Hearing Loss Detection and Early Intervention Strategies in Kenya.

Background: Thirty-four million children globally have disabling hearing loss, with the highest prevalence in low- and middle-income countries (LMICs). Early identification and management is crucial, yet barriers to screening and treatment of hearing loss are extensive in LMICs. Unaddressed hearing loss negatively impacts individuals and communities. The WHO's 2021 World Report on Hearing urges the development of Ear and Hearing Care (EHC) programs to improve access to all aspects of care, including screening, diagnostics, management, and developmental support. A joint Nairobi- and Seattle-based group convened in 2021 to discuss strategies for program development in Kenya, as presented in this paper. Findings: Developing a national EHC program must include the necessary support services for a child with a diagnosed hearing loss, while simultaneously promoting engagement of family, community, and healthcare workers. Existing government and healthcare system policies and priorities can be leveraged for EHC programming. Strategies for success include strengthening connections between policymakers at national, county, and municipal levels and local champions for the EHC agenda, with a concurrent focus on policy, early detection and intervention, habilitation, and family-centered care. Updates to health policy and funding to support the accessibility of services and equipment should focus on leveraging national healthcare coverage for hearing technologies and services, strengthening referral pathways, training to bolster the workforce, and metrics for monitoring and evaluation. Additional strategies to support forward progress include strategic engagement of partners and leveraging local partners for phased scale-up. Conclusions and Recommendations: Recommendations to strengthen EHC within the Kenyan health system include concurrent leverage of existing health policies and priorities, partner engagement, and strengthening referral pathways, monitoring and evaluation, and training. These strategies may be generalized to other countries too.

Estimating the costs of adolescent HIV care visits and an intervention to facilitate transition to adult care in Kenya.

INTRODUCTION: Adolescents with HIV in sub-Saharan Africa face challenges transitioning to adult HIV care, which can affect long-term HIV care adherence and retention. An adolescent transition package (ATP) focused on transition tools can improve post-transition clinical outcomes, but its implementation costs are unknown. METHODS: We estimated the average cost per patient of an HIV care visit and ATP provision to adolescents. Data was collected from 13 HIV clinics involved in a randomized clinical trial evaluating ATP in western Kenya. We conducted a micro-costing and activity-driven time estimation to assess costs from the provider perspective. We developed a flow-map, conducted staff interviews, and completed time and motion observation. ATP costs were estimated as the difference in average cost for an HIV care transition visit in the intervention compared to control facilities. We assessed uncertainty in costing estimates via Monte Carlo simulations. RESULTS: The average cost of an adolescent HIV care visit was 29.8USD (95%CI 27.5, 33.4) in the standard of care arm and 32.9USD (95%CI 30.5, 36.8) in the ATP intervention arm, yielding an incremental cost of 3.1USD (95%CI 3.0, 3.4) for the ATP intervention. The majority of the intervention cost (2.8USD) was due ATP booklet discussion with the adolescent. CONCLUSION: The ATP can be feasibly implemented in HIV care clinics at a modest increase in overall clinic visit cost. Our cost estimates can be used to inform economic evaluations or budgetary planning of adolescent HIV care interventions in Kenya.

Lower self-reported ART adherence among adolescents in boarding schools compared to day schools.

INTRODUCTION: Adolescents living with HIV (ALH) have poorer adherence to antiretroviral therapy (ART) than adults. Many ALH in sub-Saharan Africa (SSA) are enrolled in boarding schools where stigma is pervasive and may impact adherence. METHODS: We collected sociodemographic data, school information, medical history, and viral load (VL) data from ALH age 14-19 in 25 HIV clinics in 3 counties in Kenya. Using generalized estimating equations, we compared ART adherence in ALH attending day and boarding schools. RESULTS: Of 880 ALH, 798 (91%) were enrolled in school, of whom 189 (24%) were in boarding schools. Of those in school, median age was 16 (IQR: 15, 18), 55% were female, 78% had a parent as a primary caregiver, and 74% were on DTG-based ART. Median age at ART initiation was 6 years (IQR 3, 10).Overall, 227 (29%) ALH self-reported missing ART when school was in session (40% in boarding and 25% in day school). After adjusting for sociodemographic and HIV care characteristics, ALH in boarding schools were significantly more likely to self-report missing ART than those in day schools (adjusted Prevalence Ratio (aPR): 1.47, 95% CI 1.18, 1.83, p=0.001). Among 194 ALH, only 60% had undetectable (<20 copies/ml) HIV viral load (62% day schools and 51% boarding schools)(p=0.097). CONCLUSION: ALH had high self-reported non-adherence overall, with worse adherence among those in boarding schools. Schools remain a critical untapped resource for improving ALH outcomes.

Gaps and Opportunities for Strengthening In-School Support for Youth Living With HIV.

OBJECTIVES: With optimized antiretroviral treatment youth living with HIV (YLH) now spend most of their time in schools, making schools an important venue to optimize outcomes. We evaluated school support for YLH. METHODS: We conducted surveys with public secondary/high schools in 3 Kenyan counties (Nairobi, Homa Bay, and Kajiado) to determine policies and training related to HIV. Chi-squared tests and Poisson regression were used to compare policy availability and staff training by county HIV prevalence and school type. RESULTS: Of 512 schools in the 3 counties, we surveyed 100. The majority (60%) of schools surveyed had boarding facilities. The median student population was 406 (IQR: 200, 775). Only half (49%) of schools had medication use policies; more in boarding than day schools (65% vs 30%, p = .003). While most schools (82%) had clinic attendance policies; policy availability was higher in higher HIV prevalence counties (Homa Bay [100%], Nairobi [82%], Kajiado [56%], p < .05). Overall, 64% had confidentiality policies with higher policy availability in higher HIV prevalence regions (p < .05). Few schools had staff trained in HIV-related topics: HIV prevention (37%), HIV treatment (18%), HIV stigma reduction (36%). Few were trained in confidentiality (41%), psychosocial support (40%), or mental health (26%). Compared to day schools, boarding school were more likely to have staff trained in HIV prevention (prevalence ratio: 2.1 [95% confidence interval 1.0, 4.0], p = .037). CONCLUSION: In this survey of Kenyan schools, there were notable gaps in HIV care policy availability and training, despite high HIV burden. Development and implementation of national school HIV policies and staff training as well as strengthening clinic and family support may improve outcomes for YLH.

Effect of tuberculosis-HIV co-treatment on clinical and growth outcomes among hospitalized children newly initiating antiretroviral therapy.

OBJECTIVE: Evaluate effects of tuberculosis (TB)-HIV co-treatment on clinical and growth outcomes in children with HIV (CHIV). DESIGN: Longitudinal study among Kenyan hospitalized ART-naive CHIV in the PUSH trial (NCT02063880). METHODS: CHIV started ART within 2 weeks of enrollment; Anti-TB therapy was initiated based on clinical and TB diagnostics. Children were followed for 6 months with serial viral load, CD4%, and growth assessments [weight-for-age z -score (WAZ), height-for-age z -score (HAZ), and weight-for-height z -score (WHZ)]. TB-ART treated and ART-only groups were compared at 6 months post-ART for undetectable viral load (<40 c/ml), CD4% change, and growth using generalized linear models, linear regression, and linear mixed-effects models, respectively. RESULT: Among 152 CHIV, 40.8% (62) were TB-ART treated. Pre-ART, median age was 2.0 years and growth was significantly lower, and viral load significantly higher in the TB-ART versus ART-only group. After 6 months on ART, 37.2% of CHIV had undetectable viral load and median CD4% increased by 7.2% (IQR 2.0-11.6%) with no difference between groups. The TB-ART group had lower WAZ and HAZ over 6 month follow-up [WAZ -0.81 (95% CI: -1.23 to -0.38], P  < 0.001; HAZ -0.15 (95% CI: -0.29 to -0.01), P  = 0.030] and greater rate of WAZ increase in analyses unadjusted and adjusted for baseline WAZ [unadjusted 0.62 (95% CI: 0.18-1.07, P  = 0.006) or adjusted 0.58 (95% CI: 0.12-1.03, P  = 0.013)]. CONCLUSION: TB-HIV co-treatment did not adversely affect early viral suppression and CD4 + recovery post-ART. TB-ART-treated CHIV had more rapid growth reconstitution, but growth deficits persisted, suggesting need for continued growth monitoring.

Adolescent experiences, perceptions, and preferences for the process of HIV status disclosure in Kenya.

Introduction: Disclosure of HIV status to adolescents living with HIV has been associated with improved treatment outcomes. However, there are limited data regarding the experiences of, perceptions of, and preferences for the process of disclosure of HIV status among adolescents and young adults living with HIV (AYLH), especially in sub-Saharan Africa. Methods: Young adults living with HIV from 20 HIV clinics in Kenya who participated in a clinical trial evaluating the effectiveness of a disclosure and transition package completed an anonymous survey in 2019. We described their experiences and preferences using counts and proportions and assessed factors associated with satisfaction with the disclosure process using linear regression, reporting age-adjusted mean differences (aMD), and 95% confidence intervals (95%CIs). Results: Of the 375 enrolled AYLH, 265 (71%) had perinatally acquired HIV, of whom 162 (61%) were female. The median age of the enrolled AYLH was 16 years (IQR: 14-19 years), and all of them were on antiretroviral therapy (ART). For over half (55%) of the participants, caregivers disclosed their HIV status, and 57% preferred that their caregivers disclose the status to them. Most (78%) of the participants preferred full disclosure by 12 years of age. The majority (69%) believed the disclosure was planned, and 11% suspected being HIV positive before the disclosure. Overall, 198 (75%) AYLH reported that they were ready for disclosure when it happened, and 86% were satisfied with the process. During both pre-disclosure (67 and 70%, respectively) and post-disclosure (>75% for each), AYLH felt supported by the clinic and caregivers. Factors associated with higher satisfaction with the disclosure process were pre-disclosure clinic support (aMD: 0.19 [95%CI: 0.05-0.33]) and pre-disclosure (aMD: 0.19 [0.06-0.31]) and post-disclosure (aMD: 0.17 [0.03-0.31]) caregiver support. AYLH who suspected they were HIV positive before they were disclosed to tended to have lower satisfaction when compared to those who never suspected (aMD: -0.37 [-0.74-(-0.01)]). Overall, they reported that disclosure positively influenced their ART adherence (78%), clinic attendance (45%), and communication with caregivers (20%), and 40% reported being happier after disclosure. Conclusion: Young adults living with HIV advocated for an appropriately timed disclosure process with the involvement of caregivers and healthcare workers (HCWs). Support from caregivers and HCWs before and during disclosure is key to improving their disclosure experience.

Neurodevelopment of children who are HIV-exposed and uninfected in Kenya.

INTRODUCTION: Predictors of neurodevelopment among children who are HIV-exposed uninfected (CHEU) are poorly understood. METHODS: Mothers with and without HIV and their children were enrolled during 6-week postnatal care visits across seven sites in Kenya between March 2021 and June 2022. Infant neurodevelopment was assessed using the Malawi Developmental Assessment Tool, including social, language, fine motor and gross motor domains. We used multivariate linear mixed effects models to identify associations between 1-year neurodevelopment scores, HIV and antiretroviral therapy (ART) exposures, and household factors, adjusted for potential confounders and clustered by the site. RESULTS: At 1-year evaluation, CHEU (n = 709) and children who are HIV-unexposed uninfected (CHUU) (n = 715) had comparable median age (52 weeks) and sex distribution (49% vs. 52% female). Mothers living with HIV were older (31 vs. 27 years), had lower education (50% vs. 26% primary) and were more likely to be report moderate-to-severe food insecurity (26% vs. 9%) (p < 0.01 for all). Compared to CHUU, CHEU had higher language scores (adjusted coeff: 0.23, 95% CI: 0.06, 0.39) and comparable social, fine and gross motor scores. Among all children, preterm birth was associated with lower gross motor scores (adjusted coeff: -1.38, 95% CI: -2.05, -0.71), food insecurity was associated with lower social scores (adjusted coeff: -0.37, 95% CI: -0.73, -0.01) and maternal report of intimate partner violence (IPV) was associated with lower fine motor (adjusted coeff: -0.76, 95% CI: -1.40, -0.13) and gross motor scores (adjusted coeff: -1.07, 95% CI: -1.81, -0.33). Among CHEU, in utero efavirenz (EFV) exposure during pregnancy was associated with lower gross motor scores compared to dolutegravir (DTG) exposure (adjusted coeff: -0.51, 95% CI: -1.01, -0.03). Lower fine and gross motor scores were also associated with having a single or widowed mother (adjusted coeff: -0.45, 95% CI: -0.87, -0.03) or a deceased or absent father (adjusted coeff: -0.81, 95% CI: -1.58, -0.05), respectively. CONCLUSIONS: Biologic and social factors were associated with child neurodevelopment. Despite socio-demographic differences between CHEU and CHUU, 1-year neurodevelopment was similar. Addressing IPV and food insecurity may provide benefits regardless of maternal HIV status. DTG use was associated with higher neurodevelopmental scores in CHEU, compared to EFV regimens, potentially contributing to a lack of neurodevelopmental difference between CHEU and CHUU.

Neurodevelopment among children exposed to HIV and uninfected in sub-Saharan Africa.

INTRODUCTION: The population of 16 million children exposed to HIV and uninfected (CHEU) under 15 years of age continues to expand rapidly, and the estimated prevalence of CHEU exceeds 20% in several countries in sub-Saharan Africa with high HIV prevalence. Some evidence suggests that CHEU experience suboptimal neurodevelopmental outcomes compared to children born to women without HIV. In this commentary, we discuss the latest research on biologic and socio-behavioural factors associated with neurodevelopmental outcomes among CHEU. DISCUSSION: Some but not all studies have noted that CHEU are at risk of poorer neurodevelopment across multiple cognitive domains, most notably in language and motor skills, in diverse settings, ages and using varied assessment tools. Foetal HIV exposure can adversely influence infant immune function, structural brain integrity and growth trajectories. Foetal exposure to antiretrovirals may also influence outcomes. Moreover, general, non-CHEU-specific risk factors for poor neurodevelopment, such as preterm birth, food insecurity, growth faltering and household violence, are amplified among CHEU; addressing these factors will require multi-factorial solutions. There is a need for rigorous harmonised approaches to identify children at the highest risk of delay. In high-burden HIV settings, existing maternal child health programmes serving the general population could adopt structured early child development programmes that educate healthcare workers on CHEU-specific risk factors and train them to conduct rapid neurodevelopmental screening tests. Community-based interventions targeting parent knowledge of optimal caregiving practices have shown to be successful in improving neurodevelopmental outcomes in children and should be adapted for CHEU. CONCLUSIONS: CHEU in sub-Saharan Africa have biologic and socio-behavioural factors that may influence their neurodevelopment, brain maturation, immune system and overall health and wellbeing. Multidisciplinary research is needed to disentangle complex interactions between contributing factors. Common environmental and social risk factors for suboptimal neurodevelopment in the general population are disproportionately magnified within the CHEU population, and it is, therefore, important to draw on existing knowledge when considering the socio-behavioural pathways through which HIV exposure could impact CHEU neurodevelopment. Approaches to identify children at greatest risk for poor outcomes and multisectoral interventions are needed to ensure optimal outcomes for CHEU in sub-Saharan Africa.

Identifying HIV-exposed uninfected children and adolescents in resource-limited settings: the HOPE study experience.

HIV-exposed uninfected (HEU) children and adolescents are at higher risk of poor outcomes compared to HIV-unexposed children (HUU). In program settings, it is critical to understand how to identify HEU for screening services. We describe our experience identifying HEU for a neurodevelopment and mental health screening study. We recruited mothers living with HIV (MLHIV) and mothers not living with HIV (MNHIV) and enrolled their HEU or HUU children. We summarise the reasons for ineligibility and recruitment challenges. Among MLHIV, their child's ineligibility increased with age: 12%, 27%, 50% and 80% in age groups 3-6, 7-10, 11-14, and 15-18, respectively (p < 0.001). Reasons for ineligibility were unknown maternal HIV status during pregnancy or breastfeeding (30%), and maternal disinterest due to fear of inadvertent disclosure of their HIV status to older youth. Recruiting older HEU youth is challenging. Maternal concerns of self-disclosing their HIV status impedes identification of older HEU.

Characterizing provider-led adaptations to mobile phone delivery of the Adolescent Transition Package (ATP) in Kenya using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS): a mixed methods approach.

BACKGROUND: The COVID-19 pandemic resulted in disruptions to routine HIV services for youth living with HIV (YLH), provoking rapid adaptation to mitigate interruptions in care. The Adolescent Transition to Adult Care for HIV-infected adolescents (ATTACH) study (NCT03574129) was a hybrid I cluster randomized trial testing the effectiveness of a healthcare worker (HCW)-delivered disclosure and transition intervention - the Adolescent Transition Package (ATP). During the pandemic, HCWs leveraged phone delivery of the ATP and were supported to make adaptations. We characterized real-time, provider-driven adaptations made to support phone delivery of the ATP. METHODS: We conducted continuous quality improvement (CQI) meetings with HCWs involved in phone delivery of the ATP at 10 intervention sites. CQI meetings used plan-do-study-act (PDSA) cycles and were audio-recorded. Adaptations were coded by two-independent coders using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS). Adaptation testing outcomes (adopt, retest, or abandon) and provider experience implementing the adaptations were also recorded. We summarized adaptation characteristics, provider experience, and outcomes. RESULTS: We identified 72 adaptations, 32 were unique. Overall, adaptations included modification to context (53%, n = 38), content (49%, n = 35), and evaluation processes (13%, n = 9). Context adaptations primarily featured changes to personnel, format, and setting, while content and evaluation adaptations were frequently achieved by simple additions, repetition, and tailoring/refining of the phone delivery strategy. Nine adaptations involved abandoning, then returning to phone delivery. HCWs sought to increase reach, improve fidelity, and intervention fit within their context. Most adaptations (96%, n = 69) were perceived to increase the feasibility of phone delivery when compared to before the changes were introduced, and HCWs felt 83% (n = 60) of adaptations made phone delivery easier. Most adaptations were either incorporated into routine workflows (47%) or tested again (47%). CONCLUSION: Adaptation of phone delivery was a feasible and effective way of addressing challenges with continuity of care for YLH during the COVID-19 pandemic. Adaptations were primarily context adaptions. While FRAME-IS was apt for characterizing adaptations, more use cases are needed to explore the range of its utility. TRIAL REGISTRATION: Trial registered on ClinicalTrial.gov as NCT03574129.

"We can tell a good teacher who cares, understands, and can be confidential about it": youth and caregiver experiences with HIV disclosure to schools in Kenya.

Introduction: Disclosure of one's HIV status to others is often difficult due to the fear of stigma. However, disclosure may facilitate receiving social support. Many youth living with HIV (YLH) are enrolled in school as better treatments have improved the health and survival of children with HIV. There is no structured process for disclosure at school for YLH and their caregivers. We sought to understand school disclosure experiences among YLH and their caregivers and assess the need for the development of a structured disclosure intervention tailored to school settings. Methods: We conducted in-depth qualitative interviews with 28 school-going YLH aged 14-19 years and 24 caregivers of YLH. Interviews were conducted in English and Swahili, transcribed, and translated. The transcripts were uploaded to Atlas.ti 9 for thematic analysis. Results: YLH and caregivers clearly articulated the benefits of disclosing to school staff. Disclosure to school staff was seen as the first step to receiving support for medication storage, adherence, and clinic attendance. However, disclosure was also perceived to be a very complicated and stressful process. Fear of stigma drove caregivers and YLH toward careful planning of when and to whom to disclose. Distrust of school staff was a significant barrier to disclosure, even among those who clearly articulated the benefits of disclosure. Disclosure to school staff largely resulted in positive experiences; the immediate reactions were positive or somewhat neutral and confidentiality was upheld. The anticipated benefits of practical and emotional support were demonstrated by the school staff to whom the HIV information was disclosed. Conclusion: Disclosure of HIV status to someone at school is necessary to receive support for medication adherence. Stigma and the lack of structured support for the disclosure process at school often hinder YLH and their caregivers from disclosing. YLH would benefit from better support at schools, including policies to facilitate disclosure that address the caregiver and YLH's fear of stigma and loss of confidentiality. School policies could also provide guidance on whom to disclose to and available post-disclosure support.

Mortality and Loss to Follow-Up Among Adolescents and Young Adults Attending HIV Care Programs in Kenya.

Mortality and loss to follow-up (LTFU) among adolescents and youth living with HIV (AYLHIV) remain high. We evaluated mortality and LTFU during the test and treat era. We abstracted medical records of AYLHIV for 10-24 years between January 2016 and December 2017 in 87 HIV clinics in Kenya. Using competing risk survival analysis, we compared incidence rates and determined correlates of mortality and LTFU among newly enrolled [<2 years since antiretroviral therapy (ART) initiation] and AYLHIV on ART for ≥2 years. Among 4201 AYLHIV, 1452 (35%) and 2749 (65%) were new enrollments and on ART for ≥2 years, respectively. AYLHIV on antiretroviral therapy (ART) for ≥2 years were younger and more likely to have perinatally acquired HIV (p < 0.001). Incidence of mortality and LTFU per 100 person-years were 2.32 [95% confidence interval (CI): 1.64-3.28] and 37.8 (95% CI: 34.7-41.3), respectively, among new enrollments and 1.22 (95% CI: 0.94-1.59) and 10.2 (95% CI: 9.3-11.1), respectively, among those on ART for ≥2 years. New enrollments had almost twice higher risk of mortality [subdistribution hazard ratio (sHR) 1.92 (1.30, 2.84), p = 0.001] and sevenfold higher risk of LTFU [sHR 7.71 (6.76, 8.79), p < 0.001] than those on ART for ≥2 years. Among new enrollments, mortality was higher in males and those with World Health Organization (WHO) stage III/IV disease at enrollment, and LTFU was associated with pregnancy, older age, and nonperinatal acquisition. Female sex and WHO stage (I/II) were associated with LTFU among those on ART for ≥2 years. During the study period from January 1, 2016, to December 31, 2017, the mortality incidence observed did not demonstrate improvement from earlier studies despite universal test and treat and better ART regimens. This trial was registered with ClinicalTrials.gov, NCT03574129.

'They should show them love even if their status of being HIV positive is known': Youth and caregiver stigma experience and strategies to end HIV stigma in schools.

OBJECTIVE: HIV stigma and discrimination is widespread in sub-Saharan Africa and is associated with poor clinical outcomes. Schools play a critical role in the life of youth and have been identified as a potentially stigmatising environment. We sought to explore school HIV stigma drivers, facilitators, manifestations and outcomes among youth living with HIV (YLH) as well as potential stigma reduction interventions in Kenya. METHODS: Semi-structured in-depth qualitative interviews with 28 school-attending YLH aged 14-19 years and 24 caregivers of YLH were analysed using directed content analysis. Results were summarised using the Health and Stigma Framework. RESULTS: Drivers and facilitators of HIV stigma in the school environment included misconceptions about HIV transmission, HIV treatment outcomes and long-term overall health of people living with HIV. HIV stigma manifested largely as gossip, isolation and loss of friendships. Fear of HIV stigma or experienced stigma resulted in poor adherence to antiretroviral treatment-particularly among YLH in boarding schools-and poor mental health. Stigma also impacted school choice (boarding vs. day school) and prevented HIV disclosure to schools which was necessary for optimal support for care. Proposed interventions to address HIV stigma in schools included HIV education, psychosocial support for YLH, support for HIV disclosure to schools while ensuring confidentiality and building YLH resilience. CONCLUSION: There is an urgent need to develop interventions to address HIV stigma in schools to ensure optimised health and social outcomes for YLH. Future studies to understand the most effective and efficient interventions are needed.

Demand creation for HIV testing services: A systematic review and meta-analysis.

BACKGROUND: HIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally. METHODS AND FINDINGS: The following electronic databases were searched through September 28, 2021: PubMed, PsycInfo, Cochrane CENTRAL, CINAHL Complete, Web of Science Core Collection, EMBASE, and Global Health Database; we searched IAS and AIDS conferences. We systematically searched for randomized controlled trials (RCTs) that compared any demand creation intervention (incentives, mobilization, counseling, tailoring, and digital interventions) to either a control or other demand creation intervention and reported HTS uptake. We pooled trials to evaluate categories of demand creation interventions using random-effects models for meta-analysis and assessed study quality with Cochrane's risk of bias 1 tool. This study was funded by the WHO and registered in Prospero with ID CRD42022296947. We screened 10,583 records and 507 conference abstracts, reviewed 952 full texts, and included 124 RCTs for data extraction. The majority of studies were from the African (N = 53) and Americas (N = 54) regions. We found that mobilization (relative risk [RR]: 2.01, 95% confidence interval [CI]: [1.30, 3.09], p < 0.05; risk difference [RD]: 0.29, 95% CI [0.16, 0.43], p < 0.05, N = 4 RCTs), couple-oriented counseling (RR: 1.98, 95% CI [1.02, 3.86], p < 0.05; RD: 0.12, 95% CI [0.03, 0.21], p < 0.05, N = 4 RCTs), peer-led interventions (RR: 1.57, 95% CI [1.15, 2.15], p < 0.05; RD: 0.18, 95% CI [0.06, 0.31], p < 0.05, N = 10 RCTs), motivation-oriented counseling (RR: 1.53, 95% CI [1.07, 2.20], p < 0.05; RD: 0.17, 95% CI [0.00, 0.34], p < 0.05, N = 4 RCTs), short message service (SMS) (RR: 1.53, 95% CI [1.09, 2.16], p < 0.05; RD: 0.11, 95% CI [0.03, 0.19], p < 0.05, N = 5 RCTs), and conditional fixed value incentives (RR: 1.52, 95% CI [1.21, 1.91], p < 0.05; RD: 0.15, 95% CI [0.07, 0.22], p < 0.05, N = 11 RCTs) all significantly and importantly (≥50% relative increase) increased HTS uptake and had medium risk of bias. Lottery-based incentives and audio-based interventions less importantly (25% to 49% increase) but not significantly increased HTS uptake (medium risk of bias). Personal invitation letters and personalized message content significantly but not importantly (<25% increase) increased HTS uptake (medium risk of bias). Reduced duration counseling had comparable performance to standard duration counseling (low risk of bias) and video-based interventions were comparable or better than in-person counseling (medium risk of bias). Heterogeneity of effect among pooled studies was high. This study was limited in that we restricted to randomized trials, which may be systematically less readily available for key populations; additionally, we compare only pooled estimates for interventions with multiple studies rather than single study estimates, and there was evidence of publication bias for several interventions. CONCLUSIONS: Mobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.

Addressing the Know-Do Gap in Adolescent HIV: Framing and Measuring Implementation Determinants, Outcomes, and Strategies in the AHISA Network.

Implementation science (IS) uses systematic methods to close gaps between research and practice by identifying and addressing barriers to implementation of evidence-based interventions (EBIs). To reach UNAIDS HIV targets, IS can support programs to reach vulnerable populations and achieve sustainability. We studied the application of IS methods in 36 study protocols that were part of the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA). Protocols focused on youth, caregivers, or healthcare workers in high HIV-burden African countries and evaluated medication, clinical and behavioral/social EBIs. All studies measured clinical outcomes and implementation science outcomes; most focused on early implementation outcomes of acceptability (81%), reach (47%), and feasibility (44%). Only 53% used an implementation science framework/theory. Most studies (72%) evaluated implementation strategies. Some developed and tested strategies, while others adapted an EBI/strategy. Harmonizing IS approaches allows cross study learning and optimization of delivery of EBIs and could support attainment of HIV goals.

"When they are all grown, I will tell them": Experience and perceptions of parental self-disclosure of HIV status to children in Nairobi, Kenya.

BACKGROUND: There is mixed evidence on the influence of self-disclosure of one's HIV status on mental health, health behaviours and clinical outcomes. We studied the patterns of self-disclosure among parents living with HIV, and factors that influence parental disclosure. METHODS: This mixed-methods study was among adults in HIV care participating in a study assessing the uptake of pediatric index-case testing. They completed a survey to provide demographic and HIV-related health information, and assess self-disclosure to partners, children and others. We ran generalized linear models to determine factors associated with disclosure and reported prevalence ratios (PR). Eighteen participants also participated in in-depth interviews to explore perceived barriers and facilitators of self-disclosure to one's child. A content analysis approach was used to analyze interview transcripts. RESULTS: Of 493 caregivers, 238 (48%) had a child ≥ 6 years old who could potentially be disclosed to about their parent's HIV status. Of 238 participants, 205 (86%) were female, median age was 35 years, and 132 (55%) were in a stable relationship. Among those in a stable relationship, 96 (73%) knew their partner's HIV status, with 79 (60%) reporting that their partner was living with HIV. Caregivers had known their HIV status for a median 2 years, and the median age of their oldest child was 11 years old. Older caregiver age and older first born child's age were each associated with 10% higher likelihood of having disclosed to a child (PR: 1.10 [1.06-1.13] and PR: 1.10 [1.06-1.15], per year of age, respectively). The child's age or perceived maturity and fear of causing anxiety to the child inhibited disclosure. Child's sexual activity was a motivator for disclosure, as well as the belief that disclosing was the "right thing to do". Caregivers advocated for peer and counseling support to gain insight on appropriate ways to disclose their status. CONCLUSIONS: Child's age is a key consideration for parents to disclose their own HIV status to their children. While parents were open to disclosing their HIV status to their children, there is a need to address barriers including anticipated stigma, and fear that disclosure will cause distress to their children.

Predictors of intact HIV DNA levels among children in Kenya.

OBJECTIVE: We determined predictors of both intact (estimate of replication-competent) and total (intact and defective) HIV DNA in the reservoir among children with HIV. DESIGN: HIV DNA in the reservoir was quantified longitudinally in children who initiated antiretroviral therapy (ART) at less than 1 year of age using a novel cross-subtype intact proviral DNA assay that measures both intact and total proviruses. Quantitative PCR was used to measure pre-ART cytomegalovirus (CMV) viral load. Linear mixed effects models were used to determine predictors of intact and total HIV DNA levels (log 10 copies/million). RESULTS: Among 65 children, median age at ART initiation was 5 months and median follow-up was 5.2 years; 86% of children had CMV viremia pre-ART. Lower pre-ART CD4 + percentage [adjusted relative risk (aRR): 0.87, 95% confidence intervals (95% CI): 0.79-0.97; P  = 0.009] and higher HIV RNA (aRR: 1.21, 95% CI: 1.06-1.39; P  = 0.004) predicted higher levels of total HIV DNA during ART. Pre-ART CD4 + percentage (aRR: 0.76, 95% CI: 0.65-0.89; P < 0.001), CMV viral load (aRR: 1.16, 95% CI: 1.01-1.34; P  = 0.041), and first-line protease inhibitor-based regimens compared with nonnucleoside reverse transcriptase-based regimens (aRR: 1.36, 95% CI: 1.04-1.77; P  = 0.025) predicted higher levels of intact HIV DNA. CONCLUSION: Pre-ART immunosuppression, first-line ART regimen, and CMV viral load may influence establishment and sustainment of intact HIV DNA in the reservoir.

Tuberculosis Preventative Therapy Initiation and Completion Among Adolescents and Young Adults Living With HIV in Kenya.

BACKGROUND: Tuberculosis is the leading cause of death among adolescents and young adults living with HIV (YWHIV) and their heightened risk warrants deeper understanding of utilization of tuberculosis-prevention measures within HIV care. SETTING: Retrospective study using clinic surveys and medical record data from 86 Kenyan HIV clinics. METHODS: Clinic surveys obtained information on tuberculosis preventive therapy (TPT) services. Medical records of YWHIV were abstracted. Bivariate and multivariate analyses used generalized linear models to determine individual-level and clinic-level cofactors of TPT initiation and completion. RESULTS: Among 10,328 eligible YWHIV, 4337 (42.0%) initiated TPT. Of 3295 with ≥6 months follow-up, 1774 (53.8%) completed TPT. A lower patient-to-staff ratio was a clinic-level cofactor of TPT initiation ( P = 0.044) and completion ( P = 0.004); designated adolescent areas were associated with TPT initiation {prevalence ratio 2.05 [95% confidence interval (CI): 1.46 to -2.88]}. Individual cofactors of TPT initiation included younger age at HIV-care enrollment [relative risk (RR) 0.85 (95% CI: 0.80 to 0.90)] and antiretroviral therapy (ART) duration [1-2 vs. <1 year RR 1.31 (95% CI: 1.18 to 1.45)]. TPT completion was associated with younger age [RR 0.91 (95% CI: 0.85 to 0.98)] and ART duration [2-5 vs. <1 year RR 1.27 (95% CI: 1.03 to 1.57)]. In multivariate models, TPT initiation was associated with younger age and ART duration [1-2 vs. 1 year; adjusted RR 1.30 (95% CI: 1.16 to 1.46)] and TPT completion with ART duration [2-5 vs. 1 year adjusted RR 1.23 (95% CI: 0.99 to 1.52)]. CONCLUSION: Over half of YWHIV did not initiate and >40% did not complete TPT, with distinct clinic-level and individual-level cofactors. Approaches to enhance adolescent-friendly infrastructure and support older YWHIV are necessary to improve TPT use.