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People living with HIV may move between health facilities: this is called 'transfer', and includes up- and down-referral based on clinical condition and lateral transfer (e.g. between primary healthcare [PHC] facilities for reasons such as geographic mobility or stigma). Transfers involving PHC facilities occur frequently and are associated with viraemia and disengagement. We reviewed the South African National Department of Health (NDOH) and Southern African HIV Clinicians Society websites and contacted NDOH officials to identify national guidelines applicable to HIV care in South Africa for recommendations on transfers involving PHC facilities. In total, 21/24 (88%) documents mentioned transfer, using the terms 'referral', 'linkage', 'transfer', 'transition' and 'handover'. Guidelines defined 'linkage to care' as connecting individuals to care after HIV testing, but other terms were not well defined. Documents emphasised transfers between different levels of the health system, and transfers between PHC facilities received limited attention. The transfer process was delineated for linkage to care, up- and down-referrals, but not for transfers between PHC facilities. Clinical management of patients transferring between PHC facilities and tracing of patients who requested transfers and missed their visits were not specified. Overall, transfers between PHC facilities were not well addressed and require attention to improve HIV treatment outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: There is growing recognition of obstetric violence in health facilities across the globe. With nearly one in three pregnant women living with HIV in South Africa, it is important to consider the influence of HIV status on birth experiences, including potential experience of obstetric violence as defined by the Respectful Maternity Care Charter. This qualitative analysis aims to understand the factors that shape birth experiences of women living with HIV, including experiences at the nexus of HIV status and obstetric violence, and how women react to these factors., Methods: Data were collected in a Midwife Obstetric Unit in Gugulethu, Cape Town, South Africa, through 26 in-depth interviews with women living with HIV at 6-8 weeks postpartum. Interviews included questions about labor and early motherhood, ART adherence, and social contexts. We combined template style thematic analysis and matrix analysis to refine themes and subthemes., Results: Participants described a range of social and structural factors they felt influenced their birth experiences, including lack of resources and institutional policies. While some participants described positive interactions with healthcare providers, several described instances of obstetric violence, including being ignored and denied care. Nearly all participants, even those who described instances of obstetric violence, described themselves as strong and independent during their birth experiences. Participants reacted to birth experiences by shifting their family planning intentions, forming attitudes toward the health facility, and taking responsibility for their own and their babies' safety during birth., Conclusions: Narratives of negative birth experiences among some women living with HIV reveal a constellation of factors that produce obstetric violence, reflective of social hierarchies and networks of power relations. Participant accounts indicate the need for future research explicitly examining how structural vulnerability shapes birth experiences for women living with HIV in South Africa. These birth stories should also guide future intervention and advocacy work, sparking initiatives to advance compassionate maternity care across health facilities in South Africa, with relevance for other comparable settings., (© 2024. The Author(s).)

Background: Few data exist on myocardial fibrosis and inflammation in youth with HIV., Methods: We performed cardiovascular magnetic resonance (CMR) on a cross section of South African youth: youth with perinatally acquired HIV (YPHIV) undergoing antiretroviral therapy (ART), youth with nonperinatally acquired HIV (YNPHIV) receiving ART, and youth without HIV. Quantile regression models were fit to assess the association between HIV status and CMR outcomes: subclinical fibrosis (late gadolinium enhancement [LGE] mass and fraction, native T1, extracellular volume) and inflammation (native T1, T2 mapping)., Results: Of 464 youth, 287 were YPHIV, 87 were YNPHIV, and 90 were HIV seronegative. The median age was 16 years (range, 11-24). LGE mass was higher in YPHIV and YNPHIV than in youth who were HIV seronegative (1.85 vs 2.00 vs 1.41 g, respectively), as was fraction (5.8% vs 6.4% vs 4.5%); native T1 was highest in YNPHIV. In adjusted analyses, when compared with youth with HIV seronegativity, YPHIV and YNPHIV exhibited higher LGE mass (β = 0.468, P = .001; β = 0.544, P = .002) and LGE fraction (β = 1.587, P < .001; β = 1.781, P < .001). CMR outcomes were similar between YPHIV and YNPHIV., Conclusions: Despite ART use, YPHIV and YNPHIV appear to have higher subclinical myocardial fibrosis than youth who are HIV seronegative and healthy adults in South Africa and may benefit from early screening/monitoring for cardiovascular disease., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We investigated the impact of Drug-Drug Interactions (DDIs) on virologic control among HIV-positive pregnant women initiating antiretroviral therapy while identifying drivers for Traditional Medicine (TM) use and exploring the nature and extent of TM-related DDIs., Methods: Employing a three-pronged approach, we examined DDIs arising from comedication, including TM, in ART. The DolPHIN-2 trial (NCT03249181) randomized 268 HIV-positive pregnant women in Uganda and South Africa to dolutegravir (DTG)-based (135) or efavirenz-based (133) regimens while systematically recording comedications and screening for DDIs. We used Cox regression models to compare time-to-virologic control between participants with and without DDIs. We conducted in-depth interviews and focus group discussions among 37 and 67 women with and without HIV, respectively, to explore reasons for TM use during pregnancy. Additionally, in-vitro and in-vivo studies evaluated the composition and impact of clay-based TM, mumbwa, on DTG plasma exposure., Results: The baseline prevalence of DDIs was 67.2%, with TM use prevalent in 34% of participants, with mumbwa being the most frequent (76%, 69/91). There was no difference in virologic response between participants with and without DDIs. Fetal health and cultural norms were among the reasons cited for TM use. Analysis of mumbwa rods confirmed significant amounts of aluminium (8.4%-13.9%) and iron (4%-6%). In Balb-C mice, coadministration of mumbwa led to a reduction in DTG exposure observed in the AUC0-24 (-21%; P = 0.0271) and C24 (-53%; P = 0.0028)., Conclusions: The widespread use of clay-based TM may compromise HIV treatment, necessitating medication screening and counselling to manage DDIs in pregnant women., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Dolutegravir (DTG)-based antiretroviral therapy is the World Health Organization's preferred first-line regimen for all persons with HIV, including pregnant women. While DTG has been implicated as an obesogen associated with greater weight gain compared to other antiretrovirals, there is a paucity of data in pregnant women and their children. The Obesogenic oRigins of maternal and Child metabolic health Involving Dolutegravir (ORCHID) study is investigating associations between DTG, weight gain, and metabolic outcomes in the context of HIV., Materials & Methods: ORCHID is a prospective observational study taking place in Cape Town, South Africa (NCT04991402). A total of 1920 pregnant women with and without HIV infection are being followed from ≤18 weeks gestational age to 24 months postpartum with their children. Participants attend eleven study visits: 3 antenatal, delivery, and 7 postnatal visits. Several embedded sub-studies address specific scientific aims. Primary outcome measurements in mothers include anthropometry, blood pressure, body composition, dysglycemia, insulin resistance (IR), and dyslipidemia. Other maternal measures include demographics, resting energy expenditure, viral load, physical activity, dietary intake, hepatic steatosis, and repository specimens. Sub-study measurements include markers of adipose inflammation, gut integrity, and satiety/hunger, subcutaneous adipose tissue morphology and mitochondrial function, and metabolomics. Primary outcome measurements in children include anthropometry, adipose tissue mass, dysglycemia, IR, and dyslipidemia. Other variables include fetal growth, birth outcomes, medical/breastfeeding history, caloric intake, neurodevelopment, and repository specimens. Sub-study measurements include metabolites/lipid subspecies in umbilical cord blood, as well as breast milk composition and DTG exposure., Discussion: ORCHID will play a pivotal role in defining obesogenic mechanisms and clinical consequences of DTG use in pregnancy in women with HIV and their children. It will provide insights into metabolic disease risk reduction in the context of HIV/DTG, identify intervention targets, and inform public health approaches to diminish chronic metabolic co-morbidities for women and children., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abrams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This prospective cohort study investigated the mobility patterns of 200 pregnant and postpartum women living with HIV in South Africa. Participants were enrolled during their third trimester from routine antenatal care near Cape Town, South Africa, and followed for six months postpartum. Quantitative data were collected at enrollment and follow-up. Mobility (self-reported) was common among the participants, despite the brief study period and the concurrent COVID-19 pandemic. While most reported stability in their current residence, 71% had a second main residence, primarily in the Eastern Cape (EC). Participants had a median of two lifetime moves, motivated by work, education, and family life. During the study period, 20% of participants met the study definition of travel (>7 days and >50 km), with trips predominantly to the EC, lasting a median duration of 30 days. Over one-third of participants with other living children reported that these children lived apart from them, with the mother's family being primary caregivers. These findings emphasize the need for targeted interventions to support continuity of care for mobile populations, particularly peripartum women living with HIV. The study contributes valuable insights into mobility dynamics and highlights unique barriers faced by this population, contributing to improved HIV care in resource-limited settings.

Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.53 (0.13, 0.92)] and maximum indexed left atrium volume (LAVi) [adjusted z-score: 0.55 (0.08, 1.02)]. In contrast, APHIV with delayed ART had greater indexed LV end-diastolic volume (LVEDVi) [adjusted z-score: 0.47 (0.09, 0.86)] and extracellular volume fraction [adjusted z-score: 0.79 (0.20, 1.37)], but lower GCS [adjusted z-score: -0.51 (-0.91, -0.10)] than HIV-uninfected peers. APHIV had distinct albeit subclinical cardiac phenotypes depending on ART initiation age. Changes in early ART suggested comparatively worse diastology with preserved systolic function while delayed ART was associated with comparatively increased diffuse fibrosis and LV dilatation with reduced systolic function. The long-term clinical significance of these changes remains to be determined., (© 2024. The Author(s).)

Introduction: Outside of pregnancy, evidence shows that persons with HIV initiating or switching to dolutegravir (DTG)-based antiretroviral therapy (ART) experience greater weight gain compared to those on other ART classes. However, there are few data on the impact of DTG-based ART on gestational weight gain (GWG) in sub-Saharan Africa where HIV is most common. According to the National Academy of Medicine (NAM), GWG below and above NAM guidelines is associated with adverse birth outcomes. Therefore, the objective of this study was to describe GWG by HIV status and ART regimen, and examine the associations with adverse birth outcomes., Methods: We enrolled pregnant women with HIV (WHIV) and without HIV (≥18 years) in a peri-urban primary healthcare facility in Cape Town, South Africa between 2019 and 2022. GWG was study-measured at 24-28 (baseline) and 33-38 weeks gestation and converted to GWG rate (kg/week) in accordance with NAM guidelines. GWG z-scores were generated using the INTEGROWTH-21 and US standards to account for differing lengths of gestation. Birth outcome data were obtained from medical records. Associations of GWG z-score with adverse birth outcomes were assessed using multivariable linear or log-binomial regression., Results: Among 292 participants (48% WHIV), median age was 29 years (IQR, 25-33), median pre-pregnancy body mass index (BMI) was 31 kg/m 2 (IQR, 26-36) and 20% were primiparous at baseline. The median weekly rate of GWG was 0.30 kg/week (IQR, 0.12-0.50), 35% had GWG below NAM standards (59% WHIV) and 48% had GWG above NAM standards (36% WHIV). WHIV gained weight more slowly (0.25 vs. 0.37 kg/week, p<0.01) than women without HIV. Weekly rate of GWG did not differ by ART regimen (DTG-based ART 0.25 vs. efavirenz-based ART 0.27 kg/week, p = 0.80). In multivariable analyses, GWG z-score was positively associated with continuous birth weight (mean difference = 68.53 95% CI 8.96, 128.10) and categorical high birth weight of >4000 g (RR = 2.18 95% CI 1.18, 4.01)., Conclusions: Despite slower GWG among WHIV, nearly half of all women gained weight faster than recommended by the NAM. GWG was positively associated with infant birth weight. Interventions to support healthy GWG in sub-Saharan Africa are urgently needed., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: Both dolutegravir and efavirenz are known to be effective in pregnancy and postpartum to prevent vertical transmission of HIV and to maintain maternal health. Both drugs have also been associated with neuropsychiatric symptoms. To what extent, these symptoms occur in pregnant and postpartum women, however, is not yet known., Methods: This was a secondary analysis of the DolPHIN2 study, a multicentre randomized trial among women presenting late in pregnancy with untreated HIV - who received either a dolutegravir-containing or efavirenz-containing regimen. Longitudinal measures of depression, anxiety and sleep quality were analysed during pregnancy and up to 48 weeks postpartum., Results: Among 268 women, median (IQR) Edinburgh Post Natal Depression Score (EPDS) scores were 8 (3-11) and highest at enrolment. In the dolutegravir and efavirenz arm, respectively, 23.7 and 25.6% had an EPDS score above 9, indicating possible or probable depression. Abnormal Hospital Anxiety Depression scores (HADS) (above 11) were seen at least once during follow-up in 42 of patients (15.7%), although no differences were seen between treatment arms. No association was found between EPDS, suicidality and HADS scores and the assigned regimen ( P  = 0.93, 0.97 and 0.18 respectively). Median (IQR) Pittsburgh Sleep Quality index (PSQI) scores for dolutegravir and efavirenz were 6 (5-7) and 5 (5-6.5), respectively, P  = 0.70., Conclusion: No statistically significant differences were observed between efavirenz-containing or dolutegravir-containing regimens. Rates of depression were high, but decreased over the course of time and confirm the need for psychological support after initial HIV diagnosis in pregnancy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Transfers between health facilities of people living with HIV attending primary health care (PHC) including hospital to PHC facility, PHC facility to hospital and PHC facility to PHC facility transfers occur frequently, affect health service planning, and are associated with disengagement from care and viraemia. Data on transfers among people living with diabetes attending PHC, particularly transfers between PHC facilities, are few. We assessed the transfer incidence rate of people living with diabetes attending PHC, and the association between transfers between PHC facilities and subsequent HbA1c values., Methods: We analysed data on HbA1c tests at public sector facilities in the Western Cape Province (2016-March 2020). Individuals with an HbA1c in 2016-2017 were followed-up for 27 months and included in the analysis if ≥18 years at first included HbA1c, ≥2 HbA1cs during follow-up and ≥1 HbA1c at a PHC facility. A visit interval was the duration between two consecutive HbA1cs. Successive HbA1cs at different facilities of any type indicated any transfer, and HbA1cs at different PHC facilities indicated a transfer between PHC facilities. Mixed effects logistic regression adjusted for sex, age, rural/urban facility attended at the start of the visit interval, disengagement (visit interval >14 months) and a hospital visit during follow-up assessed the association between transfers between PHC facilities and HbA1c >8%., Results: Among 102,813 participants, 22.6% had ≥1 transfer of any type. Including repeat transfers, there were 29,994 transfers (14.4 transfers per 100 person-years, 95% confidence interval [CI] 14.3-14.6). A total of 6996 (30.1%) of those who transferred had a transfer between PHC facilities. Visit intervals with a transfer between PHC facilities were longer (349 days, interquartile range [IQR] 211-503) than those without any transfer (330 days, IQR 182-422). The adjusted relative odds of an HbA1c ≥8% after a transfer between PHC facilities versus no transfer were 1.20 (95% CI 1.05-1.37)., Conclusion: The volume of transfers involving PHC facilities requires consideration when planning services. Individuals who transfer between PHC facilities require additional monitoring and support., (© 2024 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Competing Interests: We declare no competing interests.

Introduction: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception., Methods: We analysed data from people living with HIV (aged 15-49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan-Meier curves and proportional-hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum., Results: Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25-27%) had disengaged from care by 1 year and 34% (95% CI 33-36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70-2.60), restarted (C: aHR 3.32, 95% CI 2.70-4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12-2.74) had increased hazards of postpartum disengagement compared to those on ART (A)., Conclusions: There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care., (© 2024 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: Pregnant and breastfeeding women (PBW) in sub-Saharan Africa have high HIV incidence rates and associated risk of vertical transmission to their infants. Oral preexposure prophylaxis (PrEP) and injectable PrEP (long-acting cabotegravir, or CAB-LA) can potentially reduce this HIV transmission, but population-level impacts are uncertain., Methods: We extended a previously developed model of HIV and PrEP in South Africa to allow for variable PrEP duration and preference in PBW. We considered three potential scenarios for PrEP provision to PBW: oral PrEP only, CAB-LA only, and allowing oral/CAB-LA choice, with uptake and retention assumptions informed by South African data, each compared with a 'base' scenario without PrEP for PBW., Results: Without PrEP for PBW, the model estimates 1.31 million new infections will occur between 2025 and 2035 in South African adults and children, including 100 000 in PBW, 16 800 in infants at/before birth, and 35 200 in children through breastmilk. In the oral PrEP-only scenario, these numbers would reduce by 1.2% (95% CI: 0.7-1.7%), 8.6% (4.8-12.9%), 4.0% (2.1-5.8%), and 5.3% (3.0-8.2%) respectively. In the CAB-LA-only scenario, the corresponding reductions would be 6.1% (2.9-9.6%), 41.2% (19.8-65.0%), 12.6% (6.0-19.4%), and 29.5% (13.9-46.8%), respectively, and in the oral/CAB-LA choice scenario, similar reductions would be achieved [5.6% (3.4-8.0%), 39% (23.4-55.9%), 12.4% (7.4-16.8%) and 27.6% (16.5-39.9%) respectively]., Conclusion: CAB-LA has the potential to be substantially more effective than oral PrEP in preventing HIV acquisition in PBW and vertical transmission, and can also modestly reduce HIV incidence at a population level., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: HIV partner disclosure rates remain low among pregnant women living with HIV in many African countries despite potential benefits for women and their families. Partner disclosure can trigger negative responses like blame, violence, and separation. Women diagnosed with HIV late in pregnancy have limited time to prepare for partner disclosure. We sought to understand challenges around partner disclosure and non-disclosure faced by women diagnosed with HIV late in pregnancy in South Africa and Uganda and to explore pathways to safe partner disclosure., Methods: We conducted in-depth interviews and focus group discussions with pregnant women and lactating mothers living with HIV (n = 109), disaggregated by antenatal care (ANC) initiation before and after 20 weeks of gestation, male partners (n = 87), and health workers (n = 53). All participants were recruited from DolPHIN2 trial sites in Kampala (Uganda) and Gugulethu (South Africa). Topic guides explored barriers to partner disclosure, effects of non-disclosure, strategies for safe disclosure. Using the framework analysis approach, we coded and summarised data based on a socio-ecological model, topic guides, and emerging issues from the data. Data was analysed in NVivo software., Results: Our findings illustrate pregnant women who initiate ANC late experience many difficulties which are compounded by the late HIV diagnosis. Various individual, interpersonal, community, and health system factors complicate partner disclosure among these women. They postpone or decide against partner disclosure mainly for own and baby's safety. Women experience stress and poor mental health because of non-disclosure while demonstrating agency and resilience. We found many similarities and some differences around preferred approaches to safe partner disclosure among female and male participants across countries. Women and male partners preferred healthcare workers to assist with disclosure by identifying the 'right' time to disclose, mentoring women to enhance their confidence and communication skills, and providing professional mediation for partner disclosure and couple testing. Increasing the number of counsellors and training them on safe partner disclosure was deemed necessary for strengthening local health services to improve safe partner disclosure., Conclusion: HIV diagnosis late in pregnancy amplifies existing difficulties among pregnant women. Late ANC initiation is an indicator for the likelihood that a pregnant woman is highly vulnerable and needs safeguarding. Respective health programmes should be prepared to offer women initiating ANC late in pregnancy additional support and referral to complementary programmes to achieve safe partner disclosure and good health., (© 2024. The Author(s).)

Background: Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH., Setting: A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included., Methods: Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks., Results: Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain., Conclusion: These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH., Competing Interests: Conflicts of Interest and Source of Funding: The authors declare that they have no competing interests. The study was funded by the Fogarty International Center of the National Institutes of Health under Award Number D43TW010543-05. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The cardiometabolic impact of HIV infection and treatment with antiretroviral therapy (ART) in pregnancy and the postpartum period remains unclear., Methods: We enrolled pregnant persons with (PHIV) and without HIV in Cape Town, South Africa, who were ≥18 years old at 24-28 weeks' gestation and followed them up to 32 months postpartum. We estimated associations between HIV status and cardiometabolic risk including body mass index (BMI), obesity (BMI ≥30 kg/m 2 ), blood pressure (BP; elevated systolic BP ≥130 and/or diastolic ≥85 mmHg), lipid levels, and metabolic syndrome according to the Joint Interim Statement criteria using multivariable log binomial or linear regression models. Subgroup analyses compared PHIV on efavirenz (EFV)- vs dolutegravir (DTG)-based ART., Results: Among 400 participants (n = 200 without HIV, n = 200 PHIV), 52% had prepregnancy obesity and 9% had elevated BP. Postpartum, 57% were classified with obesity, 31% had elevated BP, and 29% had metabolic syndrome. In multivariable analyses, HIV was associated with a lower BMI prepregnancy but not postpartum; however, mean indices were in the obese range regardless of HIV status. Neither BMI nor obesity prepregnancy or postpartum differed by ART regimen. Among PHIV, participants on DTG had higher levels of elevated BP in pregnancy and postpartum, compared with PHIV on EFV., Conclusions: We observed high levels of obesity, elevated BP, and metabolic syndrome in the perinatal period but few differences by HIV status. Participants on DTG may be more likely to have elevated BP in pregnancy and postpartum. Monitoring of cardiometabolic health for pregnant persons on DTG is warranted., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Pregnant and postpartum women (PPW) in Southern Africa are at increased risk of acquiring HIV and curable sexually transmitted infections (STIs). Oral pre-exposure prophylaxis (PrEP) is safe and effective to use during pregnancy to reduce HIV acquisition and vertical transmission. Point-of-care (POC) STI testing can identify PPW at risk of HIV and facilitate risk-differentiated and person-centred counselling to improve PrEP initiation, persistence and adherence. We evaluated the impact of POC STI testing compared with STI syndromic management on PrEP outcomes among PPW in Cape Town, South Africa., Methods: The STI and PrEP in Pregnancy Study enrolled PPW without HIV and ≤34 weeks pregnant at their regular antenatal care visit with follow-up after 1 month. PPW were randomised to receive POC STI testing or STI syndromic management. PPW randomised to POC STI testing self-collected vaginal swabs for Chlamydia trachomatis, Neisseria gonorhoeae and Trichomonas vaginalis (Cepheid GeneXpert) testing and were offered same-day treatment if diagnosed. We compared PrEP initiation at baseline, PrEP prescription refill at 1 month (persistence) and adherence through tenofovir-diphosphate detection in dried blood spots by randomisation arm. In a secondary analysis, we evaluated the association between an STI diagnosis (positive STI test or reporting STI symptoms) with PrEP outcomes., Results: We enrolled and randomised 268 pregnant women. Twenty-eight per cent of women were diagnosed with ≥1 STI. Overall, 65% of women initiated and 79% persisted on PrEP with no significant differences by randomisation arm. Secondary analysis demonstrated that an STI diagnosis (positive STI test or reporting STI symptoms) was associated with higher PrEP initiation (adjusted relative risk=1.28; 95% CI 1.08 to 1.52), controlling for arm, maternal and gestational age., Conclusions: POC STI testing was not associated with PrEP initiation or persistence relative to syndromic management. However, improving STI diagnosis by supplementing syndromic management with POC STI testing could improve PrEP initiation among PPW., Trial Registration Number: NCT03902418; Clinical Trials.gov; 1 April 2019., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Intimate partner violence (IPV) occurs at alarmingly high rates towards pregnant women in South Africa. Experiences of emotional, physical, and sexual IPV in pregnancy can adversely impact the health and safety of mother and fetus. Furthermore, IPV is associated with increased risk of HIV, exacerbating the public health impact of violence among pregnant women in this HIV endemic setting. In-depth understanding of cultural and contextual drivers of experiences of IPV is a critical precursor to development of interventions effectively addressing this issue among pregnant women in South Africa. The present study examines factors contributing to IPV among pregnant women to identify potential points of intervention. We conducted twenty in-depth interviews with postpartum women who used oral pre-exposure prophylaxis (PrEP) in pregnancy and reported recent experiences of IPV and/or ongoing alcohol use in a township near Cape Town, South Africa that experiences a heavy burden of both HIV and IPV. Interpretive thematic analysis was used. Several patterns of IPV during pregnancy were identified and violence was frequently described as co-occurring with male partner alcohol use. A majority of women referenced oral PrEP as their preferred method for HIV prevention, highlighting the agency and discretion it provided as beneficial attributes for women experiencing IPV. Fear of judgement from peers for remaining with an abusive partner and a lack of clear community messaging around IPV were identified as barriers to disclosure and support-seeking. Addressing the lack of social support received by women experiencing IPV during pregnancy in South Africa is essential to comprehensive IPV programming., (© 2024. The Author(s).)

Background: While several methodologies are available to measure adiposity, few have been validated in sub-Saharan African (SSA) and none in postpartum African women living with HIV (WLHIV). We compared bioelectrical impendence analysis (BIA) and air displacement plethysmography (ADP) against dual x -ray absorptiometry (DXA) in South African women and examined differences by HIV and body mass index (BMI) status., Methods: Lin's concordance correlation coefficient (CCC) test was used to examine fat mass (FM), fat free mass (FFM), and total body fat percent (%BF) difference between BIA vs. DXA, and ADP vs. DXA in women living with HIV ( n = 57) and without HIV ( n = 25). The Bland Altman test was used to assess mean differences and the direction of bias., Results: The median age was 31 years (IQR, 26-35) and months postpartum were 11 (IQR, 7-16), 44% of the women had obesity. Lin's CCC for BIA and ADP vs. DXA were both 0.80 for %BF and 0.97 for FM, and 0.86 and 0.80 for FFM, respectively. Mean differences (DXA-BIA and ADP estimates) were 0.22 ± 4.54% ( p = 0.54) and 3.35 ± 3.27% ( p < 0.01) for %BF, -0.82 ± 3.56 kg ( p = 0.06) and 1.43 ± 2.68 kg ( p = 0.01) for FM, -1.38 ± 3.61 kg (p = 0.01) and - 3.34 ± 2.37 kg ( p < 0.01) for FFM, respectively. BIA overestimated %BF in WLHIV and underestimated it in women with obesity., Conclusion: Body composition measurements using BIA and ADP correlated well with DXA, thereby providing alternative, safe tools for measuring postpartum FM and FFM in SSA women, including WLHIV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Madlala, Myer, Geffen, Meyer, Mendham, Goedecke, Bengtson, Jao and Dugas.)

Background: Point-of-care (POC) lateral flow assays (LFA) to detect tenofovir (TFV) in urine have been developed to measure short-term ART adherence. Limited data exist from people living with HIV in routine care., Methods: Adults on TFV-containing regimens, having a routine viral load (VL) at an HIV clinic in Cape Town, South Africa were enrolled in a cross-sectional study. Patients recalled missed ART doses in the past three and 7 days and urine was tested using a POC TFV LFA. VL on the day was abstracted from medical records., Results: Among 314 participants, 293 (93%) had VL <1000 copies/mL, 20 (6%) had no TFV detected and 24 (8%) reported ≥1 missed dose in the past 3 days. Agreement between VL ≥1000 and undetectable TFV was higher compared to 3-day recall of ≥1 missed dose (Kappa 0.504 vs. 0.163, p = 0.015). The AUC to detect VL ≥1000 was 0.747 (95% CI 0.637-0.856) for undetectable TFV. This was statistically significantly better than for 7-day recall (0.571 95% CI 0.476-0.666, p = 0.040) but not for 3-day recall (0.587 95% CI 0.492-0.681, p = 0.071) of ≥1 missed dose., Conclusion: In this largely virally suppressed cohort, TFV in urine had better agreement with VL than self-reported adherence and was a better predictor of viraemia on two of three self-report measures. Used in combination with VL, the POC urine TFV LFA could flag patients with viraemia in the presence of ART. Further research is needed to understand the potential application in different populations on ART, including pregnant women., (© 2023 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Objective: To compare pregnancy outcomes using self-reported and objective levels of intracellular tenofovir diphosphate (TFV-DP) in pregnant women using preexposure prophylaxis (PrEP)., Design: We enrolled pregnant women >15 years without HIV at first antenatal care visit in an observational cohort study to compare pregnancy outcomes by PrEP use., Methods: Exposure defined as: any PrEP use [tenofovir disoproxil and emtricitabine (TDF/FTC]) prescription + reported taking PrEP], or objectively-measured TFV-DP in dried blood spots in PrEP-using pregnant women. The primary outcome was a composite of pregnancy loss, preterm birth (<37weeks), low birthweight (<2500 g), small for gestational age ([SGA] ≤ tenth percentile), or neonatal death. Multivariable logistic regression models evaluated individual and composite adverse outcomes by self-reported or objectively measured PrEP use adjusting for age, gestational age, gravidity and socio-economic status., Results: Between August 19 and February 23, we followed 1195 pregnant women and ascertained 1145 pregnancy outcomes (96%); 72% ( n  = 826) reported taking PrEP while pregnant, 16% did not take PrEP ( n  = 178), 12% were unconfirmed ( n  = 141). Overall, 94.5% ( n  = 1082) had singleton live births with a median birthweight of 3.2 kg [interquartile range (IQR) = 2.9-3.5], with no difference in pregnancy loss between self-reported PrEP exposed vs. unexposed [4.0 vs. 5.6%; adjusted odds ratio (aOR) = 0.65, 95% confidence interval (CI) = 0.32-1.47]. Composite adverse outcomes did not differ by reported PrEP use (20% for both groups; aOR = 1.07, 95% CI = 0.71-1.63). Comparing objective PrEP use (any TFV-DP vs. no TFV-DP or not on PrEP), adverse outcomes did not differ (aOR = 0.64, 95% CI = 0.39-1.04), nor did other outcomes including preterm birth nor SGA., Conclusions: Pregnancy outcomes did not differ by PrEP exposure (self-reported or objective), suggesting real-world efficacy that TDF/FTC as PrEP is safe in pregnancy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Youth living with perinatally acquired HIV infection (YLPHIV) are at risk of developing atherosclerotic cardiovascular disease., Methods: We determined the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries (CA) and abdominal aorta (AA) risk scores among YLPHIV who are ≥15 years old in Cape Town Adolescent and Antiretroviral Cohort. PDAY score was calculated using non-high-density lipoprotein, high-density lipoprotein cholesterol, hyperglycemia, hypertension, obesity, and smoking; a score ≥1 was considered elevated. HIV viremia was categorized as sustained (SV) = viral load (VL) >50 copies/mL, transient (TV) = mix of VL >50 and ≤50 copies/mL, or sustained-virologic suppression = VL <50 copies/mL throughout the study. Among YLPHIV, logistic models were fit to assess factors associated with elevated PDAY., Results: Overall, 218 YLPHIV [median age 16.8 (interquartile range: 15.9-17.8) years, male 47%] were included. Among YLPHIV, 8% (n = 17) had SV, and 54% (n = 118) had TV. Median antiretroviral therapy (ART) duration was 12 (interquartile range: 8-14) years. Among YLPHIV, 30.3% and 18.4% had elevated PDAY for CA and AA, respectively.Among YLPHIV, SV [adjusted odds ratio (aOR) = 18.4, P < 0.01] and TV (aOR = 2.10, P = 0.04) compared with virologic suppression and ART duration in years (aOR = 1.12, P = 0.03) were associated with elevated CA. Male sex was associated with both elevated CA and AA (aOR = 2.14, P = 0.02, and aOR = 3.43, P = 0.01, respectively) and association of SV with elevated AA (aOR = 3.24, P = 0.09)., Conclusions: A substantial proportion of YLPHIV have PDAY scores reflecting increased aggregate atherosclerotic risk. Among YLPHIV, viremia, lifetime ART duration, and male sex contribute to this risk, highlighting the importance of HIV control and the need to monitor cardiometabolic health., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Transfers between health facilities for postpartum women living with HIV are associated with disengagement from care. In South Africa, women must transfer from integrated antenatal/HIV care to general HIV services post-delivery. Thereafter, women transfer frequently e.g. due to geographic mobility. To explore barriers to transfer, we conducted in-depth interviews >2 years post-delivery in 28 participants in a trial comparing postpartum HIV care at primary health care (PHC) antiretroviral therapy (ART) facilities versus a differentiated service delivery model, the adherence clubs, which are the predominant model implemented in South Africa. Data were thematically analysed using inductive and deductive approaches. Women lacked information including where they could transfer to and transfer processes. Continuity mechanisms were affected when women transferred silently i.e. without informing facilities or obtaining referral letters. Silent transfers often occurred due to poor relationships with healthcare workers and were managed inconsistently. Fear of disclosure to family and community stigma led to transfers from local PHC ART facilities to facilities further away affecting accessibility. Mobility and the postpartum period presented unique challenges requiring specific attention. Information regarding long-term care options and transfer processes, ongoing counselling regarding disclosure and social support, and increased health system flexibility are required.

Introduction: We evaluated associations of HIV and antiretroviral therapy (ART) with birth and maternal outcomes at a province-wide-level in the Western Cape, South Africa, in a recent cohort before dolutegravir-based first-line ART implementation., Methods: This retrospective cohort study included pregnant people delivering in 2018-2019 with data in the Western Cape Provincial Health Data Centre which integrates individual-level data on all public sector patients from multiple electronic platforms using unique identifiers. Adverse birth outcomes (stillbirth, low birth weight (LBW), very LBW (VLBW)) and maternal outcomes (early and late pregnancy-related deaths, early and late hospitalizations) were compared by HIV/ART status and adjusted prevalence ratios (aPRs) calculated using log-binomial regression., Results: Overall 171,960 pregnant people and their singleton newborns were included, 19% (N = 32 015) identified with HIV. Amongst pregnant people with HIV (PPHIV), 60% (N = 19 157) were on ART preconception, 29% (N = 9276) initiated ART during pregnancy and 11% (N = 3582) had no ART. Adjusted for maternal age, multiparity, hypertensive disorders and residential district, stillbirths were higher only for PPHIV not on ART [aPR 1.31 (95%CI 1.04-1.66)] compared to those without HIV. However, LBW and VLBW were higher among all PPHIV, with aPRs of 1.11-1.22 for LBW and 1.14-1.54 for VLBW. Pregnancy-initiated ART was associated with early pregnancy-related death (aPR 3.21; 95%CI 1.55-6.65), and HIV with or without ART was associated with late pregnancy-related death (aPRs 7.89-9.01)., Conclusions: Even in the universal ART era, PPHIV experienced higher rates of LBW and VLBW newborns, and higher late pregnancy-related death regardless of ART status than pregnant people without HIV., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Pregnant women in sub-Saharan Africa have high rates of maternal morbidity. There is interest in the impact of the vaginal microbiome on maternal health, including HIV and sexually transmitted infection (STI) acquisition. We characterized the vaginal microbiota of South African women ≥ 18 years with and without HIV in a longitudinal cohort over two visits during pregnancy and one visit postpartum. At each visit, we obtained HIV testing and self-collected vaginal swabs for point-of-care testing for STIs and microbiota sequencing. We categorized microbial communities and evaluated changes over pregnancy and associations with HIV status and STI diagnosis. Across 242 women (mean age 29, 44% living with HIV, 33% diagnosed with STIs), we identified four main community state types (CSTs): two lactobacillus-dominant CSTs (dominated by Lactobacillus crispatus and Lactobacillus iners respectively) and two diverse, non-lactobacillus-dominant CSTs (one dominated by Gardnerella vaginalis and one by diverse facultative anaerobes). From the first antenatal visit to the third trimester (24-36 weeks gestation), 60% of women in the Gardnerella-dominant CST shifted to lactobacillus-dominant CSTs. From the third trimester to postpartum (mean 17 days post-delivery), 80% of women in lactobacillus-dominant CSTs shifted to non-lactobacillus-dominant CSTs with a large proportion in the facultative anaerobe-dominant CST. Microbial composition differed by STI diagnosis (PERMANOVA R 2 = 0.002, p = 0.004), and women diagnosed with an STI were more likely to be categorized as L. iners-dominant or Gardnerella-dominant CSTs. Overall, we found a shift toward lactobacillus dominance during pregnancy and the emergence of a distinct, highly diverse anaerobe-dominant microbiota profile in the postpartum period., (© 2023. The Author(s).)

Background: HIV has become a manageable chronic condition due to the success and scale-up of antiretroviral therapy (ART). Globally, South Africa has the highest number of people living with HIV (PLHIV) and research evidence indicates that countries with the highest burden of PLHIV have a substantial burden of obesity, hypertension (HPT) and type 2 diabetes (T2D). We sought to summarize the burden of these three common NCDs among PLHIV in South Africa., Methods: In this systematic review, multiple databases were searched for articles reporting on the prevalence of obesity, HPT, and T2D among PLHIV in South Africa published since journal inception until March 2022. A meta-analysis was conducted using random-effects models to obtain pooled prevalence estimates of the three NCDs. Heterogeneity was assessed using X 2 test on Cochran's Q statistic., Results: We included 32 studies, with 19, 22 and 18 studies reporting the prevalence of obesity, HPT, and T2D among PLHIV, respectively. The overall prevalence of obesity, HPT, and T2D was 23.2% [95% CI 17.6; 29.9], 25.5% [95% CI 15.6; 38.7], and 6.1% [95% CI 3.8; 9.7] respectively. The prevalence of obesity was significantly higher among women (P = 0.034) compared to men, however the prevalence of HPT and T2D did not differ by sex. The prevalence of each of the three NCDs did not differ significantly between rural, urban, and peri-urban areas. The prevalence of obesity and T2D was higher in studies conducted between 2013 and 2022 compared to studies conducted between 2000 and 2012, while the prevalence of HPT was higher between 2000 and 2012 compared to between 2013 and 2022., Conclusions: These findings suggest that South Africa is experiencing a syndemic of NCDs among people PLHIV highlighting the need to increase cost-effective interventions and management strategies that involve integrated HIV and NCD care in the South African setting., (© 2023. The Author(s).)

Background: While Option B + has made great strides in eliminating vertical transmission of HIV and improving access to lifelong antiretroviral therapy (ART) for women, the postpartum period remains a risk period for disengagement from HIV care and non-adherence., Methods: Longitudinal qualitative data was collected from 30 women living with HIV in Cape Town, South Africa from pregnancy through 1 year postpartum to examine key barriers and facilitators to HIV treatment adherence across this transition. Participants were also asked about their preferences for behavioral intervention content, format, and scope. The intervention development process was guided by Fernandez et al.'s Intervention Mapping process and was informed by the qualitative data, the wider literature on ART adherence, and Transition Theory., Results: The Womandla Health Intervention is a multicomponent intervention consisting of four individual sessions with a lay health worker and four peer group sessions, which span late pregnancy and early postpartum. These sessions are guided by Transition Theory and utilize motivational interviewing techniques to empower women to ascertain their own individual barriers to HIV care and identify solutions and strategies to overcome these barriers., Conclusions: This intervention will be tested in a small scale RCT. If successful, findings will provide an innovative approach to HIV treatment by capitalizing on the transition into motherhood to bolster self-care behaviors, focusing on ART adherence and also women's overall postpartum health and psychosocial needs., (© 2023. The Author(s).)

In a randomised trial, we found that integrated maternal HIV and infant health services through the end of breastfeeding were significantly associated with the primary outcome of engagement in HIV care and viral suppression at 12 months postpartum, compared to the standard of care. Here, we quantitatively explore potential psychosocial modifiers and mediators of this association. Our findings suggest that the intervention was significantly more effective among women experiencing an unintended pregnancy but did not improve outcomes among women reporting risky alcohol use. Although not statistically significant, our results suggest that the intervention may also be more effective among women experiencing higher levels of poverty and HIV-related stigma. We observed no definitive mediator of the intervention effect, but women allocated to integrated services reported better relationships with their healthcare providers through 12 months postpartum. These findings point to high-risk groups that may benefit the most from integrated care, as well as groups for whom these benefits are hampered and that warrant further attention in intervention development and evaluation., (© 2023. The Author(s).)

Background: Despite the overall reduction in the HIV mother-to-child transmission (MTCT) rate in South Africa, poor adherence and retention in care during breastfeeding contribute to this period being a major driver of MTCT in South Africa. To improve this retention, postnatal clubs were created as an integrated, differentiated model of care providing psychosocial support and comprehensive care for the mother-infant pairs (MIP), including HIV and under-5-child services. We describe the implementation of these facility-based clubs and examine its health outcomes in a peri-urban primary health care setting in Cape Town, South Africa., Methods: In this prospective cohort study, conducted between June 2016 and December 2019, MIPs were recruited into postnatal clubs between 6 weeks and 6 months of age and followed-up until 18 months of age. Outcomes including maternal Viral Load (VL), and children's HIV testing were compared to a historical control group. Children's immunizations and maternal sexual and reproductive health outcomes are also described., Results: During the implementation of the postnatal club study period, 484 MIP were recruited with 84% overall attendance, 95% overall viral load suppression, and 98% overall uptake of HIV infant testing. Compared to historical controls, the club infant rapid test uptake was 1.6 times higher (95% CI: 1.4-1.9) at 9 months and 2.0 times higher at 18 months (95% CI: 1.6-2.6). Through 12 months and between 12-18 months, maternal VL monitoring was higher in the club group compared to the historical control by 1.5 times (95% CI: 1.3-1.6) and 2.6 times (95% CI: 2.1-3.2), respectively, with similar maternal VL suppression. Of 105 infants attending the 12 months visit, 99% were fully vaccinated by one year., Conclusion: MIP in the postnatal clubs showed better PMTCT outcomes than historical controls with high levels of retention in care. Other outcomes such as immunisation results suggest that integration of services, such as in the postnatal club, is feasible and beneficial for MIPs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nelson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We investigated the association between travel and viraemia in post-partum women with human immunodeficiency virus on antiretroviral therapy (ART)., Methods: Data are from a trial of post-partum ART delivery strategies. Women who initiated ART during pregnancy, were clinically stable with a viral load (VL) <400 copies/ml and were <10 weeks post-partum were enrolled at a primary care antenatal clinic in Cape Town, South Africa. Study visits at 3, 6, 12, 18 and 24 months post-partum included questions about travel, defined as ≥1 night spent outside of the city, and VL testing. Generalised mixed effects models assessed the association between travel and subsequent VL ≥400 copies/ml., Results: Among 402 women (mean age 29 y, 35% born in the Western Cape), 69% reported one or more travel events over 24 months. Being born beyond the Western Cape (adjusted odds ratio [aOR] 2.03 [95% confidence interval {CI} 1.49 to 2.77]), duration post-partum in months (aOR 1.03 [95% CI 1.02 to 1.05]) and living with the child (aOR 0.60 [95% CI 0.38 to 0.93]) were associated with travel. In multivariable analyses, a travel event was associated with a 92% increase in the odds of a VL ≥400 copies/ml (aOR 1.92 [95% CI 1.19 to 3.10])., Conclusions: Interventions to support women on ART who travel are urgently required., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Objective: To estimate associations of HIV status and antiretroviral (ART) regimen with gestational diabetes (GDM) and postpartum glucose metabolism., Design: Prospective cohort study., Methods: We enrolled pregnant persons with HIV (PWH) and without HIV in Cape Town, South Africa who were at least 18 years of age at 24-28 weeks' gestation and followed up to 26 months postpartum. Participants were tested for GDM in pregnancy and for diabetes postpartum using a 75 g 2 h oral glucose tolerance test (OGTT) and diagnosed via WHO criteria. We estimated associations of HIV status and ART regime [efavirenz (EFV) versus dolutegravir (DTG)] with GDM and postpartum impaired glucose metabolism using multivariable log binomial or linear regression models., Results: Among 397 participants [median age 30 (interquartile range (IQR) 25-34; n  = 198 without HIV, n  = 199 PWH], the prevalence of GDM was 6% (9 PWH versus 3% without HIV). In multivariable analyses, PWH were at higher risk of GDM [risk ratio (RR) 3.9, 95% confidence interval (CI) 1.4-10.7] after adjustment for prepregnancy BMI and other confounders. GDM risk did not differ by ART regimen (unadjusted prevalence 8.1% DTG versus 5.6% EFV, adjusted RR 1.1, 95% CI 0.2-6.6). Few participants had diabetes, impaired glucose tolerance (IGT), or impaired fasting glucose postpartum ( n  = 13, 6%) with no differences by HIV or ART status., Conclusion: In a setting of universal GDM testing, PWH had an increased risk of impaired glucose metabolism during pregnancy but not postpartum. Among PWH, GDM risk was similar regardless of EFV or DTG use. Given concerns about DTG and weight gain, diabetes risk should continue to be monitored., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite the close relationship between pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and postpartum weight (PPW), these factors are often studied separately. There are no data characterising longitudinal weight trajectories among pregnant and postpartum women in urban African populations. We examined maternal weight trajectories from pregnancy through to 12 months postpartum, factors associated with higher weight trajectory class membership and associations of weight trajectories with infant growth at 12 months., Methods: Data from 989 women were examined for weight trajectories from first antenatal care visit in pregnancy to 12 months postpartum using latent-class growth models. Baseline factors associated with class membership were assessed using multinomial logistic regression. Of the enrolled women, 613 of their infants were assessed for growth at 12 months. Anthropometry measurements for mothers and infants were conducted by a trained study nurse. Associations between maternal weight trajectory class and infant weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) at 12 months of age were analysed using linear regression., Results: Four distinct classes of maternal weight trajectories were identified. The classes included consistent low (29%), consistent medium (37%), medium-high (24%) and consistent high (10%) trajectories. Similar to trends observed with medium-high trajectory, baseline factors positively associated with consistent high class membership included age (OR 1.05, 95% CI 1.01-1.09), pre-pregnancy BMI (OR 2.24, 95% CI 1.97-2.56), stage 1 hypertension (OR 3.28, 95% CI 1.68-6.41), haemoglobin levels (OR 1.39, 95% CI 1.11-1.74) and parity (OR 1.39, 95% CI 1.15-1.67); living with HIV (OR 0.47, 95% CI 0.30-0.74) was inversely associated. In adjusted analyses, compared to consistent medium weight trajectory, consistent low weight trajectory (mean difference -0.41, 95% CI -0.71;-0.12) was associated with decreased, and consistent high weight trajectory (mean difference 1.21, 95% CI 0.59-1.83) with increased infant WAZ at 12 months of age., Conclusion: Identification of unique longitudinal weight trajectory groupings might inform comprehensive efforts targeted at improving healthy maternal weight and infant outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Limited data exist on the differential risk of HIV acquisition between infants born preterm versus those born at term to women living with HIV (WLHIV). With a reported increase in preterm delivery among pregnant WLHIV, understanding the risk of vertical transmission of HIV in preterm infants can inform strategies to optimise the timing of diagnostic testing, antiretroviral prophylaxis, and infant feeding., Objectives: To describe the prevalence and timing of HIV acquisition, in utero versus perinatal, among infants with perinatal HIV exposure born prior to 37 weeks completed gestation age compared to those born at term in the Botswana-based Mpepu study and explore predictors of infant HIV acquisition., Method: Using data extracted from the Mpepu study, we describe the prevalence, timing and risk factors for HIV acquisition in infants born preterm versus those born at term. Fisher exact testing was used to test for differences in prevalence and timing of HIV and a multivariable logistic regression model was used to assess risk factors for infant HIV acquisition., Results: 2866 infants born to WLHIV were included in this secondary analysis. 532 (19%) were born preterm. There was no observed difference in the prevalence of HIV acquisition among infants born preterm versus at term overall (0.8% vs 0.6%, P = 0.54), at birth (0.2% vs 0.3%, P = 1.00) or between 14 and 34 days post-delivery (0.6% vs 0.3%, P = 0.41). The absence of maternal antiretroviral use during pregnancy significantly predicted infant HIV acquisition, with the risk of HIV acquisition reduced by 96% among infants whose mothers were taking antiretroviral treatment (ART) during pregnancy (adjusted odds ratio: 0.003, confidence interval: 0.01-0.02, P < 0.001)., Conclusion: There was no observed increase of in utero and peripartum HIV acquisition among infants born preterm following foetal exposure to HIV compared to those born at term., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)

Introduction: Several HIV-related syndemics have been described among adults. We investigated syndemic vulnerability to hazardous drinking (HD), intimate partner violence (IPV) and household food insecurity (HFIS) in breastfed children born without HIV in urban South Africa. We compared those who were perinatally HIV exposed (CHEU) to those who were not (CHU), under conditions of universal maternal antiretroviral therapy (ART) and breastfeeding., Methods: A prospective cohort of pregnant women living with HIV (WLHIV), and without HIV, were enrolled and followed with their infants for 12 months postpartum (2013-2017). All WLHIV initiated antenatal efavirenz-based ART. Measurements of growth (∼3 monthly), infectious cause hospitalisation, ambulatory childhood illness (2-week recall) and neurodevelopment (BSID-III, measured at ∼12 months' age) were compared across bio-social strata using generalised linear regression models, with interaction terms; maternal data included interview-based measures for HD (AUDIT-C), IPV (WHO VAW) and HFIS., Results: Among 872 breastfeeding mother-infant pairs (n = 461 CHEU, n = 411 CHU), WLHIV (vs. HIV negative) reported more unemployment (279/461, 60% vs. 217/411, 53%; p = 0.02), incomplete secondary education (347/461, 75% vs. 227/411, 55%; p < 0.0001), HD (25%, 117/459 vs. 7%, 30/411; p < 0.0001) and IPV (22%, 101/457 vs. 8%, 32/411; p < 0.0001) at enrolment; and HFIS at 12 months (45%, 172/386 vs. 30%, 105/352; p > 0.0001). There were positive interactions between maternal HIV and other characteristics. Compared to food secure CHU, the mean difference (95% CI) in weight-for-age Z-score (WAZ) was 0.06 (-0.14; 0.25) for food insecure CHU; -0.26 (-0.42; -0.10) for food secure CHEU; and -0.43 (-0.61; -0.25), for food insecure CHEU. Results were similar for underweight (WAZ < -2), infectious-cause hospitalisation, cognitive and motor delay. HIV-IPV interactions were evident for ambulatory diarrhoea and motor delay. There were HIV-HD interactions for odds of underweight, stunting, cognitive and motor delay. Compared to HD-unexposed CHU, the odds ratios (95% CI) of underweight were 2.31 (1.11; 4.82) for HD-exposed CHU; 3.57 (0.84; 15.13) for HD-unexposed CHEU and 6.01 (2.22; 16.22) for HD-exposed CHEU., Conclusions: These data suggest that maternal HIV-related syndemics may partly drive excess CHEU health risks, highlighting an urgent need for holistic maternal and family care and support alongside ART to optimise the health of CHEU., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) predict viral breakthrough, but their use remains understudied in real-world clinic settings. This pilot study examined acceptability, feasibility, and initial adherence outcomes of providing adherence feedback using TFV-DP concentrations on patient- and provider-levels in Cape Town, South Africa. We enrolled 60 persons with HIV (PWH) receiving tenofovir-containing ART attending a primary health clinic. They were randomized 1:1 to an intervention receiving TFV-DP concentration feedback by research staff vs. no feedback at monthly visits for 4 months. Acceptability among medical providers and level of clinical follow-up of TFV-DP results was examined. Patient acceptability was assessed descriptively. Mean electronic adherence (EA), as measured by WisePill device, and TFV-DP in DBS were compared between the two arms. All participants in the intervention group (100%) reported finding TFV-DP feedback helpful and 86% reported changing adherence behaviors. Medical providers indicated high acceptability of incorporating TFV-DP concentration feedback into the clinic, yet among 29 results < 1000 fmol/punch, only 2 were reviewed with no follow-up actions performed. In the intervention arm, mean TFV-DP concentrations were significantly higher (t = 2.5, p < .01) during follow-up and EA in upper quartile (96-100%) was greater compared to controls (x 2  = 7.8, p ≤ .05). This study found high acceptability among patients for receiving adherence feedback based on TFV-DP concentrations. TFV-DP and EA data demonstrated greater adherence in the intervention group. Providers indicated high acceptability of incorporating TFV-DP feedback into the clinic, but few providers reviewed results, which could impact clinic-level feasibility., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Adolescent girls and young women (AGYW) in South Africa are at a higher risk of acquiring HIV. Despite the increasing availability of daily oral pre-exposure prophylaxis (PrEP) for HIV prevention, knowledge on PrEP use during pregnancy and postpartum periods at antenatal care (ANC) facilities remains inadequate., Methods: Data from HIV-uninfected pregnant women in Cape Town, South Africa, were used in this study. These women aged 16-24 years were enrolled in the PrEP in pregnancy and postpartum (PrEP-PP) cohort study during their first ANC visit. Using the PrEP cascade framework, the outcomes of the study were PrEP initiation (prescribed tenofovir disoproxil fumarate and emtricitabine at baseline), continuation (returned for prescription), and persistence [quantifiable tenofovir diphosphate (TFV-DP) in dried blood samples]. The two primary exposures of this study were risk perception for HIV and baseline HIV risk score (0-5), which comprised condomless sex, more than one sexual partner, partner living with HIV or with unknown serostatus, laboratory-confirmed sexually transmitted infections (STIs), and hazardous alcohol use before pregnancy (Alcohol Use Disorders Identification Test for Consumption score ≥ 3). Logistic regression was used to examine the association between HIV risk and PrEP, adjusting for a priori confounders., Results: A total of 486 pregnant women were included in the study, of which 16% were "adolescents" (aged 16-18 years) and 84% were "young women" (aged 19-24 years). The adolescents initiated ANC later than the young women [median = 28 weeks (20-34) vs. 23 weeks (16-34), p  = 0.04]. Approximately 41% of the AGYW were diagnosed with sexually transmitted infection at baseline. Overall, 83% of the AGYW initiated PrEP use during their first ANC. The percentage of PrEP continuation was 63% at 1 month, 54% at 3 months, and 39% at 6 months. Approximately 27% consistently continued PrEP use through 6 months, while 6% stopped and restarted on PrEP use at 6 months. With a higher risk score of HIV (≥2 vs. ≤1), the AGYW showed higher odds of PrEP continuation [adjusted odds ratio: 1.85 (95% CI: 1.12-3.03)] through 6 months, adjusting for potential confounders. Undergoing the postpartum period (vs. pregnant) and having lower sexual risk factors were found to be the barriers to PrEP continuation. TFV-DP concentration levels were detected among 49% of the AGYW, and 6% of these women had daily adherence to PrEP at 3 months., Conclusions: AGYW were found to have high oral PrEP initiation, but just over one-third of these women continued PrEP use through 6 months. Pregnant AGYW who had a higher risk of acquiring HIV (due to condomless sex, frequent sex, and STIs) were more likely to continue on PrEP use through the postpartum period. Pregnant and postpartum AGYW require counseling and other types of support, such as community delivery and peer support to improve their effective PrEP use through the postpartum period., Clinical Trial Number: ClinicalTrials.gov, NCT03826199., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Khadka, Gorbach, Nyemba, Mvududu, Mashele, Javanbakht, Nianogo, Aldrovandi, Bekker, Coates, Myer and Joseph Davey.)

Background: Left ventricular (LV) remodeling and its transitions from compensatory adaptations to LV dysfunction have not been examined in adolescents with perinatally acquired HIV infection (PHIV). We used cardiovascular magnetic resonance (CMR) in a cross-sectional study to characterize PHIV-related progressive LV remodeling in adolescents in South Africa., Methods: Adolescents with PHIV on antiretroviral treatment and their HIV uninfected peers completed 3 T CMR examination. We defined LV remodeling by LV mass/volume (M/V) ratio, modelling progressive LV remodeling as increasing M/V ratio. Linear regression models were applied to estimate the correlates of progressive LV remodeling., Results: Overall, 71 adolescents with PHIV [mean age: 15.2 years; 54% male] and 36 HIV uninfected [15.1 years; 42% male] peers were enrolled. Adolescents with PHIV had lower mean LV M/V ratio (0.68 vs. 0.75 g/mL; p = 0.004) than HIV uninfected peers, without LV hypertrophy in either group. Among adolescents with PHIV, increasing M/V ratio was accompanied by increasing interstitial volume [adjusted mean change (AMC) per 0.1 g/mL M/V ratio: 1.75 mL, p < 0.001] with no change in global circumferential strain (GCS) [AMC per 0.1 g/mL M/V ratio: -0.21%, p = 0.48]. However, in HIV uninfected individuals, increasing M/V ratio was accompanied by increasing peak GCS [AMC per 0.1 g/mL M/V ratio: -1.25%, p = 0.039] with no change in interstitial volume (AMC per 0.1 g/mL M/V ratio: 1.16 mL, p = 0.32]., Conclusions: Successfully treated PHIV is associated with less severe LV remodeling in adolescence when compared to HIV uninfected controls. LV remodeling in PHIV is associated with disproportionate expansion of the non-contractile interstitium not accompanied by improved GCS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Itai M. Magodoro reports financial support was provided by National Institutes of Health. Itai M. Magodoro reports financial support was provided by AIDS Healthcare Foundation. Heather Zar reports financial support was provided by National Institutes of Health. Heather Zar reports financial support was provided by South African Medical Research Council. Mark J. Siedner reports financial support was provided by National Institutes of Health., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART., Setting: Four primary health clinics in Cape Town, South Africa., Methods: We enrolled 250 virally suppressed PWH receiving tenofovir-based ART. We collected EA data, monthly viral load, and TFV-DP in DBS for 12 months. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for future viral breakthrough (VB) (>400 copies/mL) for each adherence measure. Receiver operating characteristics (ROCs) provided the predictive power of these measures., Results: Participants had a median (IQR) age of 34 (27-42); 78% were women. Twenty-one (8%) developed VB. Logistic regression showed that when percent EA and TFV-DP concentrations increased, the odds of VB decreased. This relationship was consistent at the time of VB (aOR of 0.41 [95% CI: 0.25 to 0.66] for TFV-DP and aOR of 0.64 [95% CI: 0.54 to 0.76] for EA) and for up to 2 months before VB. Both adherence measures predicted future VB at both 1 month and 2 months before viral load measurement., Conclusion: We established that 2 objective adherence measures, EA and TFV-DP in DBS, have a positive association with, and are both strongly predictive of, VB in a community-based South African cohort on ART. Future research is needed to determine the feasibility of implementing these adherence measures in resource-limited settings to facilitate adherence interventions., Competing Interests: C.O. has received honoraria from MSD. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In South Africa, at least 7.5 million people (age ≥15 years) are living with Human Immunodeficiency Virus (HIV). In 2020, 220,000 new infections occurred, approximately one-third of which were among cisgender adolescent girls and women (age ≥15 years). The perspectives of pregnant adolescent girls and young women (AGYW) as key, targeted end-users of pre-exposure prophylaxis (PrEP) in this setting are not well known., Methods: We purposively recruited participants enrolled in an ongoing cohort study at an urban antenatal clinic in Cape Town, South Africa for in-depth interviews between July-September 2020. We restricted our analysis to pregnant AGYW (age: 16-25 years) who initiated daily oral PrEP (Tenofovir/Emtricitabine) antenatally and self-reported either high PrEP persistence (≥25 days in the past 30 days and no missed PrEP collection), or low PrEP persistence and/or discontinuation (missing >5 days in the last 30 days or missed PrEP collection). The findings were organized thematically, per the adapted Health Behavior Model (2000), using Nvivo -v.1.5., Results: We interviewed 18 AGYW (mean age = 22 years), at a mean of 14 weeks postpartum. Higher self-esteem and high-quality study provider-client relationships, including empathic psychosocial support, facilitated PrEP continuation. Reported barriers included unstable social structure characteristics (i.e., financial hardship) and individual factors (i.e., unintended pregnancy, parental rejection, and inadequate peer- and [non-cohabiting] partner support). Participants self-perceived a need for PrEP, feeling susceptible to non-consensual, forced sex, or considering partners' (presumed) sexual risk-taking. Limited community awareness regarding PrEP availability and/or perceived complexity in navigating health system access to PrEP, impede continuation., Conclusions: PrEP-focused healthcare access pathways for pregnant and postpartum AGYW need to be simplified. Further research is needed on health system determinants (i.e., structural barriers, provider-client interactions, and related outcomes) of oral PrEP utilization. In 2022, South Africa announced regulatory approval of long-acting PrEP options (i.e., the dapivirine ring for non-pregnant women and injectable cabotegravir, respectively); these may mitigate implementation barriers reported in this study. However, the safety and efficacy of long-acting PrEP (e.g., injectables, implants) among pregnant or breastfeeding women, specifically, remains to be confirmed in this setting.

Background: Mobile health (mHealth) initiatives are increasingly common in low-resource settings, but the appropriateness of smartphone interventions in health care settings is uncertain. More research is needed to establish the appropriateness and feasibility of integrating new mHealth modalities (novel apps and social media apps) in the South African context., Objective: In this study, to inform future mHealth interventions, we describe smartphone ownership, preferences, and usage patterns among pregnant women living with HIV in Gugulethu, South Africa., Methods: We screened pregnant women living with HIV from December 2019 to February 2021 for the CareConekta trial. To be enrolled in the trial, respondents were required to be 18 years of age or older, living with HIV, ≥28 weeks pregnant, and own a smartphone that met the technical requirements of the CareConekta app. In this secondary analysis, we describe mobile phone ownership and sociodemographic characteristics of all women screened for eligibility (n=639), and smartphone use patterns among those enrolled in the trial (n=193)., Results: Overall, median age was 31 (IQR 27-35) years. Of the 582 women who owned smartphones, 580 responded to the question about whether or not it was a smartphone, 2 did not. Among those with smartphones, 92% (421/458) of them used the Android operating system of version 5.0 or above, 98% (497/506) of phones had a GPS, and 96% (485/506) of individuals charged their phones less than twice a day. Among women who were enrolled in the trial, nearly all (99%, 190/193) owned the smartphone themselves; however, 14% (26/193) shared their smartphone with someone. In this case, 96% (25/26) reported possessing the phone most of the day. Median duration of ownership of the smartphone was 12 (IQR 5-24) months, median duration with current phone number use was 25 (IQR 12-60) months, and median number of cell phone numbers owned 2 years prior to enrollment in the trial was 2 (IQR 1-2). Receiving (192/193, 99.5%) and making (190/193, 99%) phone calls were among the most common smartphone uses. The least used features were GPS (106/193, 55%) and email (91/193, 47%). WhatsApp was most frequently reported as a favorite app (181/193, 94%)., Conclusions: Smartphone ownership is very common among pregnant women living with HIV in this low-resource, periurban setting. Phone sharing was uncommon, nearly all used the Android system, and phones retained sufficient battery life. These results are encouraging to the development of mHealth interventions. Existing messaging platforms-particularly WhatsApp-are exceedingly popular and could be leveraged for interventions. Findings of moderate smartphone ownership turnover and phone number turnover are considerations for mHealth interventions in similar settings., Trial Registration: ClinicalTrials.gov NCT03836625; https://clinicaltrials.gov/ct2/show/NCT03836625?term=NCT03836625., (©Sandisiwe Noholoza, Tamsin K Phillips, Sindiswa Madwayi, Megan Mrubata, Carol S Camlin, Landon Myer, Kate Clouse. Originally published in JMIR Formative Research (https://formative.jmir.org), 22.06.2023.)

Background: Service providers' attitudes toward interventions are essential for adopting and implementing novel interventions into healthcare settings, but evidence of evaluations in the HIV context is still limited. This study is part of the CombinADO cluster randomized trial (ClinicalTrials.gov NCT04930367), which is investigating the effectiveness of a multi-component intervention package (CombinADO strategy) aimed at improving HIV outcomes among adolescents and young adults living with HIV (AYAHIV) in Mozambique. In this paper we present findings on key stakeholder attitudes toward adopting study interventions into local health services., Methods: Between September and December 2021, we conducted a cross-sectional survey with a purposive sample of 59 key stakeholders providing and overseeing HIV care among AYAHIV in 12 health facilities participating in the CombinADO trial, who completed a 9-item scale on attitudes towards adopting the trial intervention packages in health facilities. Data were collected in the pre-implementation phase of the study and included individual stakeholder and facility-level characteristics. We used generalized linear regression to examine the associations of stakeholder attitude scores with stakeholder and facility-level characteristics., Results: Overall, service-providing stakeholders within this setting reported positive attitudes regarding adopting intervention packages across study clinic sites; the overall mean total attitude score was 35.0 ([SD] = 2.59, Range = [30-41]). The study package assessed (control or intervention condition) and the number of healthcare workers delivering ART care in participating clinics were the only significant explanatory variables to predict higher attitude scores among stakeholders (β = 1.57, 95% CI = 0.34-2.80, p = 0.01 and β = 1.57, 95% CI = 0.06-3.08, p = 0.04 respectively)., Conclusions: This study found positive attitudes toward adopting the multi-component CombinADO study interventions among HIV care providers for AYAHIV in Nampula, Mozambique. Our findings suggest that adequate training and human resource availability may be important in promoting the adoption of novel multi-component interventions in healthcare services by influencing healthcare provider attitudes., (© 2023. The Author(s).)

We have previously shown accelerated ageing in adolescents perinatally infected with HIV (PHIV +), based on discrepancies between epigenetic and chronological age. The current study examines follow-up longitudinal patterns of epigenetic ageing and the association of epigenetic ageing with cognition as well as whole brain structure changes in PHIV + and healthy controls enrolled in the Cape Town Adolescent Antiretroviral Cohort Study (CTAAC). The Illumina EPIC array was used to generate blood DNA methylation data from 60 PHIV + adolescents and 36 age-matched controls aged 9-12 years old at baseline and again at a 36-month follow-up. Epigenetic clock software estimated two measures of epigenetic age acceleration: extrinsic epigenetic accelerated ageing (EEAA) and age acceleration difference (AAD) at both time points. At follow-up, each participant completed neuropsychological testing, structural magnetic resonance imaging, and diffusion tensor imaging. At follow-up, PHIV infection remains associated with increased EEAA and AAD. Accelerated epigenetic ageing remained positively associated with viral load and negatively associated with CD4 ratio. EEAA was positively associated with whole brain grey matter volume and alterations in whole brain white matter integrity. AAD and EEAA were not associated with cognitive function within the PHIV + group. Measures of epigenetic ageing, as detected in DNA methylation patterns, remain increased in PHIV + adolescents across a 36-month period. Associations between epigenetic ageing measures, viral biomarkers, and alterations in brain micro- and macrostructure also persist at 36-month follow-up. Further study should determine if epigenetic age acceleration is associated with cognitive functional changes due to brain alterations in later life., (© 2023. The Author(s).)

Background: Mobile health interventions are common in public health settings in Africa, and our preliminary work showed that smartphones are increasing in South Africa. We developed a novel smartphone app-CareConekta-that used GPS location data to characterize personal mobility to improve engagement in HIV care among pregnant and postpartum women living with HIV in South Africa. The app also used the user's location to map nearby clinics., Objective: We aimed to describe the feasibility, acceptability, and initial efficacy of using the app in a real-world setting., Methods: We conducted a prospective randomized controlled trial at a public sector clinic near Cape Town, South Africa. We enrolled 200 pregnant (third trimester) women living with HIV who owned a smartphone that met the required specifications. All participants installed the app, designed to collect 2 GPS heartbeats per day to geolocate the participant within a random 1-km fuzzy radius (for privacy). We randomized (1:1) participants to a control arm to receive the app with no additional support or an intervention arm to receive supportive phone calls, WhatsApp (Meta Platforms, Inc) messages, or both from the study team when traveling >50 km from the study area for >7 days. In addition to mobility data collected daily through the phone, participants completed questionnaires at enrollment and follow-up (approximately 6 months post partum)., Results: A total of 7 participants were withdrawn at enrollment or shortly after because of app installation failure (6/200, 3%) or changing to an unsuitable phone (1/200, 0.50%). During the study period, no participant's smartphone recorded at least 1 heartbeat per day, which was our primary feasibility measure. Of the 171 participants who completed follow-up, only half (91/171, 53.2%) reported using the same phone as that used at enrollment, with the CareConekta app still installed on the phone and GPS usually enabled. The top reasons reported for the lack of heartbeat data were not having mobile data, uninstalling the app, and no longer having a smartphone. Acceptability measures were positive, but participants at follow-up demonstrated a lack of understanding of the app's purpose and function. The clinic finder was a popular feature. Owing to the lack of consistent GPS heartbeats throughout the study, we were unable to assess the efficacy of the intervention., Conclusions: Several key challenges impeded our study feasibility. Although the app was designed to reverse bill participants for any data use, the lack of mobile data was a substantial barrier to our study success. Participants reported purchasing WhatsApp data, which could not support the app. Problems with the web-based dashboard meant that we could not consistently monitor mobility. Our study provides important lessons about implementing an ambitious GPS-based study under real-world conditions in a limited-resource setting., Trial Registration: ClinicalTrials.gov NCT03836625; https://clinicaltrials.gov/ct2/show/NCT03836625., International Registered Report Identifier (irrid): RR2-10.1186/s13063-020-4190-x., (©Kate Clouse, Sandisiwe Noholoza, Sindiswa Madwayi, Megan Mrubata, Carol S Camlin, Landon Myer, Tamsin K Phillips. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 19.05.2023.)

Background: Point-of-care (POC) nucleic acid testing for diagnosis of HIV in infants facilitates earlier initiation of antiretroviral therapy (ART) than with centralised (standard-of-care, SOC) testing, but can be more expensive. We evaluated cost-effectiveness data from mathematical models comparing POC with SOC to provide global policy guidance., Methods: In this systematic review of modelling studies, we searched PubMed, MEDLINE, Embase, the National Health Service Economic Evaluation Database, Econlit, and conference abstracts, combining terms for "HIV" + "infant"/"early infant diagnosis" + "point-of-care" + "cost-effectiveness" + "mathematical models", without restrictions from database inception to July 15, 2022. We selected reports of mathematical cost-effectiveness models comparing POC with SOC for HIV diagnosis in infants younger than 18 months. Titles and abstracts were independently reviewed, with full-text review for qualifying articles. We extracted data on health and economic outcomes and incremental cost-effectiveness ratios (ICERs) for narrative synthesis. The primary outcomes of interest were ICERs (comparing POC with SOC) for ART initiation and survival of children living with HIV., Findings: Our search identified 75 records through database search. 13 duplicates were excluded, leaving 62 non-duplicate articles. 57 records were excluded and five were reviewed in full text. One article was excluded as it was not a modelling study, and four qualifying studies were included in the review. These four reports were from two mathematical models from two independent modelling groups. Two reports used the Johns Hopkins model to compare POC with SOC for repeat early infant diagnosis testing in the first 6 months in sub-Saharan Africa (first report, simulation of 25 000 children) and Zambia (second report, simulation of 7500 children). In the base scenario, POC versus SOC increased probability of ART initiation within 60 days of testing from 19% to 82% (ICER per additional ART initiation range US$430-1097; 9-month cost horizon) in the first report; and from 28% to 81% in the second ($23-1609, 5-year cost horizon). Two reports compared POC with SOC for testing at 6 weeks in Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Paediatric model (simulation of 30 million children; lifetime horizon). POC increased life expectancy and was considered cost-effective compared with SOC (ICER $711-850 per year of life saved in HIV-exposed children). Results were robust throughout sensitivity and scenario analyses. In most scenarios, platform cost-sharing (co-use with other programmes) resulted in POC being cost-saving compared with SOC., Interpretation: Four reports from two different models suggest that POC is a cost-effective and potentially cost-saving strategy for upscaling of early infant testing compared with SOC., Funding: Bill & Melinda Gates Foundation, Unitaid, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, WHO, and Massachusetts General Hospital Research Scholars., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Long-acting pre-exposure prophylaxis (PrEP) options could overcome barriers to oral PrEP persistence during pregnancy and postpartum. We evaluated long-acting PrEP preferences among oral PrEP-experienced pregnant and postpartum women in South Africa and Kenya, countries with high PrEP coverage with pending regulatory approvals for long-acting injectable cabotegravir and the dapivirine vaginal ring (approved in South Africa, under review in Kenya)., Methods: From September 2021 to February 2022, we surveyed pregnant and postpartum women enrolled in oral PrEP studies in South Africa and Kenya. We evaluated oral PrEP attitudes and preferences for long-acting PrEP methods in multivariable logistic regression models adjusting for maternal age and country., Results: We surveyed 190 women in South Africa (67% postpartum; median age 27 years [IQR = 22-32]) and 204 women in Kenya (79% postpartum; median age 29 years [IQR = 25-33]). Seventy-five percent of participants reported oral PrEP use within the last 30 days. Overall, forty-nine percent of participants reported negative oral PrEP attributes, including side effects (21% South Africa, 30% Kenya) and pill burden (20% South Africa, 25% Kenya). Preferred PrEP attributes included long-acting method, effectiveness, safety while pregnant and breastfeeding, and free medication. Most participants (75%, South Africa and Kenya) preferred a potential long-acting injectable over oral PrEP, most frequently for a longer duration of effectiveness in South Africa (87% South Africa, 42% Kenya) versus discretion in Kenya (5% South Africa, 49% Kenya). Eighty-seven percent of participants preferred oral PrEP over a potential long-acting vaginal ring, mostly due to concern about possible discomfort with vaginal insertion (82% South Africa, 48% Kenya). Significant predictors of long-acting PrEP preference included past use of injectable contraceptive (aOR = 2.48, 95% CI: 1.34, 4.57), disliking at least one oral PrEP attribute (aOR = 1.72, 95% CI: 1.05, 2.80) and preferring infrequent PrEP use (aOR = 1.58, 95% CI: 0.94, 2.65)., Conclusions: Oral PrEP-experienced pregnant and postpartum women expressed a theoretical preference for long-acting injectable PrEP over other modalities, demonstrating potential acceptability among a key population who must be at the forefront of injectable PrEP rollout. Reasons for PrEP preferences differed by country, emphasizing the importance of increasing context-specific options and choice of PrEP modalities for pregnant and postpartum women., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)