Longitudinal Trajectories of Antiretroviral Treatment Adherence and Associations With Durable Viral Suppression Among Adolescents Living With HIV in South Africa.

BACKGROUND: Compared with other age groups, adolescents living with HIV (ALHIV) are estimated to have lower levels of adherence to antiretroviral treatment. Despite this, we lack evidence on adolescents' adherence patterns over time to inform the customization of intervention strategies. SETTING: Eastern Cape province, South Africa. METHODS: We analyzed data from a cohort of ALHIV (N = 1046, aged 10-19 years at baseline) recruited from 53 public health facilities. The cohort comprised 3 waves of data collected between 2014 and 2018 and routine viral load data from the National Institute for Communicable Disease data warehouse (2014-2019). Durable viral suppression was defined as having suppressed viral load (<1000 copies/mL) at ≥2 consecutive study waves. Group-based multitrajectory model was used to identify adherence trajectories using 5 indicators of self-reported adherence. Logistic regression modeling evaluated the associations between adherence trajectories and durable viral suppression. RESULTS: Overall, 933 ALHIV (89.2%) completed all 3 study waves (55.1% female, mean age: 13.6 years at baseline). Four adherence trajectories were identified, namely, "consistent adherence" (49.8%), "low start and increasing" (20.8%), "gradually decreasing" (23.5%), and "low and decreasing" (5.9%). Adolescents experiencing inconsistent adherence trajectories were more likely to be older, live in rural areas, and have sexually acquired HIV. Compared with the consistent adherence trajectory, the odds of durable viral suppression were lower among adolescents in the low start and increasing (adjusted odds ratio [aOR]: 0.62, 95% CI: 0.41 to 0.95), gradually decreasing (aOR: 0.40, 95% CI: 0.27 to 0.59), and the low and decreasing adherence (aOR: 0.25, 95% CI: 0.10 to 0.62) trajectories. CONCLUSIONS: Adherence to antiretroviral treatment remains a challenge among ALHIV in South Africa. Identifying adolescents at risk of nonadherence, based on their adherence trajectories may inform the tailoring of adolescent-friendly support strategies.

Healthcare provisions associated with multiple HIV-related outcomes among adolescent girls and young women living with HIV in South Africa: a cross-sectional study.

INTRODUCTION: Adolescent girls and young women (AGYW) living with HIV experience poor HIV outcomes and high rates of unintended pregnancy. Little is known about which healthcare provisions can optimize their HIV-related outcomes, particularly among AGYW mothers. METHODS: Eligible 12- to 24-year-old AGYW living with HIV from 61 health facilities in a South African district completed a survey in 2018-2019 (90% recruited). Analysing surveys and medical records from n = 774 participants, we investigated associations of multiple HIV-related outcomes (past-week adherence, consistent clinic attendance, uninterrupted treatment, no tuberculosis [TB] and viral suppression) with seven healthcare provisions: no antiretroviral therapy (ART) stockouts, kind and respectful providers, support groups, short travel time, short waiting time, confidentiality, and safe and affordable facilities. Further, we compared HIV-related outcomes and healthcare provisions between mothers (n = 336) and nulliparous participants (n = 438). Analyses used multivariable regression models, accounting for multiple outcomes. RESULTS: HIV-related outcomes were poor, especially among mothers. In multivariable analyses, two healthcare provisions were "accelerators," associated with multiple improved outcomes, with similar results among mothers. Safe and affordable facilities, and kind and respectful staff were associated with higher predicted probabilities of HIV-related outcomes (p<0.001): past-week adherence (62% when neither accelerator was reported to 87% with both accelerators reported), clinic attendance (71%-89%), uninterrupted ART treatment (57%-85%), no TB symptoms (49%-70%) and viral suppression (60%-77%). CONCLUSIONS: Accessible and adolescent-responsive healthcare is critical to improving HIV-related outcomes, reducing morbidity, mortality and onward HIV transmission among AGYW. Combining these provisions can maximize benefits, especially for AGYW mothers.

Identifying Adolescents at Highest Risk of ART Non-adherence, Using the World Health Organization-Endorsed HEADSS and HEADSS+ Checklists.

Brief tools are necessary to identify adolescents at greatest risk for ART non-adherence. From the WHO's HEADSS/HEADSS+ adolescent wellbeing checklists, we identify constructs strongly associated with non-adherence (validated with viral load). We conducted interviews and collected clinical records from a 3-year cohort of 1046 adolescents living with HIV from 52 South African government facilities. We used least absolute shrinkage and selection operator variable selection approach with a generalized linear mixed model. HEADSS constructs most predictive were: violence exposure (aOR 1.97, CI 1.61; 2.42, p < 0.001), depression (aOR 1.71, CI 1.42; 2.07, p < 0.001) and being sexually active (aOR 1.80, CI 1.41; 2.28, p < 0.001). Risk of non-adherence rose from 20.4% with none, to 55.6% with all three. HEADSS+ constructs were: medication side effects (aOR 2.27, CI 1.82; 2.81, p < 0.001), low social support (aOR 1.97, CI 1.60; 2.43, p < 0.001) and non-disclosure to parents (aOR 2.53, CI 1.91; 3.53, p < 0.001). Risk of non-adherence rose from 21.6% with none, to 71.8% with all three. Screening within established checklists can improve identification of adolescents needing increased support. Adolescent HIV services need to include side-effect management, violence prevention, mental health and sexual and reproductive health.

Exploring Self-reported Adherence Measures to Screen for Elevated HIV Viral Load in Adolescents: A South African Cohort Study.

The timely identification of ART non-adherence among adolescents living with HIV presents a significant challenge, particularly in resource-limited settings where virologic monitoring is suboptimal. Using South African adolescent cohort data (N = 933, mean age 13.6 ± 2.89 years, 55.1% female, follow-up = 2014-2018), we examined the association between elevated viral load (VL ≥ 1000 copies/mL) and seven self-reported adherence measures on missed doses, and clinic appointments -with varying recall timeframes. The best performing measures, which were significantly associated with elevated viral load in covariate-adjusted models are: any missed dose -past 3 days (sensitivity = 91.6% [95%CI: 90.3-92.8], positive predictive value (PPV) = 78.8% [95%CI: 77.2-80.4]), -past week (sensitivity = 87% [95%CI: 85.4-88.6], PPV = 78.2% [95%CI: 76.5-79.9]), -past month (sensitivity = 79.5% [95%CI: 77.5-81.4], PPV = 78.2% [95%CI: 76.4-79.9]), any past-month days missed (sensitivity = 86.7% [95%CI: 85.1-88.3], PPV = 77.9% [95%CI:76.2-79.6]), and any missed clinic appointment (sensitivity = 88.3% [95%CI: 86.8-89.8], PPV = 78.4% [95%CI: 76.8-79.9]). Combining the three best performing measures missed dose -past 3 days, -past week, and any past-year missed clinic appointment increased sensitivity to 96.4% while maintaining a PPV of about 78%. The discriminatory power of simple and easy-to-administer self-reported adherence measures in detecting elevated viral load warrants consideration in resource-limited settings and may contribute to the aims of the new Global Alliance to End AIDS in children and adolescents by 2030.

Mode of HIV acquisition among adolescents living with HIV in resource-limited settings: A data-driven approach from South Africa.

Adolescents living with HIV (ALHIV) face unique treatment and care challenges which may differ by how they acquired HIV, whether vertically (in-utero, perinatal or postnatal exposure during breastfeeding) or sexually (sexual exposure). Distinguishing and documenting the mode of HIV acquisition (MOHA) is crucial to further research on the different needs and outcomes for ALHIV and to tailor HIV services to their needs. Age-based cut-offs have been used to attribute MOHA but have not been validated. We analysed data from a three-wave cohort of n = 1107 ALHIV part of a longitudinal study in South Africa. Age-based MOHA was allocated using age at ART initiation, validated against a logic-tree model based on literature-hypothesised factors: self-reported HIV, sexual, and family history. After testing six ART initiation age cut-offs (10 to 15 years old), we determined the optimal MOHA cut-off age by calculating the sensitivity and specificity for each cut-off, measured against the final logic-tree allocation. Following validation using this longitudinal study, the methodology is extended to 214 additional third-wave participants-adolescent girls and young women living with HIV who became mothers before the age of 20. Finally, descriptive statistics of the final allocations are presented. Among the 1,063 (96.0%) cohort study participants classified, 68.7% acquired HIV vertically, following validation. ART initiation before cut-off age 10 had the highest sensitivity (58.9%) but cut-off age 12 had the largest area under the curve (AUC) (0.712). Among the additional young mothers living with HIV, 95.3% were estimated to have acquired it sexually, following the same algorithm. For this group, while cut-off ages 10 to 12 had the highest sensitivity (92.2%), age 14 had the highest AUC (0.703). ART initiation before 10 years old is strongly associated with vertical HIV acquisition. Therefore, a cut-off age of 10 would remain the recommendation in LMIC regions with similar epidemiology as South Africa for determining MOHA in research and clinic settings.

Impacts of intimate partner violence and sexual abuse on antiretroviral adherence among adolescents living with HIV in South Africa.

OBJECTIVE: We are failing to reach 95-95-95 for adolescents living with HIV (ALHIV). Sexual abuse and intimate partner violence (IPV) may impact antiretroviral therapy (ART) adherence, with high rates of 17.4 and 29.7%, respectively, across the southern sub-Saharan African region. However, evidence on their associations with adolescent ART adherence remains limited, with only three cross-sectional studies globally. DESIGN: A prospective cohort of ALHIV (sample N = 980, 55% female individuals, baseline mean age 13.6 years) were recruited from 53 health facilities in South Africa's Eastern Cape Province and responded to a structured questionnaire at 18-month and 36-month follow-up (2015-2016, 2017-2018). METHODS: A repeated-measures random effects model assessed multivariable associations of self-reported sexual abuse and IPV with past-week ART adherence, controlling for individual, socioeconomic, and HIV-related factors. Past-week adherence was defined based on currently taking ART and not having missed any doses in the past 7 days (including weekends). We further fitted a moderation model by sex. RESULTS: Fifty-one percent of adolescents reported consistent ART adherence at both time points. Exposure to IPV was associated with lower odds of self-reported ART adherence (aOR 0.39, 95% CI 0.21-0.72, P = 0.003), as was sexual abuse (aOR 0.54, 95% CI 0.29-0.99, P = 0.048). The marginal predicted probability of ART adherence for adolescents with no exposure to either IPV or sexual abuse was 72% (95% CI 70-74%) compared with 38% (95% CI 20-56%) for adolescents with exposure to both IPV and sexual abuse. Moderation results showed similar associations between sexual violence and ART adherence by sex. CONCLUSION: Sexual violence prevention and postviolence care may be essential components of supporting adolescent ART adherence. Integration of HIV and violence prevention services will require accessible services and simple referral systems.

Factors Associated with Preferences for Long-Acting Injectable Antiretroviral Therapy Among Adolescents and Young People Living with HIV in South Africa.

Long-acting injectable anti-retroviral therapy (LAART) may overcome barriers to long-term adherence and improve the survival of adolescents and young people living with HIV (AYLHIV). Research on the acceptability of LAART for this age-group is limited. We asked 953 AYLHIV about their preferred (theoretical) ART mode of delivery (pill, injectable, or other) in 2017-2018, before LAART was available or known to AYLHIV in South Africa. One in eight (12%) AYLHIV preferred LAART over single or multiple pill regimens. In multivariate analyses, six factors were associated with LAART preference: medication stock-outs (aOR = 2.56, 95% CI 1.40-4.68, p = 0.002), experiencing side-effects (aOR = 1.84, 95% CI 1.15-2.97, p = 0.012), pill-burden (aOR = 1.88, 95% CI 1.20-2.94, p = 0.006), past-year treatment changes (aOR = 1.63, 95% CI 1.06-2.51, p = 0.025), any HIV stigma (aOR = 2.22, 95% CI 1.39-3.53, p ≤ 0.001) and recent ART initiation (aOR = 2.02, 95% CI 1.09-3.74, p = 0.025). In marginal effects modelling, 66% of adolescents who experienced all factors were likely to prefer LAART, highlighting the potential high acceptability of LAART among adolescents and young people living with HIV struggling to adhere and have good HIV treatment outcomes. Adolescent boys who reported high ART pill burden were more likely to prefer LAART than their female peers in moderation analyses, suggesting that LAART may be particularly important to improve treatment outcomes among male AYLHIV as they become older. Adding LAART to existing treatment options for AYLHIV, particularly higher risk groups, would support AYLHIV to attain and sustain viral suppression-the third 95, and reduce their risk of AIDS-related mortality.

RESUMEN: La terapia antirretroviral inyectable de acción prolongada (TAR LA) puede superar las barreras a la adherencia y mejorar la supervivencia de los adolescentes y jóvenes que viven con el VIH (AJVVIH). La investigación sobre la aceptabilidad del TAR LA para este grupo de edad es limitada. Preguntamos a 953 AJVVIH sobre su modo preferido (teórico) de administración de ART (píldora, inyectable u otro) en 2017­2018, antes de que TAR LA estuviera disponible o fuera conocido por los AJVVIH en Sudáfrica. Uno de cada ocho (12%) AJVVIH prefirió TAR LA sobre los regímenes de píldoras simples o múltiples. En los análisis multivariantes, seis factores se asociaron con la preferencia de TAR LA: agotamiento de la medicación (odd ratio ajustada [ORa] = 2,56, IC95% 1,40­4,68 p = 0,002), experimentar efectos secundarios (ORa = 1,84, IC95% 1,15­2,97 p = 0,012), carga de píldoras (ORa = 1. 88, IC95% 1,20­2,94 p = 0,006), cambios de tratamiento en el último año (ORa = 1,63, IC95% 1,06­2,51 p = 0,025), cualquier estigma del VIH (ORa = 2,22, IC95% 1,39­3,53 p ≤ 0,001) y el inicio reciente del TAR (ORa = 2,02, IC95% 1,09­3,74 p = 0,025). En la modelización de efectos marginales, el 66% de los adolescentes que experimentaron todos los factores eran propensos a preferir la TAR LA, lo que pone de relieve la alta aceptabilidad potencial de la TAR LA entre los adolescentes y los jóvenes que viven con el VIH que luchan por adherirse y tener buenos resultados en el tratamiento del VIH. Los adolescentes varones que informaron de una alta carga de píldoras para el tratamiento antirretroviral eran más propensos a preferir la TAR LA que sus pares mujeres en los análisis de moderación, lo que sugiere que la TAR LA puede ser particularmente importante para mejorar los resultados del tratamiento entre los hombres que viven con el VIH a medida que crecen. La adición de la TAR LA a las opciones de tratamiento existentes para las personas que viven con el VIH, en particular los grupos de mayor riesgo, ayudaría a las personas que viven con el VIH a alcanzar y mantener la supresión vírica -el tercer 95- y a reducir el riesgo de mortalidad relacionada con el sida.

The development of children born to young mothers with no, first- or second-generation HIV acquisition in the Eastern Cape province, South Africa: a cross-sectional study.

BACKGROUND: The intergenerational effects of HIV require long-term investigation. We compared developmental outcomes of different generations impacted by HIV-children of mothers not living with HIV, the 'second generation' (ie, with recently infected mothers) and the 'third generation' (ie, children of perinatally infected mothers). METHODS: A cross-sectional community sample of N=1015 young mothers (12-25 years) and their first children (2-68 months, 48.2% female), from South Africa's Eastern Cape Province. 71.3% (n=724) of children were born to mothers not living with HIV; 2.7% (n=27; 1 living with HIV) were third-generation and 26.0% (n=264; 11 living with HIV) second-generation children. Child scores on the Mullen Scales of Early Learning (MSEL), the WHO Ten Questions Screen for Disability and maternal demographics were compared between groups using χ2 tests and univariate approach, analysis of variance analysis. Hierarchical linear regressions investigated predictive effects of familial HIV infection patterns on child MSEL composite scores, controlling for demographic and family environment variables. RESULTS: Second-generation children performed poorer on gross (M=47.0, SD=13.1) and fine motor functioning (M=41.4, SD=15.2) and the MSEL composite score (M=90.6, SD=23.0) than children with non-infected mothers (gross motor: M=50.4, SD=12.3; fine motor: M=44.4, SD=14.1; composite score: M=94.1, SD=20.7). The third generation performed at similar levels to non-exposed children (gross motor: M=52.4, SD=16.1; fine motor: M=44.3, SD=16.1, composite score: M=94.7, SD=22.2), though analyses were underpowered for definite conclusions. Hierarchical regression analyses suggest marginal predictive effects of being second-generation child compared with having a mother not living with HIV (B=-3.3, 95% CI=-6.8 to 0 .1) on MSEL total scores, and non-significant predictive effects of being a third-generation child (B=1.1, 5% CI=-7.5 to 9.7) when controlling for covariates. No group differences were found for disability rates (26.9% third generation, 27.7% second generation, 26.2% non-exposed; χ2=0.02, p=0.90). CONCLUSION: Recently infected mothers and their children may struggle due to the disruptiveness of new HIV diagnoses and incomplete access to care/support during pregnancy and early motherhood. Long-standing familial HIV infection may facilitate care pathways and coping, explaining similar cognitive development among not exposed and third-generation children. Targeted intervention and fast-tracking into services may improve maternal mental health and socioeconomic support.

Economic Well-being and Associated Mediating Pathways to Improved Antiretroviral Therapy Adherence Among Adolescents Living With HIV: A Prospective Cohort Study in South Africa.

BACKGROUND: Adolescents living with HIV exhibit lower levels of adherence to antiretroviral therapy (ART) than other age groups. Poverty is a key barrier to ART adherence. This study aims at understanding how alleviating poverty through structural and internal pathways can help increase ART adherence among adolescents. SETTING: Eastern Cape province, South Africa. METHODS: One thousand forty-six adolescents living with HIV were recruited from 53 public health care facilities and interviewed at 3 data collection waves with a retention rate of 89% and a mortality rate of 3%. Data were collected by face-to-face, device-assisted interviews. Hybrid probit regressions and a structural equation path analysis were used to estimate the association between poverty reduction (increased access to basic necessities) and the pathways by which it could improve ART adherence. RESULTS: Self-reported ART adherence ranged from an average of 66% (n = 615) at baseline to 75% (n = 700) in the last wave. Within-person and between-person improvements in economic well-being were associated with significant increases in adolescent ART adherence. On average, adolescents with access to 3 additional basic needs experienced a 4 percentage-point increase in the probability of ART adherence. Structural pathways to improved ART adherence included participants having enough money to travel to the clinic and sufficient food to eat when taking medication. Internal pathways included improved psychological well-being and reduced internalized HIV stigma. CONCLUSION: Poverty reduction programs such as HIV-sensitive social protection can address structural and psychological pathways to increase ART adherence among economically disadvantaged adolescents by incentivizing demand-side interventions and the provision of quality essential services.

From surviving to thriving: integrating mental health care into HIV, community, and family services for adolescents living with HIV.

Adolescents are a crucial generation, with the potential to bring future social and economic success for themselves and their countries. More than 90% of adolescents living with HIV reside in sub-Saharan Africa, where their mental health is set against a background of poverty, familial stress, service gaps, and an HIV epidemic that is now intertwined with the COVID-19 pandemic. In this Series paper, we review systematic reviews, randomised trials, and cohort studies of adolescents living with and affected by HIV. We provide a detailed overview of mental health provision and collate evidence for future approaches. We find that the mental health burden for adolescents living with HIV is high, contributing to low quality of life and challenges with adherence to antiretroviral therapy. Mental health provision is scarce, infrastructure and skilled providers are missing, and leadership is needed. Evidence of effective interventions is emerging, including specific provisions for mental health (eg, cognitive behavioural therapy, problem-solving, mindfulness, and parenting programmes) and broader provisions to prevent drivers of poor mental health (eg, social protection and violence prevention). We provide evidence of longitudinal associations between unconditional government grants and improved mental health. Combinations of economic and social interventions (known as cash plus care) could increase mental health benefits. Scalable delivery models include task sharing, primary care integration, strengthening families, and a pyramid of provision that differentiates between levels of need, from prevention to the care of severe disorders. A turning point has now been reached, from which complacency cannot persist. We conclude that there is substantial need, available frameworks, and a growing evidence base for action while infrastructure and skill acquisition is built.

Predictors and consequences of HIV status disclosure to adolescents living with HIV in Eastern Cape, South Africa: a prospective cohort study.

INTRODUCTION: The World Health Organization recommends full disclosure of HIV-positive status to adolescents who acquired HIV perinatally (APHIV) by age 12. However, even among adolescents (aged 10-19) already on antiretroviral therapy (ART), disclosure rates are low. Caregivers often report the child being too young and fear of disclosure worsening adolescents' mental health as reasons for non-disclosure. We aimed to identify the predictors of disclosure and the association of disclosure with adherence, viral suppression and mental health outcomes among adolescents in sub-Saharan Africa. METHODS: Analyses included three rounds (2014-2018) of data collected among a closed cohort of adolescents living with HIV in Eastern Cape, South Africa. We used logistic regression with respondent random-effects to identify factors associated with disclosure, and assess differences in ART adherence, viral suppression and mental health symptoms between adolescents by disclosure status. We also explored differences in the change in mental health symptoms and adherence between study rounds and disclosure groups with logistic regression. RESULTS: Eight hundred and thirteen APHIV were interviewed at baseline, of whom 769 (94.6%) and 729 (89.7%) were interviewed at the second and third rounds, respectively. The proportion aware of their HIV-positive status increased from 63.1% at the first round to 85.5% by the third round. Older age (adjusted odds ratio [aOR]: 1.27; 1.08-1.48) and living in an urban location (aOR: 2.85; 1.72-4.73) were associated with disclosure between interviews. There was no association between awareness of HIV-positive status and ART adherence, viral suppression or mental health symptoms among all APHIV interviewed. However, among APHIV not aware of their status at baseline, adherence decreased at the second round among those who were disclosed to (N = 131) and increased among those not disclosed to (N = 151) (interaction aOR: 0.39; 0.19-0.80). There was no significant difference in the change in mental health symptoms between study rounds and disclosure groups. CONCLUSIONS: Awareness of HIV-positive status was not associated with higher rates of mental health symptoms, or lower rates of viral suppression among adolescents. Disclosure was not associated with worse mental health. These findings support the recommendation for timely disclosure to APHIV; however, adherence support post-disclosure is important.

Past and current status of adolescents living with HIV in South Africa, 2005-2017.

OBJECTIVES: This paper reports HIV prevalence, incidence, progress towards the UNAIDS (90-90-90) targets, and HIV drug resistance among adolescents living with HIV in South Africa. We conducted secondary analyses using data extracted from the South African national HIV prevalence surveys (2005-2017). Analyses were stratified by sex and age (10-14 and 15-19-years), presenting weighted descriptive statistics, and realised totals. RESULTS: HIV prevalence increased from 3.0% in 2012 to 3.7% in 2017, translating to 360 582 (95% CI 302 021-419 144) HIV positive adolescents in 2017. Female adolescents bear a disproportionate HIV burden of 5.6% prevalence versus 0.7% for males. HIV incidence remained relatively stable. For the UNAIDS 90-90-90 targets, approximately 62.3% of adolescents knew their HIV status, 65.4% of whom were on antiretroviral therapy, and of these 78.1% on antiretroviral therapy had attained viral load suppression. There are knowledge gaps pertaining to the magnitude of perinatal infections and postnatal infections, and socio-behavioural risk factors for HIV transmission among adolescents in South Africa. There is still a need for focussed interventions targeting adolescent (1) gender disparities in HIV risk (2) screening for HIV, (3) sustained access and adherence to antiretroviral therapy and (3) retention in care to maintain viral load suppression.

Adolescent Motherhood and HIV in South Africa: Examining Prevalence of Common Mental Disorder.

The mental health of adolescents (10-19 years) remains an overlooked global health issue, particularly within the context of syndemic conditions such as HIV and pregnancy. Rates of pregnancy and HIV among adolescents within South Africa are some of the highest in the world. Experiencing pregnancy and living with HIV during adolescence have both been found to be associated with poor mental health within separate explorations. Yet, examinations of mental health among adolescents living with HIV who have experienced pregnancy/parenthood remain absent from the literature. As such, there exists no evidence-based policy or programming relating to mental health for this group. These analyses aim to identify the prevalence of probable common mental disorder among adolescent mothers and, among adolescents experiencing the syndemic of motherhood and HIV. Analyses utilise data from interviews undertaken with 723 female adolescents drawn from a prospective longitudinal cohort study of adolescents living with HIV (n = 1059) and a comparison group of adolescents without HIV (n = 467) undertaken within the Eastern Cape Province, South Africa. Detailed study questionnaires included validated and study specific measures relating to HIV, adolescent motherhood, and mental health. Four self-reported measures of mental health (depressive, anxiety, posttraumatic stress, and suicidality symptomology) were used to explore the concept of likely common mental disorder and mental health comorbidities (experiencing two or more common mental disorders concurrently). Chi-square tests (Fisher's exact test, where appropriate) and Kruskal Wallis tests were used to assess differences in sample characteristics (inclusive of mental health status) according to HIV status and motherhood status. Logistic regression models were used to explore the cross-sectional associations between combined motherhood and HIV status and, likely common mental disorder/mental health comorbidities. 70.5% of participants were living with HIV and 15.2% were mothers. 8.4% were mothers living with HIV. A tenth (10.9%) of the sample were classified as reporting a probable common mental disorder and 2.8% as experiencing likely mental health comorbidities. Three core findings emerge: (1) poor mental health was elevated among adolescent mothers compared to never pregnant adolescents (measures of likely common mental disorder, mental health comorbidities, depressive, anxiety and suicidality symptoms), (2) prevalence of probable common mental disorder was highest among mothers living with HIV (23.0%) compared to other groups (Range:8.5-12.8%; Χ2 = 12.54, p = 0.006) and, (3) prevalence of probable mental health comorbidities was higher among mothers, regardless of HIV status (HIV & motherhood = 8.2%, No HIV & motherhood = 8.2%, Χ2 = 14.5, p = 0.002). Results identify higher mental health burden among adolescent mothers compared to never-pregnant adolescents, an increased prevalence of mental health burden among adolescent mothers living with HIV compared to other groups, and an elevated prevalence of mental health comorbidities among adolescent mothers irrespective of HIV status. These findings address a critical evidence gap, highlighting the commonality of mental health burden within the context of adolescent motherhood and HIV within South Africa as well as the urgent need for support and further research to ensure effective evidence-based programming is made available for this group. Existing antenatal, postnatal, and HIV care may provide an opportunity for mental health screening, monitoring, and referral.

Predictors of secondary HIV transmission risk in a cohort of adolescents living with HIV in South Africa.

OBJECTIVE: Preventing secondary HIV transmission from adolescents and young people living with HIV (AYPLHIV) to their partners and children is critical to interrupting the HIV infection cycle in sub-Saharan Africa. We investigated predictors of secondary HIV transmission risk (past-year sexual risk combined with past-year viremia) among AYPLHIV in South Africa. DESIGN: A prospective cohort of AYLPHIV in South Africa recruited n = 1046 participants in 2014-2015, 93.6% of whom were followed up in 2016-2017 (1.5% mortality). Questionnaires used validated scales where available and biomarkers were extracted from n = 67 health facilities. METHODS: Multivariate logistic regressions tested baseline factors associated with secondary HIV transmission risk, controlling for covariates, with marginal effect modelling combinations. RESULTS: About 14.2% of AYPLHIV reported high secondary HIV transmission risk. High-risk AYPLHIV were more likely to be sexually infected [adjusted odds ratio (aOR) 2.79, 95% confidence interval (95% CI) 1.66-4.68, P < 0.001], and report hunger (aOR 1.93, 95% CI 1.18-3.14, P = 0.008) and substance use (aOR 2.19, 95% CI 1.19-4.02, P = 0.012). They were more likely to be in power-inequitable relationships (aOR 1.77, 95% CI 1.08-2.92, P = 0.025) and be parents (aOR 4.30, 95% CI 2.16-8.57, P < 0.001). Adolescents reporting none of these factors had a 4% probability of secondary transmission risk, rising to 89% probability with all five identified factors. Older age and early sexual debut were also strongly associated with a higher risk of secondary HIV transmission. CONCLUSION: It is essential to identify and support AYPLHIV at a high risk of secondary transmission. Screening for factors such as mode of infection and parenthood during routine healthcare visits could help identify and provide resources to the most at-risk adolescents.

Uncovering ART adherence inconsistencies: An assessment of sustained adherence among adolescents in South Africa.

INTRODUCTION: Antiretroviral treatment (ART) adherence rates are lower among adolescents living with HIV (ALHIV) than among adults and children, but more evidence is needed on long-term sustained ART adherence among ALHIV. This study assesses rates of sustained ART adherence in a cohort of adolescents in South Africa. METHODS: A prospective cohort of adolescents (10-19 years) living with HIV (baseline sample N = 1 046, 55% female, mean age 13.6) in the Eastern Cape Province in South Africa were interviewed at baseline (2014-15) and followed-up twice (2015-16, 2017-18). All adolescents ever initiated on treatment in 52 government health facilities were traced (with 90% uptake, 94% retention at Wave 2, and 97% retention at Wave 3, 3.4% mortality) and their clinic records were extracted where available. We investigate sustained ART adherence among adolescents interviewed at all three waves of data collection (N = 933). To quantify adherence at each study wave, we used self-reported past-week adherence (including weekdays and weekends). Self-reported adherence was validated using HIV-1 RNA viral load (>50 copies/mL cut-off) reported in clinic records, in a random-intercept logistic regression. RESULTS AND DISCUSSION: At baseline, approximately 66% (N = 615) of adolescents reported past-week ART adherence, and of these 45.3% reported adherence at both baseline and follow-up. Only 37.1% of the sample reported sustained past-week ART adherence over the three waves of the study. Most adolescents (N = 587, 62.9%) report inconsistent adherence across time (including 6.4% disengaged from care). Older (P = 0.007) and adolescents with horizontally acquired HIV (P = 0.002) were more likely to report inconsistent adherence across time. Controlling for socio-demographic characteristics, past-week adherence was associated with non-detectable viral load (aOR 1.72, 95%CI 1.14-2.59, P = 0.009). Overall, of the adolescents with viral load measurements at study Wave 1 and Wave 2, 50.6% maintained undetectable viral load for the preceding year. CONCLUSIONS: Adolescents living with HIV reported very low rates of sustained ART adherence. Adherence reported at a single time may mask high rates of variability in adherence over time. These findings highlight the urgent need for enhanced and effective interventions to assist ALHIV with ART adherence through the challenging years of adolescence.

Clinic and care: associations with adolescent antiretroviral therapy adherence in a prospective cohort in South Africa.

OBJECTIVE: Adolescent antiretroviral treatment (ART) adherence remains critically low. We lack research testing protective factors across both clinic and care environments. DESIGN: A prospective cohort of adolescents living with HIV (sample n = 969, 55% girls, baseline mean age 13.6) in the Eastern Cape Province in South Africa were interviewed at baseline and 18-month follow-up (2014-2015, 2015-2016). We traced all adolescents ever initiated on treatment in 52 government health facilities (90% uptake, 93% 18-month retention, 1.2% mortality). METHODS: Clinical records were collected; standardized questionnaires were administered by trained data collectors in adolescents' language of choice. Probit within-between regressions and average adjusted probability calculations were used to examine associations of caregiving and clinic factors with adherence, controlling for household structure, socioeconomic and HIV factors. RESULTS: Past-week ART adherence was 66% (baseline), 65% (follow-up), validated against viral load in subsample. Within-individual changes in three factors were associated with improved adherence: no physical and emotional violence (12.1 percentage points increase in adjusted probability of adherence, P < 0.001), improvement in perceived healthcare confidentiality (7.1 percentage points, P < 0.04) and shorter travel time to the clinic (13.7 percentage points, P < 0.02). In combination, improvement in violence prevention, travel time and confidentiality were associated with 81% probability of ART adherence, compared with 47% with a worsening in all three. CONCLUSION: Adolescents living with HIV need to be safe at home and feel safe from stigma in an accessible clinic. This will require active collaboration between health and child protection systems, and utilization of effective violence prevention interventions.

Bullying and ART Nonadherence Among South African ALHIV: Effects, Risks, and Protective Factors.

BACKGROUND: Identifying risk and protective factors for adolescent antiretroviral therapy (ART) adherence is a public health priority, given high HIV-related mortality in this population. An area that merits further investigation is the relationship between bullying victimization, mental health problems, and ART nonadherence among adolescents living with HIV (ALHIV). However, no known studies assess effects of bullying on adolescent nonadherence or risk and protective factors that could moderate this relationship. SETTING: This study investigates (1) the direct longitudinal relationship between bullying exposure and ART nonadherence, and the indirect relationship via psychological distress, and (2) potential risk and modifiable protective factors moderating these pathways, among vertically and horizontally infected ALHIV who initiated treatment across 53 public health care facilities in a South African health district. METHODS: Survey data were collected at 2 time points, between 2014 and 2017, with 1046 ALHIV (94% retention). Various mediation and moderated mediation models were run as part of a staged analysis approach. RESULTS: A significant longitudinal relationship was found between bullying victimization and nonadherence, operating indirectly through psychological distress [B = 0.07; 95% confidence interval (CI): (0.03 to 0.13)]. Moderation analyses indicated that older adolescents exposed to bullying are more at risk of nonadherence [B = 0.52; 95% CI: (0.07 to 0.97) P < 0.05], and parental monitoring is a potential protective factor buffering indirect effects of bullying on nonadherence [B = -0.22; 95% CI: (-0.42 to -0.02) P < 0.05]. CONCLUSIONS: These findings underscore the importance of interventions that address bullying and psychological distress, and strengthen parental monitoring, particularly among older ALHIV.

Violence prevention accelerators for children and adolescents in South Africa: A path analysis using two pooled cohorts.

BACKGROUND: The INSPIRE framework was developed by 10 global agencies as the first global package for preventing and responding to violence against children. The framework includes seven complementary strategies. Delivering all seven strategies is a challenge in resource-limited contexts. Consequently, governments are requesting additional evidence to inform which 'accelerator' provisions can simultaneously reduce multiple types of violence against children. METHODS AND FINDINGS: We pooled data from two prospective South African adolescent cohorts including Young Carers (2010-2012) and Mzantsi Wakho (2014-2017). The combined sample size was 5,034 adolescents. Each cohort measured six self-reported violence outcomes (sexual abuse, transactional sexual exploitation, physical abuse, emotional abuse, community violence victimisation, and youth lawbreaking) and seven self-reported INSPIRE-aligned protective factors (positive parenting, parental monitoring and supervision, food security at home, basic economic security at home, free schooling, free school meals, and abuse response services). Associations between hypothesised protective factors and violence outcomes were estimated jointly in a sex-stratified multivariate path model, controlling for baseline outcomes and socio-demographics and correcting for multiple-hypothesis testing using the Benjamini-Hochberg procedure. We calculated adjusted probability estimates conditional on the presence of no, one, or all protective factors significantly associated with reduced odds of at least three forms of violence in the path model. Adjusted risk differences (ARDs) and adjusted risk ratios (ARRs) with 95% confidence intervals (CIs) were also calculated. The sample mean age was 13.54 years, and 56.62% were female. There was 4% loss to follow-up. Positive parenting, parental monitoring and supervision, and food security at home were each associated with lower odds of three or more violence outcomes (p < 0.05). For girls, the adjusted probability of violence outcomes was estimated to be lower if all three of these factors were present, as compared to none of them: sexual abuse, 5.38% and 1.64% (ARD: -3.74% points, 95% CI -5.31 to -2.16, p < 0.001); transactional sexual exploitation, 10.07% and 4.84% (ARD: -5.23% points, 95% CI -7.26 to -3.20, p < 0.001); physical abuse, 38.58% and 23.85% (ARD: -14.72% points, 95% CI -19.11 to -10.33, p < 0.001); emotional abuse, 25.39% and 12.98% (ARD: -12.41% points, 95% CI -16.00 to -8.83, p < 0.001); community violence victimisation, 36.25% and 28.37% (ARD: -7.87% points, 95% CI -11.98 to -3.76, p < 0.001); and youth lawbreaking, 18.90% and 11.61% (ARD: -7.30% points, 95% CI -10.50 to -4.09, p < 0.001). For boys, the adjusted probability of violence outcomes was also estimated to be lower if all three factors were present, as compared to none of them: sexual abuse, 2.39% to 1.80% (ARD: -0.59% points, 95% CI -2.24 to 1.05, p = 0.482); transactional sexual exploitation, 6.97% to 4.55% (ARD: -2.42% points, 95% CI -4.77 to -0.08, p = 0.043); physical abuse from 37.19% to 25.44% (ARD: -11.74% points, 95% CI -16.91 to -6.58, p < 0.001); emotional abuse from 23.72% to 10.72% (ARD: -13.00% points, 95% CI -17.04 to -8.95, p < 0.001); community violence victimisation from 41.28% to 35.41% (ARD: -5.87% points, 95% CI -10.98 to -0.75, p = 0.025); and youth lawbreaking from 22.44% to 14.98% (ARD -7.46% points, 95% CI -11.57 to -3.35, p < 0.001). Key limitations were risk of residual confounding and not having information on protective factors related to all seven INSPIRE strategies. CONCLUSION: In this cohort study, we found that positive and supervisory caregiving and food security at home are associated with reduced risk of multiple forms of violence against children. The presence of all three of these factors may be linked to greater risk reduction as compared to the presence of one or none of these factors. Policies promoting action on positive and supervisory caregiving and food security at home are likely to support further efficiencies in the delivery of INSPIRE.

Reproductive aspirations, contraception use and dual protection among adolescent girls and young women: the effect of motherhood and HIV status.

INTRODUCTION: There is a growing interest in adolescent motherhood and HIV among policymakers and programme implementers. To better shape services and health outcomes, we need evidence on reproductive aspirations and contraception use in this high-risk group, including the effect of motherhood and HIV status. We report data from a large survey of adolescent girls and young women conducted in a mixed rural-urban district in South Africa. METHODS: Quantitative interviews were conducted with 1712 adolescent girls and young women (ages 10 to 24): 336 adolescent mothers living with HIV (AMLHIV), 454 nulliparous adolescent girls living with HIV (ALHIV), 744 HIV-negative adolescent mothers (control adolescent mothers) and 178 HIV-negative nulliparous adolescent girls (nulliparous controls) in 2018 to 2019. Standardized questionnaires included socio-demographic measures, reproductive health and contraception experiences. Reproductive aspirations were measured as the number of children participants wanted to have. Dual protection was computed as use of both hormonal and barrier contraception or abstinence. Multivariate logistic regression and marginal effects models in STATA 15 were used to test associations between HIV status, adolescent motherhood and outcomes of reproductive aspirations, contraception use and dual protection, controlling for covariates. RESULTS AND DISCUSSION: Nearly 95% of first pregnancies were unintended. Over two-thirds of all participants wanted two or more children. Hormonal contraception, condom use and dual protection were low across all groups. In multivariate regression modelling, ALHIV were less likely to report hormonal contraception use (aOR 0.55 95% CI 0.43 to 0.70 p ≤ 0.001). In marginal effects modelling, adolescent mothers - independent of HIV status - were least likely to report condom use at last sex. Despite higher probabilities of using hormonal contraception, rates of dual protection were low: 17.1% among control adolescent mothers and 12.4% among AMLHIV. Adolescent mothers had the highest probabilities of not using any contraceptive method: 29.0% among control mothers and 23.5% among AMLHIV. CONCLUSIONS: Among adolescent girls and young women in HIV-endemic communities, reproductive aspirations and contraceptive practices affect HIV risk and infection. Tailored adolescent-responsive health services could help young women plan their pregnancies for when they are healthy and well-supported, and help interrupt the cycle of HIV transmission by supporting them to practice dual protection.