In AIDS Clinical Trials Group study A5207, women received nevirapine at onset of labor and were randomly assigned to receive lamivudine/zidovudine, emtricitabine/tenofovir, or lopinavir/ritonavir for 7 or 21 days. Plasma nevirapine level was quantified on postpartum day 1 and on weeks 1, 3, and 5. We assayed 214 polymorphisms in CYP2B6 and other genes and evaluated associations with pharmacokinetic parameters, including elimination constant, time to protein-adjusted 50% inhibitory concentration (IC50), and week 5 nevirapine level below the quantification limit. RESULTS: Among 301 women with evaluable pharmacokinetic and genotype data, lower body mass index and random assignment to receive lopinavir/ritonavir were associated with more rapid nevirapine elimination. Among those of African ancestry, longer time to IC50 was associated with CYP2B6 983T → C (P = .004) but not with CYP2B6 516G → T (P = .8). Among Indians, slower nevirapine elimination was associated with CYP2B6 516G → T (P = .04). Emergent resistance was infrequent and not associated with pharmacokinetics or CYP2B6 genotype. CONCLUSIONS: The effects on plasma drug exposure following single-dose nevirapine may be greater for CYP2B6 983T → C than for 516G → T and are less pronounced than at steady state.

Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV.

BACKGROUND: Nevirapine (NVP) resistance emerges in up to 70% of women exposed to single-dose (sd) NVP for prevention of mother-to-child transmission of human immunodeficiency virus (HIV). METHODS: HIV-infected pregnant women were randomized to receive sdNVP and either zidovudine/lamivudine (3TC), tenofovir/emtricitabine (FTC), or lopinavir/ritonavir for either 7 or 21 days. The primary endpoint was the emergence of new NVP resistance mutations as detected by standard population genotype at 2 and 6 weeks after treatment. Low-frequency NVP- or 3TC/FTC-resistant mutants at codons 103, 181, and 184 were sought using allele-specific polymerase chain reaction (ASP). RESULTS: Among 484 women randomized, 422 (87%) received study treatment. Four hundred twelve (98%) women had primary endpoint results available; of these, 5 (1.2%) had new NVP resistance detected by population genotype: 4 of 215 in the 7-day arms (1.9%; K103N in 4 women with Y181C, Y188C, or G190A in 3 of 4) and 1 of 197 (0.5%; V108I) in the 21-day arms (P = .37). Among women with ASP results, new NVP resistance mutations emerged significantly more often in the 7-day arms (13/74 [18%]) than in the 21-day arms (3/66 [5%], P = .019). 3TC/FTC-resistant mutants (M184V/I) emerged infrequently (7/134 [5%]), and their occurrence did not differ by arm. CONCLUSIONS: Three short-term antiretroviral strategies, begun simultaneously with the administration of sdNVP, resulted in a low rate (1.2%) of new NVP-resistance mutations when assessed at 2 and 6 weeks following completion of study treatment by standard genotype. ASP revealed that 21-day regimens were significantly better than 7-day regimens at preventing the emergence of minor NVP resistance variants. Clinical Trials Registration.NCT00099632.

Fertility and pregnancy outcomes among women with obstetric fistula in rural Malawi.

OBJECTIVE: To assess the fertility and pregnancy experiences of rural Malawian women living with obstetric fistula and following surgical repair of fistula. METHODS: Fertility histories were collected via in-depth interviews with women identified in 2007 as having obstetric fistula and with their family members. RESULTS: Of the 32 affected women interviewed, 17 (53.1%) conceived after developing obstetric fistula: 13 before repair and 6 after repair (with 2 conceiving both pre- and post-repair). Complaints of infertility were more frequent and urgent among women who had undergone repair than among those who had not. Over half (53.8%) of the women who conceived while living with obstetric fistula and all of those who conceived post-repair experienced at least 1 spontaneous abortion or perinatal death. Nineteen (47.5%) of the 40 pregnancies among women living with obstetric fistula and 7 (70.0%) of the 10 pregnancies among women post-repair ended in spontaneous abortion or perinatal death. CONCLUSION: Even 2 years after undergoing surgical repair, women can continue to experience the effects of obstetric fistula, which include infertility, spontaneous abortion, and perinatal mortality. The factors responsible for extensive infertility and poor pregnancy outcome in women post-repair warrant further investigation.