Cumulative exposure to depressive symptoms and all-cause mortality among adults living with HIV in Kenya, Nigeria, Tanzania, and Uganda.

OBJECTIVE: :We estimated the effects of cumulative exposure to depressive symptoms on risk of all-cause mortality among people living with HIV in four African countries. DESIGN: :Analysis of prospective cohort data. METHODS: :The African Cohort Study (AFRICOS) is a prospective cohort of people receiving care at twelve clinics in Kenya, Nigeria, Tanzania, and Uganda. Every six months from January 2013 to May 2020, participants underwent laboratory monitoring, structured surveys, and assessment of depressive symptom severity using the Center for Epidemiologic Studies Depression Scale (CES-D). All-cause mortality was the outcome of interest. The predictor of interest was a time-updated measure of the percentage of days lived with depression (PDD). Marginal structural Cox proportional hazards regression models were used, adjusting for potential confounders including time-varying alcohol use, drug use, and viral load. RESULTS: :Among 2520 enrolled participants, 1479 (59%) were women and the median age was 38 (interquartile range [IQR]: 32-46). At enrollment, 1438 (57%) were virally suppressed (<200 copies/mL) and 457 (18%) had CES-D ≥ 16, indicating possible depression. Across 9093 observed person-years, the median PDD was 0.7% (IQR: 0-5.9%) with 0.8 deaths per 100 person-years. Leading causes of death included cancer (18% of deaths) and accidents (14%). Models suggested that each 25% absolute increase in PDD was associated with a 69% increase in the risk of all-cause mortality (HR: 1.69; 95% CI: 1.18-2.43). CONCLUSIONS: :Cumulative exposure to depressive symptoms was substantially associated with the risk of mortality in this cohort of PLWH in Africa.

Higher rates of mental health screening of adolescents recorded after provider training using simulated patients in a Kenyan HIV clinic: results of a pilot study.

Background: Kenyan adolescent girls and young women (AGYW) experience a dual burden of HIV and common mental disorders (CMD). HIV clinics are a key entry point for AGYW in need of integrated CMD and HIV care; however, rates of screening and referral for CMDs are low. Our objective was to test an evidence-based provider training strategy, simulated patient encounters (SPEs), on CMD service delivery for AGYW in a Kenyan HIV clinic. Methods: This pilot study was conducted in a public HIV clinic in Thika, Kenya from January to November 2021. The simulated patient encounter (SPE) implementation strategy included case script development from prior qualitative work, patient actor training, and a three-day SPE training including four standardized mock clinical encounters followed by quantitative surveys assessing provider competencies for each encounter. We abstracted medical record data related to HIV and CMDs such as HIV status, reason for visit, CMD screening test performed, and counselling or referral information. We conducted an interrupted time series analysis using abstracted HIV and CMD screening rates from AGYW ages 16-25 years visiting the clinic 7 months before and 3 months after SPE training. We used generalized linear models to assess changes in CMD screening rates after training. Results: A total of 10 providers participated in the training. Competency ratings improved across four mock encounters (mean score from 8.1 to 13.7) between first and fourth encounters. We abstracted all medical records (n = 1,154) including from 888 (76%) AGYW seeking HIV treatment, 243 (21%) seeking prevention services, and 34 (3%) seeking other services. CMD screening rates increased immediately following training from 8 to 21% [relative risk (RR) = 2.57, 95% confidence interval (CI) = 1.34-4.90, p < 0.01]. The 3 months following the SPE training resulted in an 11% relative increase in CMD screening proportion compared to the 7 months pre-SPE (RR: 1.11, 95% CI: 1.04-1.17, p < 0.01). Finally, 1% of all pre-SPE screens resulted in referral versus 5% of post-SPE screens (p = 0.07). Conclusion: The SPE model is a promising implementation strategy for improving HIV provider competencies and CMD service delivery for adolescents in HIV clinics. Future research is needed to explore effects on adolescent clinical outcomes in larger trials.

PrEP uptake and early persistence among adolescent girls and young women receiving services via community and hybrid community-clinic models in Namibia.

INTRODUCTION: Adolescent girls and young women (AGYW) face barriers in accessing clinic-based HIV pre-exposure prophylaxis (PrEP) services and community-based models are a proposed alternative. Evidence from such models, however, is limited. We evaluated PrEP service coverage, uptake, and early persistence among AGYW receiving services through community and hybrid models in Namibia. METHODS: We analyzed routine data for AGYW aged 15-24 who initiated PrEP within HIV prevention programming. PrEP was delivered via three models: community-concierge (fully community-based services with individually-tailored refill locations), community-fixed (community-based initiation and refills delivered by community providers on a set schedule at fixed sites), and hybrid community-clinic (community-based initiation and referral to clinics for refills delivered by clinic providers). We examined proportions of AGYW engaged in services along a programmatic PrEP cascade, overall and by model, and assessed factors associated with PrEP uptake and early persistence (refill within 15-44 days after initiation) using multivariable generalized estimating equations. RESULTS: Over 10-months, 7593 AGYW participated in HIV prevention programming. Of these, 7516 (99.0%) received PrEP education, 6105 (81.2%) received HIV testing services, 6035 (98.9%) tested HIV-negative, and 2225 (36.9%) initiated PrEP. Of the 2047 AGYW expected for PrEP refill during the study period, 254 (12.4%) persisted with PrEP one-month after initiation. Structural and behavioral HIV risk factors including early school dropout, food insecurity, inconsistent condom use, and transactional sex were associated with PrEP uptake. AGYW who delayed starting PrEP were 2.89 times more likely to persist (95% confidence interval (CI): 1.52-5.46) and those receiving services via the community-concierge model were 8.7 times (95% CI: 5.44-13.9) more likely to persist (compared to the hybrid model). CONCLUSION: Community-based models of PrEP service delivery to AGYW can achieve high PrEP education and HIV testing coverage and moderate PrEP uptake. AGYW-centered approaches to delivering PrEP refills can promote higher persistence.

Evidencing the Impact of Web-Based Coproduction With Youth on Mental Health Research: Qualitative Findings From the MindKind Study.

BACKGROUND: Public involvement in research is a growing phenomenon as well as a condition of research funding, and it is often referred to as coproduction. Coproduction involves stakeholder contributions at every stage of research, but different processes exist. However, the impact of coproduction on research is not well understood. Web-based young people's advisory groups (YPAGs) were established as part of the MindKind study at 3 sites (India, South Africa, and the United Kingdom) to coproduce the wider research study. Each group site, led by a professional youth advisor, conducted all youth coproduction activities collaboratively with other research staff. OBJECTIVE: This study aimed to evaluate the impact of youth coproduction in the MindKind study. METHODS: To measure the impact of web-based youth coproduction on all stakeholders, the following methods were used: analysis of project documents, capturing the views of stakeholders using the Most Significant Change technique, and impact frameworks to assess the impact of youth coproduction on specific stakeholder outcomes. Data were analyzed in collaboration with researchers, advisors, and YPAG members to explore the impact of youth coproduction on research. RESULTS: The impact was recorded on 5 levels. First, at the paradigmatic level, a novel method of conducting research allowed for a widely diverse group of YPAG representations, influencing study priorities, conceptualization, and design. Second, at the infrastructural level, the YPAG and youth advisors meaningfully contributed to the dissemination of materials; infrastructural constraints of undertaking coproduction were also identified. Third, at the organizational level, coproduction necessitated implementing new communication practices, such as a web-based shared platform. This meant that materials were easily accessible to the whole team and communication streams remained consistent. Fourth, at the group level, authentic relationships developed between the YPAG members, advisors, and the rest of the team, facilitated by regular web-based contact. Finally, at the individual level, participants reported enhanced insights into mental well-being and appreciation for the opportunity to engage in research. CONCLUSIONS: This study revealed several factors that shape the creation of web-based coproduction, with clear positive outcomes for advisors, YPAG members, researchers, and other project staff. However, several challenges of coproduced research were also encountered in multiple contexts and amid pressing timelines. For systematic reporting of the impact of youth coproduction, we propose that monitoring, evaluation, and learning systems be designed and implemented early.

Young people's data governance preferences for their mental health data: MindKind Study findings from India, South Africa, and the United Kingdom.

Mobile devices offer a scalable opportunity to collect longitudinal data that facilitate advances in mental health treatment to address the burden of mental health conditions in young people. Sharing these data with the research community is critical to gaining maximal value from rich data of this nature. However, the highly personal nature of the data necessitates understanding the conditions under which young people are willing to share them. To answer this question, we developed the MindKind Study, a multinational, mixed methods study that solicits young people's preferences for how their data are governed and quantifies potential participants' willingness to join under different conditions. We employed a community-based participatory approach, involving young people as stakeholders and co-researchers. At sites in India, South Africa, and the UK, we enrolled 3575 participants ages 16-24 in the mobile app-mediated quantitative study and 143 participants in the public deliberation-based qualitative study. We found that while youth participants have strong preferences for data governance, these preferences did not translate into (un)willingness to join the smartphone-based study. Participants grappled with the risks and benefits of participation as well as their desire that the "right people" access their data. Throughout the study, we recognized young people's commitment to finding solutions and co-producing research architectures to allow for more open sharing of mental health data to accelerate and derive maximal benefit from research.

Provider perspectives on service delivery modifications to maintain access to HIV pre-exposure prophylaxis during the COVID-19 pandemic: qualitative results from a PrEP implementation project in Kenya.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) is an essential prevention strategy being scaled up for priority populations in Kenya, including for HIV serodiscordant couples. The COVID-19 pandemic posed challenges to PrEP rollout. We conducted a qualitative study of PrEP providers to understand how clinics adjusted PrEP delivery during the COVID-19 pandemic. METHODS: Since 2017, the Partners Scale-Up Project has integrated PrEP into 25 HIV clinics in Central and Western Kenya. We conducted qualitative interviews with 40 purposively sampled clinic personnel. We interviewed personnel once during the first pandemic wave (May-Aug 2020) and again after some decline in COVID-19 rates (Nov-Jan 2021). We analysed data using inductive memo-writing and summarized data by themes along the PrEP delivery cascade, guided by the Framework for Reporting Adaptation and Modifications (FRAME). RESULTS: We interviewed 27 clinical officers, five nurses, four health records and information officers, and four counsellors from Central (n = 20) and Western (n = 20) Kenya. About half (n = 19) were female, with a median age of 32 (IQR: 29-34) and 2.3 years of experience delivering PrEP (IQR: 2-3). All participants reported clinic changes in PrEP demand creation and service delivery during the pandemic. Modifications occurred during PrEP implementation and sustainment phases, were partly reactive to the pandemic and also facilitated by interim Ministry of Health guidance on PrEP delivery during COVID, and were made by PrEP delivery teams, clients and clinic managers. Commonly reported modifications included dispensing multiple-month PrEP refills, intensifying phone-based client engagement and collaborating with other HIV clinics to ensure that clients with prolonged stays in other regions could continue to access PrEP. Some clinics also adopted practices to streamline visits, such as within clinical-room PrEP dispensing, pre-packing PrEP and task-shifting. Most providers liked these changes and hoped they would continue after the pandemic subsides. CONCLUSIONS: COVID-19 served as a catalyst for PrEP delivery innovations in Kenya. HIV clinics successfully and rapidly adapted their PrEP demand creation, refill and retention strategies to promote PrEP uptake and effective use. These modified implementation strategies highlight opportunities to streamline the delivery of PrEP, as well as other HIV and chronic care services, and strengthen engagement with populations post-pandemic.

Advancing considerations of context in the evaluation and implementation of evidence-based biomedical HIV prevention interventions: a review of recent research.

PURPOSE OF REVIEW: A paradigm shift is needed in how we think about biomedical HIV prevention product effectiveness. Often, we expect randomized trial findings to be generalizable across populations and settings where products will be delivered, without consideration of key contextual drivers that could impact effectiveness. Moreover, researchers and policy-makers generally discount products with varied effect sizes across contexts, rather than explicating the drivers of these differences and using them to inform equitable product choice and delivery. We conducted a review of the recent HIV prevention research to advance considerations of context in choices of when, why, and how to implement biomedical HIV prevention products, with a particular focus on daily oral preexposure prophylaxis (PrEP) and the dapivirine vaginal ring (DPV). RECENT FINDINGS: Findings across recent studies of PrEP and DPV emphasize that products that do not work well in one context might be highly desirable in another. Key contextual drivers of PrEP and DPV effectiveness, use, and implementation include population, health system, cultural, and historical factors. We recommend conceptualization, measurement, and analysis approaches to fully understand the potential impact of context on prevention product delivery. Execution of these approaches has real-world implications for HIV prevention product choice and could prevent the field from dismissing biomedical HIV prevention products based on trial findings alone. SUMMARY: Ending the HIV epidemic will require tailored, person-centered, and equitable approaches to design, implement, and evaluate HIV prevention products which necessitates considerations of context in ongoing research and implementation.

A novel "HIV salience and Perception" scale is associated with PrEP dispensing and adherence among adolescent girls and young women in Kampala, Uganda.

Low perceived HIV risk is a barrier to effective pre-exposure prophylaxis (PrEP) use among African adolescent girls and young women (AGYW). Single-item risk perception measures are stigmatizing and alienating to AGYW and may not predict PrEP use. There is a need for a tool capturing domains of perceived HIV risk and salience that align with PrEP use among AGYW. This HIV PrEP study was conducted in Kampala, Uganda. We developed and piloted the 9-item "HIV Salience and Perception" (HPS) scale (range: 9-36); higher scores indicate beliefs of higher vulnerability to HIV. We administered the scale to Ugandan AGYW participating in an ongoing cohort study at enrollment, one, three and six months. PrEP dispensing was measured quarterly and adherence was measured daily via Wisepill (high adherence: ≥80% of expected pill bottle openings). We assessed scale performance and used generalized estimating equations to determine associations between scale score and PrEP use. Among 499 AGYW, 54.1% of our sample was ≥ 20 years (range:16-25). The median HPS score was 18 (range:8-33; α = 0.77). Higher score was associated with PrEP dispensing (aRR = 1.07 per point increase; 95% CI = 1.01-1.13; p-value = 0.02) in the overall cohort and among only those ≥ 20 years (aRR = 1.10; 95% CI = 1.03-1.19; p-value = 0.01). We did not observe an association between scale score and PrEP adherence. AGYW scoring higher on a novel HPS scale were more likely to initiate and obtain PrEP refills through 6 months. This scale may capture drivers of PrEP dispensing and could inform PrEP delivery and counseling for AGYW.

Perinatal Depressive Symptoms and Viral Non-suppression Among a Prospective Cohort of Pregnant Women Living with HIV in Nigeria, Kenya, Uganda, and Tanzania.

Depression is common during pregnancy and is associated with reduced adherence to HIV-related care, though little is known about perinatal trajectories of depression and viral suppression among women living with HIV (WLHV) in sub-Saharan Africa. We sought to assess any association between perinatal depressive symptoms and viral non-suppression among WLWH. Depressive symptomatology and viral load data were collected every 6 months from WLWH enrolled in the African Cohort Study (AFRICOS; January 2013-February 2020). Generalized estimating equations modeled associations between depressive symptoms [Center for Epidemiological Studies Depression (CES-D) ≥ 16] and viral non-suppression. Of 1722 WLWH, 248 (14.4%) had at least one pregnancy (291 total) and for 61 pregnancies (21.0%), women reported depressive symptoms (13.4% pre-conception, 7.6% pregnancy, 5.5% one-year postpartum). Depressive symptomatology was associated with increased odds of viral non-suppression (aOR 2.2; 95% CI 1.2-4.0, p = 0.011). Identification and treatment of depression among women with HIV may improve HIV outcomes for mothers.

Acceptability Assessment in HIV Prevention and Treatment Intervention and Service Delivery Research: A Systematic Review and Qualitative Analysis.

We reviewed the literature on the assessment of acceptability of HIV prevention and treatment interventions and service delivery strategies. Following PRISMA guidelines, we screened 601 studies published from 2015 to 2020 and included 217 in our review. Of 384 excluded studies, 21% were excluded because they relied on retention as the sole acceptability indicator. Of 217 included studies, only 16% were rated at our highest tier of methodological rigor. Operational definitions of acceptability varied widely and failed to comprehensively represent the suggested constructs in current acceptability frameworks. Overall, 25 studies used formal quantitative assessments (including four adapted measures used in prior studies) and six incorporated frameworks of acceptability. Findings suggest acceptability assessment in recent HIV intervention and service delivery research lacks harmonization and rigor. We offer guidelines for best practices and future research, which are timely and critical in this era of informed choice and novel options for HIV prevention and treatment.

Alignment of PrEP adherence with periods of HIV risk among adolescent girls and young women in South Africa and Zimbabwe: a secondary analysis of the HPTN 082 randomised controlled trial.

BACKGROUND: Adolescent girls and young women in southern and eastern Africa have adherence challenges with daily oral HIV pre-exposure prophylaxis (PrEP). High adherence is most important during periods of HIV risk (prevention-effective adherence). We aimed to describe HIV risk behaviour and to understand patterns in PrEP adherence during periods of risk among adolescent girls and young women from sub-Saharan Africa. METHODS: We did a secondary analysis of the HPTN 082 trial, an open-label, interventional, randomised controlled trial of sexually active adolescent girls and young women (aged 16-25 years) testing negative for HIV in Johannesburg and Cape Town, South Africa, and in Harare, Zimbabwe. The primary outcomes were high cumulative PrEP adherence, dichotomised as intracellular tenofovir diphosphate concentrations of at least 700 fmol/punch in dried blood spots at weeks 13, 26, and 52, and high recent PrEP adherence, dichotomised as plasma tenofovir concentrations of at least 40 ng/mL at weeks 13, 26, and 52, among participants who accepted PrEP. We collected data on sexual behaviour every 3 months. We categorised visits into a binary variable of any HIV risk based on condomless sex, more than one sexual partner, primary partner's HIV status and antiretroviral use, transactional sex, drug or alcohol use around sexual activity, and laboratory-diagnosed STIs. We used generalised estimating equations to evaluate associations between HIV risk (reflecting behaviour during the previous 3 months) and high cumulative and recent adherence to PrEP and any PrEP use (quantifiable drug concentrations). The trial is registered with ClinicalTrials.gov, NCT02732730. FINDINGS: Between Oct 12, 2016, and Oct 25, 2018, 451 women were recruited, and 427 participants (median age 21·0 years [IQR 19·0-22·0]) were eligible for inclusion in this analysis. The proportion of participants reporting at least one HIV risk factor decreased significantly over follow-up, from 364 (85%) participants at enrolment, 226 (60%) at week 13, and 243 (65%) at week 26, to 224 (61%) at week 52 (p<0·0001). Any HIV risk was significantly associated with high PrEP adherence, measured by both tenofovir diphosphate concentrations of at least 700 fmol/punch (adjusted relative risk 1·57 [95% CI 1·09-2·25]; p=0·014) and plasma tenofovir concentrations of at least 40 ng/mL (1·36 [1·11-1·65]; p=0·0025). Any HIV risk was also associated with quantifiable concentrations of tenofovir diphosphate (1·15 [1·03-1·29]; p=0·013) and tenofovir (1·27 [1·09-1·49]; p=0·0022). We observed significant dose-response relationships between number of HIV risk factors and PrEP drug concentrations. INTERPRETATION: The association between any HIV risk and high PrEP adherence suggests that adolescent girls and young women were able to use PrEP during periods of risk, an indicator of prevention-effective PrEP adherence. Our findings support a shift in the PrEP framework to acknowledge prevention-effective adherence practices, which might improve PrEP delivery and adherence support for adolescent girls and young women in HIV-endemic settings. FUNDING: US National Institutes of Health.

Disclosure and help-seeking behaviors related to sexual and physical violence in childhood and adolescence: Results from the Namibia Violence Against Children and Youth Survey.

BACKGROUND: Violence disclosure and help-seeking can mitigate adverse health effects associated with childhood violence, but little is known about facilitators and barriers of disclosure and help-seeking behaviors in sub-Saharan Africa. OBJECTIVE: To understand factors associated with disclosure and help-seeking to inform care. PARTICIPANTS AND SETTING: Participants aged 13-24 years old in the 2019 Namibia Violence Against Children and Youth Survey (VACS). METHODS: We assessed the prevalence of victimization, disclosure, and help-seeking and examined factors associated with violence disclosure and help-seeking, separately, by gender. RESULTS: 4211 girls and 980 boys participated in the Namibia VACS. The prevalence of childhood sexual violence differed significantly by gender (15.7% among girls, 9.8% among boys), but physical violence prevalence did not differ by gender. Among victims of sexual violence, 57.3% of girls disclosed and 10.4% sought help, compared with only 30.7% and 3.2% of boys. Among victims of physical violence, 61.1% of girls and 53.4% of boys disclosed, and 16.9% of girls and 17.7% of boys sought help. Older age, social support, and experiencing more types of violence were associated with sexual violence disclosure among boys, but none of these factors were associated with sexual violence disclosure among girls. Lower education, perpetrator type, and witnessing violence were associated with physical violence disclosure among girls, while peer support and perpetrator type were associated with physical violence disclosure among boys. CONCLUSIONS: Factors associated with childhood violence differed by gender and violence type in Namibia, highlighting a need for gender-specific violence services to facilitate violence disclosure and help-seeking.

Adaptive HIV pre-exposure prophylaxis adherence interventions for young South African women: Study protocol for a sequential multiple assignment randomized trial.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy and is recommended for populations at risk of HIV, including adolescent girls and young women (AGYW) in HIV endemic settings. However, PrEP continuation and high adherence remain challenges to its impact. Existing PrEP adherence interventions can be time- and cost-intensive. Widescale PrEP delivery will require the identification of layered PrEP support strategies for AGYW with diverse prevention needs. We describe the design of a sequential multiple assignment randomized trial (SMART) to evaluate a PrEP adherence support model using scalable, stepped interventions in AGYW in South Africa. METHODS: "PrEP SMART" is a randomized trial in Johannesburg, South Africa, enrolling AGYW who are between 18 and 25 years of age, sexually active, newly initiating PrEP, and have regular access to a mobile phone. Participants are randomized 1:1 to standard-of-care PrEP counseling with either two-way SMS or WhatsApp group adherence support. Adherence is assessed at three months using tenofovir diphosphate (TFV-DP) levels from dried blood spots collected at month 2 to categorize participants as "responders" (TFV-DP ≥500 fmol/punch) or "non-responders" (TFV-DP <500 fmol/punch). AGYW defined as 'non-responders' undergo a secondary 1:1 randomization to either quarterly drug-level feedback counseling or monthly issue-focused counseling, in addition to their first-level intervention. The primary outcome is PrEP adherence at nine months (TFV-DP ≥700 fmol/punch). We will assess the effect of our two initial interventions on TFV-DP levels among responders, assess the effect of our intensified interventions on TFV-DP levels among non-responders, and identify the optimal sequence of adherence interventions through nine months. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04038060. Registered on 30 July 2019.

Cycles of Violence Among Young Women in Namibia: Exploring the Links Between Childhood Violence and Adult Intimate Partner Violence From the Violence Against Children and Youth Survey.

Background: Violence against children is a global public health crisis and is associated with poor mental and physical health outcomes. Childhood violence may also increase the risk of subsequent violence revictimization by an intimate partner. We aimed to understand cycles of violence among adolescent girls and young women in Namibia to inform violence prevention and treatment interventions. Methods: The 2019 Namibia Violence Against Children and Youth Survey (VACS) examined the prevalence of childhood violence and intimate partner violence among 18-24 year old adolescent girls and young women (N = 2434). Using the data, we assessed the prevalence of childhood violence, defined as any physical, sexual, or emotional violence victimization prior to age 18, and estimated the prevalence of intimate partner violence (IPV) after age 18. We used a weighted logistic regression to assess whether childhood violence exposure was associated with subsequent experience of IPV after age 18. Results: Adolescent girls and young women in Namibia had a statistically significant higher odds of experiencing IPV if they had experienced any childhood violence including physical, sexual, and/or emotional violence (adjusted odds ratio [aOR]: 2.93; 95% Confidence Interval [95% CI: 1.64-5.23). IPV was also significantly associated with childhood physical (aOR: 1.81; 95% CI: 1.07-3.05), sexual (aOR: 3.79; 95% CI: 2.54-5.67), or emotional (aOR: 2.39; 95% CI: 1.18-4.86) violence when each were considered separately. We also observed a dose-response relationship between the number of types of childhood violence and IPV experience as a young adult. Conclusions: Childhood violence is a significant predictor of subsequent violence revictimization by an intimate partner. This analysis provides unique insights on cycles of violence among adolescent girls and young women in Namibia and points to the need for interventions during childhood to prevent violence against children and break this cycle among young women in sub-Saharan Africa.

Multi-level Interventions to Promote Oral Pre-exposure Prophylaxis Use Among Adolescent Girls and Young Women: a Review of Recent Research.

PURPOSE OF REVIEW: This review summarizes interventions to promote HIV pre-exposure prophylaxis (PrEP) use among adolescent girls and young women (AGYW) in HIV endemic settings, while also highlighting gaps in our current measures of PrEP intervention success. RECENT FINDINGS: AGYW report challenges with PrEP use, although the field is currently grappling with defining metrics of optimal PrEP use applicable for AGYW with dynamic HIV prevention needs. Ongoing studies are exploring multilevel interventions to address barriers to PrEP use for AGYW. At the individual and interpersonal levels, mHealth, drug-level feedback, adherence counseling, peer groups, and PrEP decision-support interventions are acceptable and feasible for AGYW although limited effectiveness data are available. At the health facility and community levels, PrEP demand creation, modified PrEP refill schedules, and integrated PrEP and reproductive health services are also promising options to support PrEP use for AGYW. As PrEP delivery continues to expand, improved metrics of success and evidence on the effectiveness of multi-level adherence support interventions are needed to maximize the impact of PrEP for AGYW in HIV endemic settings. We present case studies of these intervention approaches but limited data are currently available on the effectiveness of these approaches. We will look toward forthcoming study results on the impact of PrEP interventions, including mHealth, drug-level feedback and other enhanced counseling, peer support, decision-support tools, PrEP demand creation, modified refills, and integrated service delivery, to determine the ideal package of PrEP support approaches for AGYW.

Assessing longitudinal patterns of depressive symptoms and the influence of symptom trajectories on HIV pre-exposure prophylaxis adherence among adolescent girls in the HPTN 082 randomized controlled trial.

INTRODUCTION: African adolescent girls and young women (AGYW) eligible for HIV pre-exposure prophylaxis (PrEP) experience high levels of depressive symptoms. Depression can reduce PrEP adherence among adults, although analyses have considered depression as a time-varying exposure rather than modelling distinct patterns of symptoms. The association between depressive symptoms and PrEP adherence has not been explored for AGYW. To address these gaps, we sought to understand depressive symptom trajectories among African AGYW initiating PrEP and the impact of time-varying depressive symptoms and symptom trajectories on PrEP adherence. METHODS: HPTN 082 was an open-label PrEP study among AGYW (ages 16 to 24) in Zimbabwe and South Africa from 2016 to 2018. Depressive symptoms were measured at enrolment and Weeks 13, 26 and 52, using the 10-item Center for Epidemiologic Studies scale; a score ≥10 is indicative of elevated depressive symptoms. PrEP adherence was defined as any detectable tenofovir diphosphate (TFV-DP) levels. Group-based trajectory modelling was used to model longitudinal patterns of depressive symptoms. We assessed psychosocial and behavioural predictors of depressive symptom trajectory membership (e.g. PrEP stigma, intimate partner violence [IPV], sexual behaviour). We modelled associations between (1) group trajectory membership and PrEP adherence at Week 52 and (2) time-varying depressive symptoms and PrEP adherence through follow-up. RESULTS: At enrolment, 179 (41.9%) participants had elevated depressive symptoms. Group-based trajectory models revealed persistent elevated depressive symptoms in 48.5%, declining symptoms in 9.4% and no consistent or mild depressive symptoms in 43.3%. AGYW who engaged in transactional sex, reported IPV, or had traumatic stress symptoms were more likely to be assigned to the persistent elevated symptom group compared with the consistent no/mild symptom group (Wald test p-value all <0.01). Participants assigned to the persistent elevated depressive symptom trajectory had a significantly lower risk of detectable TFV-DP at Week 52 than those in the no/mild symptom trajectory (adjusted prevalence ratio = 0.89; 95% CI: 0.80 to 0.98). Elevated depressive symptoms were significantly inversely associated with PrEP use throughout follow-up (adjusted relative risk = 0.73; 95% CI = 0.53 to 0.99). CONCLUSIONS: Persistent depressive symptoms were common among African AGYW seeking PrEP. Integration of depressive symptom screening and treatment into PrEP programmes may improve PrEP effectiveness among African women.

Intervening for HIV prevention and mental health: a review of global literature.

INTRODUCTION: Numerous effective HIV prevention options exist, including behaviour change interventions, condom promotion and biomedical interventions, like voluntary medical male circumcision and pre-exposure prophylaxis. However, populations at risk of HIV also face overlapping vulnerabilities to common mental disorders and severe mental illness. Mental health status can affect engagement in HIV risk behaviours and HIV prevention programmes. We conducted a narrative review of the literature on HIV prevention among key populations and other groups vulnerable to HIV infection to understand the relationship between mental health conditions and HIV prevention outcomes and summarize existing evidence on integrated approaches to HIV prevention and mental healthcare. METHODS: We searched five databases for studies published from January 2015 to August 2020, focused on HIV prevention and mental health conditions among key populations and individuals with serious mental illness. Studies were included if they evaluated an HIV prevention intervention or assessed correlates of HIV risk reduction and included assessment of mental health conditions or a mental health intervention. RESULTS AND DISCUSSION: We identified 50 studies meeting our inclusion criteria, of which 26 were randomized controlled trials or other experimental designs of an HIV prevention intervention with or without a mental health component. Behaviour change interventions were the most common HIV prevention approach. A majority of studies recruited men who have sex with men and adolescents. Two studies provided distinct approaches to integrated HIV prevention and mental health service delivery. Overall, a majority of included studies showed that symptoms of mental disorder or distress are associated with HIV prevention outcomes (e.g. increased risky sexual behaviour, poor engagement in HIV prevention behaviours). In addition, several studies conducted among groups at high risk of poor mental health found that integrating a mental health component into a behaviour change intervention or linking mental health services to combination prevention activities significantly reduced risk behaviour and mental distress and improved access to mental healthcare. CONCLUSIONS: Evidence suggests that mental health conditions are associated with poorer HIV prevention outcomes, and tailored integrated approaches are urgently needed to address overlapping vulnerabilities among key populations and other individuals at risk.

Use of fertility awareness methods as a component of safer conception for women in HIV-serodifferent relationships in Kenya.

BACKGROUND: For couples affected by HIV, and serodifferent couples in particular, pregnancy desire is often juxtaposed against the risk of HIV transmission between the couple and the potential neonate leading to thinking about measures to minimize risk of HIV transmission. We assess the use of fertility awareness methods [FAM] and evaluate the drivers of alignment between indicators of fertility and sexual behavior among HIV-serodifferent couples desiring pregnancy. METHODS: HIV-serodifferent couples from Thika, Kenya were enrolled into an open-label pilot evaluation of safer conception strategies. Women responded to daily 7-item short message service [SMS] surveys on FAM and sexual activity. Menstrual cycles were categorized as having condomless sex aligned, not aligned, or partially aligned to the predicted peak fertility. We used binomial logit models with generalized estimating equations to assess alignment between condomless sex during peak fertility days and FAM results. We used Cox proportional hazards to compare pregnancy incidence among months with sex and peak fertility aligned and mis-aligned. RESULTS: A total of 6929 SMS surveys across 252 menstrual cycles of 65 women were included. Reporting "sticky" cervical mucus (adjusted odds ratio [aOR]: 2.25, 95% confidence interval [95% CI]: 1.30, 3.90) and positive ovulation prediction kit [OPK] result (aOR: 2.07, 95% CI: 1.11, 3.86) were associated with increased likelihood of alignment of condomless sex during peak fertility. Pregnancy incidence was statistically similar among periods with sex aligned and not aligned with peak fertility. CONCLUSIONS: Among women engaged in a comprehensive safer conception program, a moderate percentage of women aligned condomless sex and predicted peak fertility days at least once. While FAM, particularly cervical mucus and OPK, are an inexpensive option for couples to consider using as a component of their safer conception strategies, antiretroviral-based strategies remain important to minimize risk.

Interventions to improve daily medication use among adolescents and young adults: what can we learn for youth pre-exposure prophylaxis services?

OBJECTIVE: Oral pre-exposure prophylaxis (PrEP) is an important HIV prevention method and studies have shown that young people ages 15-24 have difficulty adhering to daily PrEP. The field of PrEP delivery for young people is relatively nascent and lessons about potential PrEP adherence interventions could be learned from the larger evidence base of adherence interventions for other daily medications among youth. DESIGN: Systematic review of adherence support interventions for adolescents. METHODS: We searched PubMed, CINAHL, EMBASE, and PsycINFO through January 2020 for oral contraceptive pill (OCP), antiretroviral therapy (ART), asthma, and diabetes medication adherence interventions. We reviewed primary articles about OCP adherence interventions and reviewed systematic reviews for ART, asthma, and diabetes medication adherence interventions. Studies were retained if they included participants' ages 10-24 years; measured OCP, ART, asthma, or diabetes medication adherence; and were systematic reviews, randomized trials, or quasi-experimental studies. RESULTS: Fifteen OCP articles and 26 ART, diabetes, and asthma systematic reviews were included. Interventions that improved medication adherence for OCPs, ART, asthma, and diabetes treatment included reminder text messages, computer-based and phone-based support, and enhanced counseling. Multi-month prescriptions and same-day pill starts also were found to improve OCP adherence and continuation. Adolescent-friendly clinics and peer-based counseling significantly improved ART adherence, and telemedicine interventions improved diabetes medication adherence. CONCLUSION: Interventions that improve medication adherence among youth include enhanced counseling, extended pill supply, adolescent-friendly services, and text message reminders. PrEP programs could incorporate and evaluate such interventions for their impact on PrEP adherence and continuation among at-risk adolescents.

Narrative sexual histories and perceptions of HIV risk among young women taking PrEP in southern Africa: Findings from a novel participatory method.

Pre-exposure prophylaxis (PrEP) is an important HIV prevention method for adolescent girls and young women (AGYW) in Africa, who are at heightened risk of HIV infection. HIV risk perception is generally a powerful motivator for adoption of HIV prevention behaviours, including PrEP use. While HIV risk perceptions have been evaluated using quantitative measures, these seldom capture how individuals conceptualize and understand risk within local frameworks of meaning. More nuanced understanding may come from qualitative approaches that map these perceptions across the trajectory of sexual histories. Between 2016 and 2018, we implemented a novel participatory method to investigate risk perceptions in interviews with 32 participants in HPTN 082, a study of AGYW's use of PrEP in South Africa and Zimbabwe. Timelines were used to record narrative sexual histories and perceived HIV risk for each relationship. We found that women assessed HIV risk primarily based on their partners' personal qualities and behaviour (especially relating to infidelity); their subjective experience of being treated respectfully; and the practice of perceived 'risk reduction', including younger partners and condoms, even if used inconsistently. A narrative timeline approach grounded in an understanding of young women's sexual histories may increase critical reflection about HIV risks and facilitate risk-reduction counselling with this group.