Understanding women's engagement in HIV care after initiating antiretroviral therapy during pregnancy in South Africa

Background: Sustained engagement in HIV care, including adherence to antiretroviral therapy (ART) and retention in HIV services, is essential to optimize maternal health and prevent perinatal, postnatal and sexual HIV transmission. However, engagement in care remains a substantial challenge for pregnant and postpartum women. Women’s experience of and response to barriers to engagement in care, including ART side effects, transfer of care and mobility, may be altered by the transitions experienced in pregnancy and motherhood, and there have been few quantitative analyses of these risk factors in maternal ART cohorts. The way engagement in HIV care is measured also varies widely and no gold standard measures of ART adherence or retention exist. Composite assessments of adherence and retention, including drug concentrations, longitudinal self-reported adherence, and interlinked routine electronic health data, have not been thoroughly evaluated among African women living with HIV. To address these gaps in knowledge, this thesis investigates novel measures of ART adherence, and evaluates interlinked routine electronic health data to measure retention in a South African maternal ART cohort. It describes maternal engagement in HIV care, and examines barriers to engagement that require consideration specific to maternal ART. Methods: This research included women who initiated ART during pregnancy in a large integrated antenatal care and ART clinic in Gugulethu, South Africa (2013-2014). Until July 2013, only women who met certain clinical criteria (CD4 cell count 0.850) compared to self-reported adherence using a cross-sectional three-item scale (0.756). Longitudinal measurement of the same self-reported adherence scale showed that reporting worse adherence on any of three items over consecutive visits could predict viremia (>50 and >1000 copies/mL), particularly among women who were suppressed at the initial visit. Measuring retention using routine interlinked electronic data facilitated tracing of women beyond transfer from the integrated clinic to any clinic where they accessed HIV care postpartum. Estimates of retention varied widely using different retention definitions and data sources. Overall, electronic primary health care data, linked across clinics, performed better than laboratory data alone and was a robust measure for monitoring retention in HIV care. Conclusions: Taken together, these findings underscore a concerning level of disengagement from HIV care during and after pregnancy. Potential ART side effects, required transfer of care, the potential challenges of mobility and the importance of sustained engagement in care beyond pregnancy and breastfeeding, should be emphasised in ART counselling. Drug concentrations in DBS and plasma strongly predict viral suppression, but these data on longitudinal self-reported adherence provide a proof of concept for a low resource interim adherence measure that warrants further investigation in routine care settings with limited resources for viral load or drug concentration testing. Transfer of care and postpartum mobility mean that interlinked data sources are essential to obtain accurate estimates of retention postpartum. Further evaluation of the optimal approaches to transferring maternal ART care and the development of interventions to support engagement both in and beyond the clinic of ART initiation will be critical to sustain maternal engagement in HIV care in the long term

Self-reported side effects and adherence to antiretroviral therapy in HIV-infected pregnant women under option B+: a prospective study

BACKGROUND: Antiretroviral therapy (ART) regimens containing efavirenz (EFV) are recommended as part of universal ART for pregnant and breastfeeding women. EFV may have appreciable side effects (SE), and ART adherence in pregnancy is a major concern, but little is known about ART SE and associations with adherence in pregnancy. METHODS: We investigated the distribution of patient-reported SE (based on Division of AIDS categories) and the association of SE with missed ART doses in a cohort of 517 women starting EFV+3TC/FTC+TDF during pregnancy. In analysis, SE were considered in terms of their overall frequency, by systems category, and by latent classes. RESULTS: Overall 97% of women reported experiencing at least one SE after ART initiation, with 48% experiencing more than five SE. Gastrointestinal, central nervous system, systemic and skin SE were reported by 81%, 85%, 79% and 31% of women, respectively, with considerable overlap across groups. At least one missed dose was reported by 32% of women. In multivariable models, ART non-adherence was associated with systemic SE compared to other systems categories, and measures of the overall burden of SE experienced were most strongly associated with missed ART doses. CONCLUSION: These data demonstrate very high levels of SE in pregnant women initiating EFV-based ART and a strong association between SE burden and ART adherence. ART regimens with reduced SE profiles may enhance adherence, and as countries expand universal ART for all adult patients, counseling must include preparation for ART SE

Experiences of HIV-positive postpartum women and health workers involved with community-based antiretroviral therapy adherence clubs in Cape Town, South Africa

Background The rollout of universal, lifelong treatment for all HIV-positive pregnant and breastfeeding women (“Option B+”) has rapidly increased the number of women initiating antiretroviral treatment (ART) and requiring ART care postpartum. In a pilot project in South Africa, eligible postpartum women were offered the choice of referral to the standard of care, a local primary health care clinic, or a community-based model of differentiated ART services, the adherence club (AC). ACs have typically enrolled only non-pregnant and non-postpartum adults; postpartum women had not previously been referred directly from antenatal care. There is little evidence regarding postpartum women’s preferences for and experiences of differentiated models of care, or the capacity of this particular model to cater to their specific needs. This qualitative paper reports on feedback from both postpartum women and health workers who care for them on their respective experiences of the AC. Methods One-on-one in-depth qualitative interviews were conducted with 19 (23%) of the 84 postpartum women who selected the AC and were retained at approximately 12 months postpartum, and 9 health workers who staff the AC. Data were transcribed and thematically analysed using NVivo 11. Results Postpartum women’s inclusion in the AC was acceptable for both participants and health workers. Health workers were welcoming of postpartum women but expressed concerns about prospects for longer term adherence and retention, and raised logistical issues they felt might compromise trust with AC members in general. Conclusions Enrolling postpartum women in mixed groups with the general adult population is feasible and acceptable. Preliminary recommendations are offered and may assist in supporting the specific needs of postpartum women transitioning from antenatal ART care. Trial registration Number NCT02417675 clinicaltrials.gov/ct2/show/record/NCT02417675 (retrospective reg.

Integration of postpartum healthcare services for HIV-infected women and their infants in South Africa: A randomised controlled trial

Background As the number of HIV-infected women initiating lifelong antiretroviral therapy (ART) during pregnancy increases globally, concerns have emerged regarding low levels of retention in HIV services and suboptimal adherence to ART during the postpartum period. We examined the impact of integrating postpartum ART for HIV+ mothers alongside infant follow-up within maternal and child health (MCH) services in Cape Town, South Africa. Methods and findings We conducted a randomised trial among HIV+ postpartum women aged ≥18 years who initiated ART during pregnancy in the local antenatal care clinic and were breastfeeding when screened before 6 weeks postpartum. We compared an integrated postnatal service among mothers and their infants (the MCH-ART intervention) to the local standard of care (control)—immediate postnatal referral of HIV+ women on ART to general adult ART services and their infants to separate routine infant follow-up. Evaluation data were collected through medical records and trial measurement visits scheduled and located separately from healthcare services involved in either arm. The primary trial outcome was a composite endpoint of women’s retention in ART care and viral suppression (VS) (viral load < 50 copies/ml) at 12 months postpartum; secondary outcomes included duration of any and exclusive breastfeeding, mother-to-child HIV transmission, and infant mortality. Between 5 June 2013 and 10 December 2014, a total of 471 mother–infant pairs were enrolled and randomised (mean age, 28.6 years; 18% nulliparous; 57% newly diagnosed with HIV in pregnancy; median duration of ART use at randomisation, 18 weeks). Among 411 women (87%) with primary endpoint data available, 77% of women (n = 155) randomised to the MCH-ART intervention achieved the primary composite outcome of retention in ART services with VS at 12 months postpartum, compared to 56% of women (n = 117) randomised to the control arm (absolute risk difference, 0.21; 95% CI: 0.12–0.30; p < 0.001). The findings for improved retention in care and VS among women in the MCH-ART intervention arm were consistent across subgroups of participants according to demographic and clinical characteristics. The median durations of any breastfeeding and exclusive breastfeeding were longer in women randomised to the intervention versus control arm (6.9 versus 3.0 months, p = 0.006, and 3.0 versus 1.4 months, p < 0.001, respectively). For the infants, overall HIV-free survival through 12 months of age was 97%: mother-to-child HIV transmission was 1.2% overall (n = 4 and n = 1 transmissions in the intervention and control arms, respectively), and infant mortality was 1.9% (n = 6 and n = 3 deaths in the intervention and control arms, respectively), and these outcomes were similar by trial arm. Interpretation of these findings should be qualified by the location of this study in a single urban area as well as the self-reported nature of breastfeeding outcomes. Conclusions In this study, we found that integrating ART services into the MCH platform during the postnatal period was a simple and effective intervention, and this should be considered for improving maternal and child outcomes in the context of HIV

Re-recruiting postpartum women living with HIV into a follow-up study in Cape Town, South Africa

Objective Recruitment and retention present major challenges to longitudinal research in maternal and child health, yet there are few insights into optimal strategies that can be employed in low-resource settings. Following prior participation in a longitudinal study following women living with HIV through pregnancy and breastfeeding in Cape Town, women were re-contacted at least 18 months after the last study contact and were invited to attend an additional follow-up visit. We describe lessons learnt and offer recommendations for a multiphase recruitment approach. Results Using telephone calls, home visits, clinic tracing and Facebook/WhatsApp messages, we located 387 of the 463 eligible women and successfully enrolled 353 (91% of those contacted). Phone calls were the most successful strategy, yielding 67% of enrolments. Over half of the women had changed their contact information since participation in the previous study. We recommend that researchers collect multiple contact details and use several recruitment strategies in parallel from the start of a study. Participants in longitudinal studies may require frequent contact to update contact information, particularly in settings where mobility is common

Re-recruiting postpartum women living with HIV into a follow-up study in Cape Town, South Africa

Abstract Objective Recruitment and retention present major challenges to longitudinal research in maternal and child health, yet there are few insights into optimal strategies that can be employed in low-resource settings. Following prior participation in a longitudinal study following women living with HIV through pregnancy and breastfeeding in Cape Town, women were re-contacted at least 18 months after the last study contact and were invited to attend an additional follow-up visit. We describe lessons learnt and offer recommendations for a multiphase recruitment approach. Results Using telephone calls, home visits, clinic tracing and Facebook/WhatsApp messages, we located 387 of the 463 eligible women and successfully enrolled 353 (91% of those contacted). Phone calls were the most successful strategy, yielding 67% of enrolments. Over half of the women had changed their contact information since participation in the previous study. We recommend that researchers collect multiple contact details and use several recruitment strategies in parallel from the start of a study. Participants in longitudinal studies may require frequent contact to update contact information, particularly in settings where mobility is common

Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional biomarkers of meat and fish intake

Purpose Meat and fish consumption are associated with changes in the risk of chronic diseases. Intake is mainly assessed using self-reporting, as no true quantitative nutritional biomarker is available. The measurement of plasma fatty acids, often used as an alternative, is expensive and time-consuming. As meat and fish differ in their stable isotope ratios, δ13C and δ15N have been proposed as biomarkers. However, they have never been investigated in controlled human dietary intervention studies. Objective In a short-term feeding study, we investigated the suitability of δ13C and δ15N in blood, urine and faeces as biomarkers of meat and fish intake. Methods The dietary intervention study (n = 14) followed a randomised cross-over design with three eight-day dietary periods (meat, fish and half-meat–half-fish). In addition, 4 participants completed a vegetarian control period. At the end of each period, 24-h urine, fasting venous blood and faeces were collected and their δ13C and δ15N analysed. Results There was a significant difference between diets in isotope ratios in faeces and urine samples, but not in blood samples (Kruskal–Wallis test, p < 0.0001). In pairwise comparisons, δ13C and δ15N were significantly higher in urine and faecal samples following a fish diet when compared with all other diets, and significantly lower following a vegetarian diet. There was no significant difference in isotope ratio between meat and half-meat–half-fish diets for blood, urine or faecal samples. Conclusions The results of this study show that urinary and faecal δ13C and δ15N are suitable candidate biomarkers for short-term meat and fish intake

CareConekta: study protocol for a randomized controlled trial of a mobile health intervention to improve engagement in postpartum HIV care in South Africa

Abstract Background South Africa is home to the world’s largest antiretroviral therapy program but sustaining engagement along the HIV care continuum has proven challenging in the country and throughout the wider region. Population mobility is common in South Africa, but there are important research gaps in describing this mobility and its impact on engagement in HIV care. Postpartum women and their infants in South Africa are known to be at high risk of dropping out of HIV care after delivery and are frequently mobile. Methods In 2017, we developed a beta version of a smartphone application (app) - CareConekta - that detects a user’s smartphone location to allow for prospective characterization of mobility. Now we will adapt and test CareConekta to conduct essential formative work on mobility and evaluate an intervention - the CareConekta app plus text notifications and phone calls and/or WhatsApp messages - to facilitate engagement in HIV care during times of mobility. During the 3-year project period, our first objective is to evaluate the feasibility, acceptability, and initial efficacy of using CareConekta as an intervention to improve engagement in HIV care. Our second objective is to characterize mobility among South African women during the peripartum period and its impact on engagement in HIV care. We will enroll 200 eligible pregnant women living with HIV and receiving care at the Gugulethu Midwife Obstetric Unit in Cape Town, South Africa. Discussion This work will provide critical information about mobility during the peripartum period and the impact on engagement in HIV care. Simultaneously, we will pilot test an intervention to improve engagement with rigorously assessed outcomes. If successful, CareConekta offers tremendous potential as a research and service tool that can be adapted and evaluated in multiple geographic regions, study contexts, and patient populations. Trial registration ClinicalTrials.gov: NCT03836625. Registered on 8 February 2019

Community-based adherence clubs for postpartum women on antiretroviral therapy (ART) in Cape Town, South Africa: a pilot study

Background With an increasing number of countries implementing Option B+ guidelines of lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women, there is urgent need to identify effective approaches for retaining this growing and highly vulnerable population in ART care. Methods Newly postpartum, breastfeeding women who initiated ART in pregnancy and met eligibility criteria were enrolled, and offered the choice of two options for postpartum ART care: (i) referral to existing network of community-based adherence clubs or (ii) referral to local primary health care clinic (PHC). Women were followed at study measurement visits conducted separately from either service. Primary outcome was a composite endpoint of retention in ART services and viral suppression [VS < 50 copies/mL based on viral load (VL) testing at measurement visits] at 12 months postpartum. Outcomes were compared across postpartum services using chi-square, Fisher’s exact tests and Poisson regression models. The primary outcome was compared across services where women were receiving care at 12 months postpartum in exploratory analyses. Results Between February and September 2015, 129 women (median age: 28.9 years; median time postpartum: 10 days) were enrolled with 65% opting to receive postpartum HIV care through an adherence club. Among 110 women retained at study measurement visits, 91 (83%) achieved the composite endpoint, with no difference between those who originally chose clubs versus those who chose PHC services. Movement from an adherence club to PHC services was common: 31% of women who originally chose clubs and were engaged in care at 12 months postpartum were attending a PHC service. Further, levels of VS differed significantly by where women were accessing ART care at 12 months postpartum, regardless of initial choice: 98% of women receiving care in an adherence club and 76% receiving care at PHC had VS < 50 copies/mL at 12 months postpartum (p = 0.001). Conclusion This study found comparable outcomes related to retention and VS at 12 months postpartum between women choosing adherence clubs and those choosing PHC. However, movement between postpartum services among those who originally chose adherence clubs was common, with poorer VS outcomes among women leaving clubs and returning to PHC services. Trial registration ClinicalTrials.gov NCT02417675 , April 16, 2015 (retrospectively registered)

The Role of Schools in Early Adolescents’ Mental Health: Findings from the MYRIAD Study

This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this recordData Sharing: The corresponding study protocol can be found at https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-1917-4. R code is available from the Open Science Framework (https://osf.io/s63fm/?view_only=5ae58f6c053c4a16b5ddfccd0e6e1ece). The baseline data and codebook from the MYRIAD trial is available from Prof. Kuyken ([email protected]) upon request (release of data is subject to an approved proposal and a signed data access agreement).Objective: Recent studies suggest deteriorating youth mental health. The current UK policy emphasises the role of schools for mental health promotion and prevention, but little data exist on what aspects of schools explain pupils’ mental health. We explored school-level influences on the mental health of young people in a large school-based sample from the UK. Methods: We analysed baseline data from a large cluster randomized controlled trial (ISRCTN 86619085) collected between 2016‒2018 from mainstream UK secondary schools selected to be representative in relation to their quality rating, size, deprivation, mixed or single-sex pupil population and country. Participants were pupils in their first or second year of secondary school. We assessed whether school-level factors were associated with pupil mental health. Results: 26,885 pupils (response rate=90%), aged 11‒14 years, 55% female, attending 85 UK schools, were included. Schools accounted for 2.4% (95% CI=2.0‒2.8; p<0.0001) of the variation in psychopathology, 1.6% (95% CI=1.2‒2.1; p<0.0001) of depression and 1.4% (95% CI=1.0‒1.7; p<0.0001) of well-being. Schools in urban locations, with a higher percentage of free school meals and of White British, were associated with poorer pupil mental health. A more positive school climate was associated with better mental health. Conclusion: School-level variables, primarily related to contextual factors, characteristics of their pupil population, and school climate explain a small but significant amount of variability in young people’s mental health. This might be used to identify schools that are in need of more resources to support young people’s mental health.Wellcome TrustNational Institute for Health Research (NIHR)Medical Research Council (MRC