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.

HIV-related stigma, disclosure and social support: experiences among young pregnant and postpartum women living with HIV in South Africa.

ABSTRACTYoung pregnant and postpartum women living with HIV (WLHIV) are at high risk of poor antiretroviral therapy (ART) outcomes, which may be driven partly by HIV-related stigma. We conducted in-depth interviews with 20 pregnant and postpartum WLHIV aged 19-24 years to understand how different forms of HIV-related stigma manifest in their lives, as well as their experiences of HIV-status disclosure and social support. Participants described profound levels of perceived stigma in their community, including gossip from other young women and judgement from older adults. Consequently, participants disclosed to a limited number of people to avoid being stigmatised, and disclosure to peers was especially uncommon. However, disclosure in certain situations was described as leading to emotional support and support for ART adherence, and disclosure to older WLHIV resulted in participants having a role model. Finally, participants expressed varied ways in which they accept, speak about, and live with their HIV diagnosis. These data provide a rich understanding of the experiences of HIV-related stigma in this population and point to the need for psychosocial interventions focussed on acceptance and coping with an HIV-positive diagnosis despite profound levels of perceived stigma, as well as navigating decisions around the targets and timing of disclosure.Trial registration: ClinicalTrials.gov identifier: NCT04036851.

Impact of adverse childhood experiences on women's psychosocial and HIV-related outcomes and early child development in their offspring.

Adverse childhood experiences (ACEs) may have a critical influence on adult outcomes and subsequent offspring development, but few data have explored the effects of ACEs in low-resource settings where the burdens of childhood adversity and HIV are high. Among mothers living with HIV in Cape Town, we examined the effects of ACEs on maternal psychosocial and HIV-related outcomes, as well as early child development in their offspring aged 36-60 months. The World Health Organization's Adverse Childhood Experiences International Questionnaire was used to measure maternal reports of ACEs, and the Ages & Stages Questionnaire to screen for developmental delays in their offspring. Among 353 women (median age: 32 years), 84% reported ≥1 ACEs. Increased report of ACEs was strongly associated with depressive symptoms, hazardous alcohol use, intimate partner violence and self-reported suboptimal adherence to antiretroviral therapy. These associations were driven by more severe childhood experiences, including abuse, neglect and exposure to collective violence. Among 255 women who reported on their child's development, maternal ACEs were associated with poorer socioemotional development. These data suggest that childhood adversity has long-term effects on maternal outcomes as well as their children's socioemotional development and point to ACEs that might be targeted for screening and intervention.

"I had Made the Decision, and No One was Going to Stop Me" -Facilitators of PrEP Adherence During Pregnancy and Postpartum in Cape Town, South Africa.

PrEP is safe and effective but requires adherence during potential HIV exposure, yet the facilitators of long-term maternal adherence are not well understood. We conducted semi-structured interviews with 25 postpartum women who reported high adherence (PrEP use ≥ 25 days in last 30-days and never missed a PrEP prescription in pregnancy/postpartum period) within a PrEP service for pregnant and postpartum women. A thematic approach guided an iterative process of coding and analysis. Themes identified as drivers of optimal PrEP use were HIV risk perception, mainly because of partner's behaviors and unknown serostatus, and a strong desire to have a baby free of HIV. Reported disclosure of PrEP use facilitated PrEP adherence. Women discussed having partner and family support, which included reminders to take PrEP daily. Primary barriers were anticipated or experienced stigma, overcome through education of partners and family about PrEP. Pregnant women experienced transient side-effects, but found ways to continue, including taking PrEP at night. PrEP programs for pregnant and postpartum women should integrate strategies to assist women with realistic appraisals of risk and teach skills for disclosure and securing support from significant others.

RESUMEN: La profilaxis Pre-exposición (PrEP, siglas en inglés) es segura y eficaz, pero requiere adherencia durante una posible exposición al VIH; sin embargo, no se conocen bien los factores que facilitan la adherencia materna a largo plazo. Realizamos entrevistas semiestructuradas con 25 mujeres en posparto que informaron un alto cumplimiento (uso de PrEP> 25 días en los últimos 30 días y nunca omitieron una receta de PrEP en el embarazo y período posparto) dentro de un servicio de PrEP para mujeres embarazadas y posparto. Un enfoque temático guio un proceso iterativo de codificación y análisis. Los temas identificados como impulsores del uso óptimo de la PrEP fueron la percepción del riesgo de VIH, principalmente debido a los comportamientos de la pareja y el estado serológico desconocido, y un fuerte deseo de tener un bebé libre de VIH. La divulgación informada del uso de PrEP facilitó la adherencia a la PrEP. Las mujeres hablaron sobre el apoyo de su pareja y familia, incluidos recordatorios para tomar la PrEP cada dia. Las barreras primarias fueron el estigma anticipado o experimentado, superado a través de la educación de los socios y familiares sobre la PrEP. Las mujeres embarazadas experimentaron efectos secundarios transitorios, pero encontraron formas de continuar, incluida la toma de PrEP por la noche. Los programas de PrEP para mujeres embarazadas y posparto deben integrar estrategias para ayudar a las mujeres con evaluaciones realistas del riesgo y enseñar habilidades para la divulgación y obtener el apoyo de otras personas importantes.

Mother-child separation among women living with HIV and their children in the first four years postpartum in South Africa.

OBJECTIVES: Mother-child pairs may separate during early life, yet the health impacts thereof are unclear. We explored the patterns and impact of separation among women living with HIV (WLHIV) and their children in South Africa. METHODS: WLHIV who had initiated antiretroviral therapy (ART) during pregnancy received HIV viral load (VL) testing and completed a timeline questionnaire of mother-child separation since delivery at 3-5 years post-partum. Health care usage was abstracted from routine medical records. We examined associations between separation and (a) maternal health outcomes (engagement in HIV care and HIV viral suppression, [VS]) and (b) child health outcomes (post-breastfeeding HIV testing and immunisation completion), using logistic regression. RESULTS: Of 346 mother-child pairs (median maternal age at antenatal ART initiation, 28 years), 24% were ever separated (median time to first separation 20 months, interquartile range [IQR] 9, 31). Most separated children were living with their grandmothers (65/83, 78%). Mothers who ever separated were younger, and more likely to be employed, and to reside in informal housing than those who never separated. Any separation reduced the odds of VS ≤ 50 copies/mL at four years post-partum (odds ratio 0.57; 95% CI 0.34-0.93); associations were similar for VL ≤ 1000 copies/mL and maternal engagement in care. No association was found between separation and child confirmatory HIV testing or immunisation completion. CONCLUSIONS: In this setting, mother-child separation is common in the first four years of life and appears associated with suboptimal maternal outcomes. Further research is required to understand the drivers and implications of mother-child separation.

OBJECTIFS: Les couples mère-enfant peuvent être séparés au début de la vie, mais les effets sur la santé ne sont pas clairs. Nous avons exploré les modèles et l'impact de la séparation chez les femmes vivant avec le VIH (PVVIH) et leurs enfants en Afrique du Sud. MÉTHODES: Les PVVIH qui avaient initié un traitement antirétroviral (ART) pendant la grossesse ont subi un test de charge virale du VIH (CV) et ont rempli un questionnaire chronologique sur la séparation mère-enfant depuis l'accouchement à 3-5 ans post-partum. L'utilisation des soins de santé a été extraite des dossiers médicaux de routine. Nous avons examiné les associations entre la séparation et (a) les résultats pour la santé maternelle (engagement dans les soins du VIH et la suppression virale du VIH [SV]) et (b) les résultats pour la santé de l'enfant (dépistage du VIH après l'allaitement et achèvement de la vaccination), en utilisant la régression logistique. RÉSULTATS: Sur 346 couples mère-enfant (âge maternel médian au début de l'ART prénatal, 28 ans), 24% ont été séparés (délai médian jusqu'à la première séparation 20 mois, intervalle interquartile [IQR] 9 à 31). La plupart des enfants séparés vivaient avec leurs grands-mères (65/83, 78%). Les mères qui ont vécu une telle séparation étaient plus jeunes et plus susceptibles d'avoir un emploi et de vivre dans un logement informel que celles qui ne l'ont jamais vécue. Toute séparation réduisait les chances de SV ≤50 copies/mL à quatre ans après l'accouchement (odds ratio 0,57; IC95%: 0,34-0,93); les associations étaient similaires pour la CV ≤1000 copies/mL et l'engagement de la mère dans les soins. Aucune association n'a été trouvée entre la séparation et le test de confirmation du VIH chez l'enfant ou l'achèvement de la vaccination. CONCLUSIONS: Dans ce contexte, la séparation mère-enfant est courante au cours des quatre premières années de la vie et semble associée à des résultats maternels sous-optimaux. Des recherches supplémentaires sont nécessaires pour comprendre les facteurs et les implications de la séparation mère-enfant.

Long-Term Outcomes of HIV-Infected Women Receiving Antiretroviral Therapy After Transferring Out of an Integrated Maternal and Child Health Service in South Africa.

BACKGROUND: Integrated maternal and child health (MCH) services improve women's postpartum antiretroviral therapy (ART) outcomes during breastfeeding; however, long-term outcomes after transfer to general ART services remain unknown. METHODS: The MCH-ART trial demonstrated that maternal retention and viral suppression at 12-months postpartum were improved significantly among women randomized to integrated MCH services continued in the antenatal clinic through cessation of breastfeeding (MCH-ART arm) compared with immediate transfer to general ART services postpartum (standard of care). We reviewed electronic health records for all women who participated in the MCH-ART trial to ascertain retention and gaps in care and invited all women for a study visit 36- to 60-months postpartum including viral load testing. RESULTS: Of 471 women in MCH-ART, 450 (96%) contributed electronic health record data and 353 (75%) completed the study visit (median 44-month postpartum). At this time, outcomes were identical in both trial arms: 67% retained in care (P = 0.994) and 56% with viral loads <50 copies/mL (P = 0.751). Experiencing a gap in care after delivery was delayed in the MCH-ART arm with 17%, 36%, and 45% of women experienced a gap in care by 12-, 24-, and 36-months postpartum compared with 35%, 48%, and 57% in the standard of care arm, respectively. CONCLUSIONS: The benefits of integrated maternal HIV and child health care did not persist after transfer to general ART services. The transfer of women postpartum to routine adult care is a critical period requiring interventions to support continuity of HIV care.

Prevalence and correlates of sexually transmitted infections in pregnancy in HIV-infected and- uninfected women in Cape Town, South Africa.

OBJECTIVES: Sexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine. METHODS: Between November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy. RESULTS: In 242 women (median age 29 years [IQR = 24-34], median gestation 19 weeks [IQR = 14-24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02-3.67), being unmarried or not cohabiting with the fetus' father (aOR = 2.19; 95% CI = 1.16-4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08-20.95) were associated with STI diagnosis. CONCLUSION: We found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy.

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

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

Modelling the potential impact of providing preexposure prophylaxis in pregnant and breastfeeding women in South Africa.

OBJECTIVE: HIV-uninfected pregnant and breastfeeding women are at high risk of HIV acquisition, contributing to vertical transmission of HIV. Preexposure prophylaxis (PrEP) is safe in pregnancy, but PrEP in pregnancy is not policy in many countries including South Africa. We evaluated the potential impact of providing PrEP for pregnant/breastfeeding women using a HIV model for South Africa. METHODS: Our model considers two scenarios: a conservative scenario that matches the experience reported in the Kenyan PrEP programme for pregnant women (probability of uptake = 32% and 11% in high-risk and low-risk women, respectively); and an optimistic scenario with PrEP initiated by 80% of all pregnant women. We compared this with PrEP for female sex workers, MSM and adolescent girls/young women. Women are assumed to remain on PrEP throughout pregnancy and breastfeeding, and an equivalent average PrEP duration (2 years) is assumed in other scenarios. RESULTS: Between 2020 and 2030, if PrEP is provided to pregnant/breastfeeding mothers, we project a 2.5% reduction in total HIV transmission [95% credibility interval (CI): 2.4-2.6%] in the conservative scenario and 7.2% (95% CI: 6.8-7.5%) in the optimistic scenario, which is similar to that in the female sex worker and MSM PrEP scenarios (1.9% and 3.0%, respectively). Without PrEP, 76 000 (95% CI: 64 000-90 000) new cases of vertical transmission are expected; PrEP provision may reduce these infections by 13% (95% CI: 13-14%) in the conservative scenario and 41% (95% CI: 39-44%) in the optimistic scenario. CONCLUSION: High levels of uptake of and adherence to PrEP among pregnant/breastfeeding women could substantially reduce maternal and infant HIV acquisition in South Africa.

A Comparison of Plasma Efavirenz and Tenofovir, Dried Blood Spot Tenofovir-Diphosphate, and Self-Reported Adherence to Predict Virologic Suppression Among South African Women.

BACKGROUND: Tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) is an objective long-term adherence measure, but data are limited on its ability to predict virologic suppression (VS) in people on antiretroviral (ARV) treatment. There are also no data comparing DBS TFV-DP with plasma ARV concentrations as predictors of VS. METHODS: Women who were on a first-line regimen of tenofovir, emtricitabine, and efavirenz (EFV) were enrolled in a cross-sectional study. Plasma EFV and tenofovir (TFV), DBS TFV-DP assays, and 30-day self-reported adherence were evaluated as predictors of VS (<50 copies/mL) with the area under the curve of receiver operating characteristics and logistic regression. RESULTS: We enrolled 137 women; mean age of 33 years; median 4 years on antiretroviral therapy; 88 (64%) had VS. In receiver operating characteristics analyses: DBS TFV-DP [0.926 (95% CI: 0.876 to 0.976)] had a higher area under the curve than plasma TFV [0.864 (0.797 to 0.932); P = 0.006], whereas plasma EFV [0.903 (0.839-0.967)] was not significantly different from DBS TFV-DP (P = 0.138) or plasma TFV (P = 0.140); all ARV assays performed better than self-report. The association of TFV-DP in DBS with VS strengthened with increasing concentrations [reference <350 fmol/punch: 350-699 fmol/punch aOR 37 (8-178); 700-1249 fmol/punch aOR 47 (13-175); ≥1250 fmol/punch aOR 175 (20-1539)]. "White coat adherence" (defined as DBS TFV-DP <350 fmol/punch with detectable plasma TFV) was only detected in 4 women. CONCLUSIONS: Plasma EFV, TFV, and DBS TFV-DP were all strong predictors of VS. EFV or TFV assays have potential for development as point-of-care assays for use as objective adherence measures in resource-limited settings.

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

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

Risk perception and sex behaviour in pregnancy and breastfeeding in high HIV prevalence settings: Programmatic implications for PrEP delivery.

HIV acquisition during pregnancy and breastfeeding significantly contributes toward paediatric HIV infection; however, little is known about risk behaviours in HIV-uninfected pregnant and postpartum women. We conducted twenty-six in-depth-interviews between July and December 2016 using a semi-structured interview guide among HIV-uninfected pregnant and recently postpartum women at-risk of HIV acquisition (defined as reporting ≥1 of the following: partner's serostatus unknown or HIV-infected, recent condomless sex in pregnancy, and/or alcohol use during pregnancy) who attended primary healthcare services. Our study contextualizes factors related to risky sexual behaviours during pregnancy and postpartum periods and assesses knowledge and hypothetical acceptability of pre-exposure prophylaxis (PrEP) in pregnancy. Translated and transcribed data were coded and analysed by three researchers using a thematic analysis approach. In interviews with HIV-uninfected pregnant/postpartum women at-risk of HIV acquisition, we identified common themes associated with sexual risk behaviours during pregnancy, including: lack of control over decisions in sex and condom use in pregnancy, low perceived risk (e.g. beliefs that their partner has the same HIV-negative serostatus), and socio-cultural beliefs around condom use during pregnancy (e.g. contact with sperm is essential for baby's development). PrEP knowledge was low among HIV-uninfected pregnant and breastfeeding women, and potential acceptability was good, though primary concerns were around the potential impact on the infant. While mothers presented a clear desire to protect themselves from HIV acquisition once pregnant, they also reported lack of control, and socio-cultural beliefs, like sex is good for the baby, that increased their risk of seroconversion. Mothers had limited PrEP awareness but reported hypothetical willingness to use PrEP because of concerns over HIV acquisition and onward mother to child transmission.

Sexual risk during pregnancy and postpartum periods among HIV-infected and -uninfected South African women: Implications for primary and secondary HIV prevention interventions.

BACKGROUND: HIV acquisition in pregnancy and breastfeeding contributes significantly toward pediatric HIV infection. However, little is known about how sexual behavior changes during pregnancy and postpartum periods which will help develop targeted HIV prevention and transmission interventions, including pre-exposure prophylaxis (PrEP). METHODS: Cross-sectional study in HIV-infected and uninfected pregnant and postpartum women in Cape Town, South Africa. Interviewers collected survey data on demographic, sexual behaviors, and alcohol use among pregnant and post-partum women. We report descriptive results of sexual behavior by trimester and postpartum period, and results of multivariable logistic regression stratified by pregnancy status. RESULTS: We enrolled 377 pregnant and postpartum women (56% pregnant, 40% HIV-infected). During pregnancy, 98% of women reported vaginal sex (8% anal sex, 44% oral sex) vs. 35% and 88% during the periods 0-6 and 7-12 months postpartum, respectively (p<0.05). More pregnant women reported having >1 partner in the past 12-months compared to postpartum women (18% vs. 13%, respectively, p<0.05). Sex frequency varied by trimester with greatest mean sex acts occurring during first trimester and >6-months postpartum (13 mean sex acts in first trimester; 17 mean sex acts >6-months postpartum). Pregnant women had increased odds of reporting condomless sex at last sex (aOR = 2.96;95%CI = 1.84-4.78) and ever having condomless sex in past 3-months (aOR = 2.65;95%CI = 1.30-5.44) adjusting for age, HIV status, and sex frequency compared to postpartum women. CONCLUSION: We identified that sexual behaviors and risk behaviors were high and changing during pregnancy and postpartum periods, presenting challenges to primary and secondary HIV prevention efforts, including PrEP delivery to pregnant and breastfeeding women.