Prevention of mother-to-child transmission of HIV-1 by antiretroviral treatment and the impact on maternal health in Dar es Salaam, Tanzania

This thesis describes the results of the Mitra Plus study, including the outcome of antiretroviral therapy (ART) for preventing mother-to-child transmission (PMTCT) of HIV-1 in breastfeeding women and improving HIV- free survival (Paper I), treatment outcome of women initiated on ART for life (Paper II) and reasons for poor drug adherence (Paper III) in Dar es Salaam, Tanzania. Another study (qualitative in nature) explored women’s preferred treatment option for the prevention of breast milk transmission of HIV (Paper IV). In the Mitra Plus study, 501 HIV-1 infected pregnant women were treated with Zidovudine + Lamivudine + Nevirapine /Nelfinavir from 34 weeks of gestation. Treatment of mothers was stopped at six months post-delivery except for those who needed ART for their own health (CD4 cell count = 200/µL or WHO stage III or IV). Mothers were advised to exclusively breastfeed and to wean abruptly when the infant was between five and six months. The cumulative HIV-1 rates determined by Kaplan Meier survival analysis of transmission of 441 infants were 4.1% (95% confidence intervals (CI) 2.2-6.0%) at six weeks, 5.0% (95% CI 2.9-7.1%) at six months and 6.0% (95% CI 3.7-8.3%) at 18 months post-delivery. The cumulative risk of HIV transmission between six weeks and six months was 1.0% and between six months and 18 months was 1.1%. The cumulative HIV infection or death rate was 13.6% (95% CI 10.3-16.9%) at 18 months after delivery. Thus extended maternal prophylaxis with ART resulted in low HIV-1 transmission during breastfeeding and a high HIV-free child survival at 18 months. Follow-up of the Mitra Plus women on ART for life revealed that, following an initial treatment success at three and six months, virologic and immunologic failure were common at 12 and 24 months postpartum. A high proportion of viremic mothers also had drug resistance mutations. The mortality rate was fairly low, 5.9% (95% CI 2.5-13.7%). The probability of virologic and immunologic failure was associated with reported non-perfect adherence to ART at month 24 postpartum. In-depth interviews revealed that women’s main motivation for ART adherence was to protect the infant from HIV infection. HIV-related stigma, poverty and overwhelming daily demands were other important barriers to ART adherence. Among the currently recommended WHO Options for preventing breast milk transmission (Ainfant prophylaxis, B- maternal prophylaxis and B+- maternal treatment for life) women preferred Option B as they thought it was better than Option A because of less risk for HIVassociated stigma, less drug side effects for the child and better logistics for postnatal adherence. Women were not in favour of Option B+ as they anticipated loss of motivation after protecting the child, fearing drug side effects and many did not feel ready to embark on lifelong medication when asymptomatic regardless of CD4 count. In conclusion, women should be counselled about the possibility to “opt-out” of ART after cessation of breastfeeding. Drug adherence counselling, drug safety and benefits, economic concerns and available resources for laboratory monitoring and evaluation should be addressed during B+ implementation to enhance long-term feasibility and effectiveness

Predictors of low birth weight and 24-hour perinatal outcomes at Muhimbili National Hospital in Dar es Salaam, Tanzania: a five-year retrospective analysis of obstetric records

Introduction: The global prevalence of low birth weight (LBW) is 16%, representing more than 20 million infants worldwide, of which 96% are born in low-income countries. This study aimed to determine the prevalence, predictors and perinatal outcomes of LBW newborns. Methods: We conducted a retrospective analysis of data obtained from the hospital\u27s obstetric and neonatal database. Descriptive statistics and multivariate logistic regression were performed with 95% confidence intervals (CI). Results: The prevalence of LBW was 21% (n = 8,011) and two-thirds of these were delivered at term. Seven percent of newborns were stillbirths and 2% died within 24hrs after birth. Logistic regression revealed that primigravida and grand multiparity were associated with LBW (OR: 1.25, 95%CI: 1.15-1.37; and OR: 1.21, 95%CI: 1.01-1.25, respectively). Having(ANC) visits was associated with increased odds of LBW (OR: 1.74, 95%CI: 1.59-1.87). Regression models revealed an independent association between LBW and increased odds of stillbirths (OR = 7.20, 95%CI 6.71-7.90), low Apgar score (OR = 3.42, 95%CI: 3.12- 3.76) and early neonatal deaths (OR = 1.82, 95%CI: 1.51-2.19). Conclusion: The prevalence of LBW was high and was associated with extreme maternal age groups, grand multiparity, low maternal education, low number of ANC visits and obstetrics risks factors and complications. Both LBW and prematurity were independently associated with poor perinatal outcome. Future interventions should focus on improving the quality of ANC and integrating peripartum emergency obstetric and neonatal care

‘Essential but not always available when needed’ – an interview study of physicians’ experiences and views regarding use of obstetric ultrasound in Tanzania

Background The value of obstetric ultrasound in high-income countries has been extensively explored but evidence is still lacking regarding the role of obstetric ultrasound in low-income countries. Objective We aimed to explore experiences and views among physicians working in obstetric care in Tanzania, on the role of obstetric ultrasound in relation to clinical management. Design A qualitative study design was applied. Data were collected in 2015, through 16 individual interviews with physicians practicing in obstetric care at hospitals in an urban setting in Tanzania. Data were analyzed using qualitative content analysis. Results Use of obstetric ultrasound in the management of complicated pregnancy was much appreciated by participating physicians, although they expressed considerable concern about the lack of ultrasound equipment and staff able to conduct the examinations. These limitations were recognized as restricting physicians’ ability to manage complications adequately during pregnancy and birth. Better availability of ultrasound was requested to improve obstetric management. Concerns were also raised regarding pregnant women\u27s lack of knowledge and understanding of medical issues which could make counseling in relation to obstetric ultrasound difficult. Although the physicians perceived a positive attitude toward ultrasound among most pregnant women, occasionally they came across women who feared that ultrasound might harm the fetus. Conclusions There seems to be a need to provide more physicians in antenatal care in Tanzania with ultrasound training to enable them to conduct obstetric ultrasound examinations and interpret the results themselves. Physicians also need to acquire adequate counseling skills as counseling can be especially challenging in this setting where many expectant parents have low levels of education. Providers of obstetric care and policy makers in Tanzania will need to take measures to ensure appropriate use of the scarce resources in the Tanzanian health care system and prevent the potential risk of overuse of ultrasound in pregnancy

Breast Milk from Tanzanian Women has Divergent Effects on Cell-Free and Cell-Associated HIV-1 Infection in Vitro.

Transmission of HIV-1 during breastfeeding is a significant source of new pediatric infections in sub-Saharan Africa. Breast milk from HIV-positive mothers contains both cell-free and cell-associated virus; however, the impact of breast milk on HIV-1 infectivity remains poorly understood. In the present study, breast milk was collected from HIV-positive and HIV-negative Tanzanian women attending antenatal clinics in Dar es Salaam. Milk was analyzed for activity in vitro against both cell-free and cell-associated HIV-1. Potent inhibition of cell-free R5 and X4 HIV-1 occurred in the presence of milk from all donors regardless of HIV-1 serostatus. Inhibition of cell-free HIV-1 infection positively correlated with milk levels of sialyl-Lewis(X) from HIV-positive donors. In contrast, milk from 8 of 16 subjects enhanced infection with cell-associated HIV-1 regardless of donor serostatus. Milk from two of these subjects contained high levels of multiple pro-inflammatory cytokines including TNFα, IL-1β, IL-6, IL-8, MIP-1α, MIP-1β, MCP-1 and IP-10, and enhanced cell-associated HIV-1 infection at dilutions as high as 1∶500. These findings indicate that breast milk contains innate factors with divergent activity against cell-free and cell-associated HIV-1 in vitro. Enhancement of cell-associated HIV-1 infection by breast milk may be associated with inflammatory conditions in the mother and may contribute to infant infection during breastfeeding

Fetal to Neonatal Heart Rate Transition during Normal Vaginal Deliveries: A Prospective Observational Study

Documentation of fetal to neonatal heart rate (HR) transition is limited. The aim of the current study was to describe HR changes from one hour before to one hour after normal vaginal deliveries. We conducted a prospective observational cohort study in Tanzania from 1 October 2020 to 30 August 2021, including normal vaginal deliveries with normal neonatal outcomes. HR was continuously recorded from one hour before to one hour after delivery, using the Moyo fetal HR meter, NeoBeat newborn HR meter, and the Liveborn Application for data storage. The median, 25th, and 75th HR percentiles were constructed. Overall, 305 deliveries were included. Median (interquartile range; IQR) gestational age was 39 (38–40) weeks and birthweight was 3200 (3000–3500) grams. HR decreased slightly during the last 60 min before delivery from 136 (123,145) to 132 (112,143) beats/minute. After delivery, HR increased within one minute to 168 (143,183) beats/min, before decreasing to around 136 (127,149) beats/min at 60 min after delivery. The drop in HR in the last hour of delivery reflects strong contractions and pushing. The rapid increase in initial neonatal HR reflects an effort to establish spontaneous breathing.publishedVersio

Virologic and Immunologic Failure, Drug Resistance and Mortality during the First 24 Months Postpartum among HIV-Infected Women Initiated on Antiretroviral Therapy for Life in the Mitra plus Study, Dar es Salaam, Tanzania.

In the Mitra plus study of prevention of mother-to-child transmission of HIV-1, which included 501 women in Dar es Salaam, Tanzania, triple antiretroviral therapy (ART) was given from late pregnancy throughout breastfeeding up to 6 months postnatally. Here we report findings in a sub-cohort of women with ≤200 CD4cells/μL at enrolment who were continued on ART for life and followed up during 24 months after delivery to determine virologic and immunologic responses, drug resistance and mortality. Blood samples for viral load and CD4 counts testing were collected at enrolment and at 3, 6, 12 and 24 months postpartum. HIV drug resistance testing was performed at 12 months. Data analysis included descriptive statistics and multivariate analysis using Generalized Estimated Equations of 73 women with at least two postpartum assessments. The mortality analysis included 84 women who had delivered. The proportion of women with a viral load≥400 copies/mL was 97% (71/73) at enrolment, 16% (11/67), 22% (15/69), 61% (36/59) and 86% (48/56) at 3, 6, 12 and 24 months postpartum, respectively. The proportion of women with immunologic failure was 12% (8/69), 25% (15/60) and 41% (24/58) at 6, 12 and 24 months, respectively. At 12 months, drug resistance was demonstrated in 34% (20/59), including 12 with dual-class resistance. Self-report on drug adherence was 95% (64/68), 85% (56/66), 74% (39/53) and 65% (30/46) at 3, 6, 12 and 24 months, respectively. The mortality rate was 5.9% (95% CI 2.5-13.7%) at 24 months. The probability of virologic and immunologic failure was significantly higher among women who reported non-perfect adherence to ART at month 24 postpartum. Following an initial decline of viral load, virologic failure was common at 12 and 24 months postpartum among women initiated on ART for life during pregnancy because of low CD4 cell counts. A high proportion of viremic mothers also had resistance mutations. However, at 24 months follow-up, the mortality rate was still fairly low. Continuous adherence counseling and affordable means of monitoring of the virologic response are crucial for successful implementation of the WHO Option B+ guidelines to start all HIV-infected pregnant women on ART for life

Implementation of a novel continuous fetal Doppler (Moyo) improves quality of intrapartum fetal heart rate monitoring in a resource-limited tertiary hospital in Tanzania: An observational study

Background Intrapartum Fetal Heart Rate (FHR) monitoring is crucial for the early detection of abnormal FHR, facilitating timely obstetric interventions and thus the potential reduction of adverse perinatal outcomes. We explored midwifery practices of intrapartum FHR monitoring pre and post implementation of a novel continuous automatic Doppler device (the Moyo). Methodology A pre/post observational study among low-risk pregnancies at a tertiary hospital was conducted from March to December 2016. In the pre-implementation period, intermittent monitoring was conducted with a Pinard stethoscope (March to June 2016, n = 1640 women). In the post-implementation period, Moyo was used for continuous FHR monitoring (July-December 2016, n = 2442 women). The primary outcome was detection of abnormal FHR defined as absent, FHR160bpm. The secondary outcomes were rates of assessment/documentation of FHR, obstetric time intervals and intrauterine resuscitations. Chi-square test, Fishers exact test, t-test and Mann-Whitney U test were used in bivariate analysis whereas binary and multinomial logistic regression were used for multivariate. Results Moyo use was associated with greater detection of abnormal FHR (8.0%) compared with Pinard (1.6%) (p Conclusion Implementation of the Moyo device, which continuously measures FHR, was associated with improved quality in FHR monitoring practices and the detection of abnormal FHR. These improvements led to more frequent and timely obstetric responses. Follow-up studies in a high-risk population focused on a more targeted description of the FHR abnormalities and the impact of intrauterine resuscitation is a critical next step in determining the effect on reducing perinatal mortality

Health professionals\u27 experiences and views on obstetric ultrasound in Vietnam: a regional, cross-sectional study

Objectives: Obstetric ultrasound is an important part of antenatal care in Vietnam, although there are great differences in access to antenatal care and ultrasound services across the country. The aim of this study was to explore Vietnamese health professionals\u27 experiences and views of obstetric ultrasound in relation to clinical management, resources and skills. Design: A cross-sectional questionnaire study was performed as part of the CROss Country UltraSound study. Setting: Health facilities (n=29) in urban, semiurban and rural areas of Hanoi region in Vietnam. Participants: Participants were 289 obstetricians/gynaecologists and 535 midwives. Results: A majority (88%) of participants agreed that \u27every woman should undergo ultrasound examination\u27 during pregnancy to determine gestational age. Participants reported an average of six ultrasound examinations as medically indicated during an uncomplicated pregnancy. Access to ultrasound at participants\u27 workplaces was reported as always available regardless of health facility level. Most participants performing ultrasound reported high-level skills for fetal heart rate examination (70%), whereas few (23%) reported being skilled in examination of the anatomy of the fetal heart. Insufficient ultrasound training leading to suboptimal pregnancy management was reported by 37% of all participants. \u27Better quality of ultrasound machines\u27, \u27more physicians trained in ultrasound\u27 and \u27more training for health professionals currently performing ultrasound\u27 were reported as ways to improve the utilisation of ultrasound. Conclusions: Obstetric ultrasound is used as an integral part of antenatal care at all selected health facility levels in the region of Hanoi, and access was reported as high. However, reports of insufficient ultrasound training resulting in suboptimal pregnancy management indicate a need for additional training of ultrasound operators to improve utilisation of ultrasound

Maternal health care professionals’ experiences and views on the use of obstetric ultrasound in Rwanda: A cross-sectional study

Background This study, undertaken in Rwanda, aimed to investigate health professionals’ experiences and views on the following topics: current clinical guidelines for ultrasound from second trimester at the clinic, regional and national levels, and adherence to clinical guidelines; medically indicated ultrasound examinations; non-medical use of ultrasound including ultrasounds on maternal request; commercialisation of ultrasound; the value of ultrasound in relation to other clinical examinations in pregnancy; and ultrasound and medicalisation of pregnancy. Methods A cross-sectional design was adopted. Health professionals providing antenatal care and delivery services to pregnant women in 108 health facilities were invited to complete a survey, which was developed based on the results of earlier qualitative studies undertaken as part of the CROss Country Ultrasound Study (CROCUS). Results Nine hundred and seven health professionals participated: obstetricians/gynecologists (3.2%,) other physicians (24.5%), midwives (29.7%) and nurses (42.7%). Few physicians reported the existence of clinical guidelines at clinic, regional or national levels in Rwanda, and guidelines were moderately adhered to. Three obstetric ultrasound examinations were considered medically indicated in an uncomplicated pregnancy. Most participants (73.0%) were positive about obstetric ultrasound examinations on maternal request. Commercialisation was not considered a problem, and the majority (88.5%) agreed that ultrasound had contributed to medicalisation of pregnancy. Conclusions Findings indicate that clinical guidelines for the use of obstetric ultrasound are limited in Rwanda. Non-medically indicated obstetric ultrasound was not considered a current problem at any level of the healthcare system. The positive attitude to obstetric ultrasound examinations on maternal request may contribute to further burden on a maternal health care system with limited resources. It is essential that limited obstetric ultrasound resources are allocated where they are most beneficial, and clearly stated medical indications would likely facilitate this

Women's Preferences Regarding Infant or Maternal Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission of HIV during Breastfeeding and Their Views on Option B+ in Dar es Salaam, Tanzania.

The WHO 2010 guidelines for prevention of mother-to-child transmission (PMTCT) of HIV recommended prophylactic antiretroviral treatment (ART) either for infants (Option A) or mothers (Option B) during breastfeeding for pregnant women with a CD4 count of >350 cell/µL in low-income countries. In 2012, WHO proposed that all HIV-infected pregnant women should receive triple ART for life (B+) irrespective of CD4 count. Tanzania has recently switched from Option A to B+, with a few centers practicing B. However, more information on the real-life feasibility of these options is needed. This qualitative study explored women's preferences for Option A vs B and their views on Option B+ in Dar es Salaam, Tanzania. We conducted four focus group discussions with a total of 27 pregnant women with unknown HIV status, attending reproductive and child health clinics, and 31 in-depth interviews among HIV-infected pregnant and post-delivery women, 17 of whom were also asked about B+. Most participants were in favor of Option B compared to A. The main reasons for choosing Option B were: HIV-associated stigma, fear of drug side-effects on infants and difficult logistics for postnatal drug adherence. Some of the women asked about B+ favored it as they agreed that they would eventually need ART for their own survival. Some were against B+ anticipating loss of motivation after protecting the child, fearing drug side-effects and not feeling ready to embark on lifelong medication. Some were undecided. Option B was preferred. Since Tanzania has recently adopted Option B+, women with CD4 counts of >350 cell/µL should be counseled about the possibility to "opt-out" from ART after cessation of breastfeeding. Drug safety and benefits, economic concerns and available resources for laboratory monitoring and evaluation should be addressed during B+ implementation to enhance long-term feasibility and effectiveness