Clinical, pharmacological, and qualitative characterization of drug-drug interactions in pregnant women initiating HIV therapy in Sub-Saharan Africa.

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.

Cost-Effectiveness of Dolutegravir Compared With Efavirenz for Prevention of Perinatal Transmission in Women Presenting With HIV in Late Pregnancy in Uganda.

OBJECTIVES: Dolutegravir (DTG) has proved to be more efficacious, tolerable, and safer than efavirenz (EFV) among mothers living with HIV and their infants in Uganda. This study assessed the cost-effectiveness of the DTG-based antiretroviral therapy (ART) compared with the standard of care for preventing perinatal transmissions among pregnant women initiating ART in late pregnancy in Uganda. METHODS: We used data from a randomized open-label trial (DolPHIN-2) and a 2-part cost-effectiveness model composed of a short-term decision tree to estimate the perinatal transmission rate and costs and an individual-based 3-state Markov model (HIV, advanced HIV, dead) to estimate the long-term costs and health outcomes from the Ugandan payer perspective using a lifetime horizon and a 1-year Markov cycle. The main outcomes were the mean annual costs in US dollars ($), disability-adjusted life-years (DALYs), and incremental cost-effectiveness ratio. Both the deterministic and probabilistic sensitivity analyses were conducted to assess the effect of parameter uncertainties on the ultimate results and the model's robustness. RESULTS: Compared with the EFV-based ART, the DTG-based ART was associated with fewer mean annual costs ($43.58 vs $68.44) and DALYs (0.33 vs 0.56), leading to cost savings of $110 per DALY averted. In the incremental analysis, the DTG-based ART dominated the EFV-based ART; that is, it was less costly and more effective. These results were robust to deterministic and probabilistic sensitivity analyses. CONCLUSION: The DTG-based ART is a highly cost-effective strategy compared with the EFV-based ART among women initiating treatment in the third trimester of pregnancy in a low-income setting.

Gestational weight gain and adverse birth outcomes in South African women with HIV on antiretroviral therapy and without HIV: a prospective cohort study.

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/m2 (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.

Cardioprotective effects of early versus late initiated antiretroviral treatment in adolescents with perinatal HIV-1 infection.

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.

Experiences of transfer of care among postpartum women living with HIV attending primary healthcare services in South Africa.

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.

Effect of prior tuberculosis on cardiovascular status in perinatally HIV-1-infected adolescents.

Whether, and how, co-occurring HIV-1 infection (HIV) and tuberculosis (TB) impact cardiovascular status, especially in adolescents with perinatally acquired HIV (APHIV), have not been examined. We hypothesized that APHIV with previous active TB have worse cardiac efficiency than APHIV without TB, which is mediated by increased inflammation. Arterial elastance (Ea) and ventricular end-systolic elastance (Ees) were assessed by cardiovascular magnetic resonance, and ventriculoarterial coupling (VAC) estimated as Ea/Ees ratio. Inflammation was measured by high sensitivity C-reactive protein (hsCRP). Previous TB in APHIV was associated with reduced cardiac efficiency, related to an altered ventriculoarterial coupling. However, we did not find evidence of hsCRP mediated effects in the association between prior TB and cardiac efficiency. The clinical significance of these findings requires further study, including a wider range of biomarkers of specific immune pathways.

ART history prior to conception: trends and association with postpartum disengagement from HIV care in Khayelitsha, South Africa (2013-2019): a retrospective cohort study.

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.

Cardioprotective effects of antiretroviral treatment in adolescents with perinatal HIV infection are heterogeneous depending on age at treatment initiation.

The cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) may depend on age at ART initiation. We used cardiovascular magnetic resonance (CMR) to characterize and compare residual cardiac changes in apparently healthy APHIV with early and delayed ART initiation compared to sex- and age-similar HIV uninfected peers. We defined early and delayed ART as, respectively, treatment initiated at <5 years and ≥5 years of age. Cardiac function, mechanical deformation, geometry and tissue composition were assessed. APHIV had distinct albeit subclinical cardiac phenotypes depending on timing of ART initiation. For example, 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.

Support, not blame: safe partner disclosure among women diagnosed with HIV late in pregnancy in South Africa and Uganda.

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.

Inflammatory markers in pregnancy are associated with postpartum weight in South African women living with HIV on antiretroviral therapy.

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.

Cardiometabolic Health in Pregnancy and Postpartum: Findings From a Prospective Cohort Study in South Africa.

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/m2), 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.

Transfers between health facilities of people living with diabetes attending primary health care services in the Western Cape Province of South Africa: A retrospective cohort study.

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.

"So that's why I found PrEP to be safest way to protect yourself": exploring IPV experiences and impact on HIV prevention among pregnant and postpartum women in Cape Town, South Africa.

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.

Measurement of body composition in postpartum South African women living with and without HIV infection.

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.

Peripartum mobility and maternal/child separation among women living with HIV in South Africa.

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.

Comparison of dolutegravir and efavirenz on depression, anxiety and sleep disorders in pregnant and postpartum women living with HIV.

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.

Comparing a point-of-care urine tenofovir lateral flow assay to self-reported adherence and their associations with viral load suppression among adults on antiretroviral therapy.

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.

The potential benefits of long-acting injectable cabotegravir in pregnant and breastfeeding women and their infants.

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.