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.

Pediatric HIV Pre-test Informational Video is Associated with Higher Knowledge Scores Compared to Counselor-Delivered Information.

Video-based pre-test information is used in high resource settings to increase HIV testing coverage but remains untested in resource-limited settings. We conducted formative and evaluative focus group discussions with healthcare workers (HCWs) and caregivers of children in Kenya to develop and refine a pediatric HIV pre-test informational video. We then assessed HIV knowledge among caregivers sequentially enrolled in one of three pre-test information groups: (1) individual HCW-led (N = 50), (2) individual video-based (N = 50), and (3) group video-based (N = 50) sessions. A brief video incorporating information on national pediatric testing, modes of HIV transmission, and dramatized testimonials of caregivers who tested children was produced in three languages. Compared to individual HCW-led sessions (mean: 7.2/9; standard deviation [SD]: 1.3), both the group video-based (mean: 7.7; SD: 0.9) and individual video-based (mean: 7.6; SD: 0.9) sessions had higher mean knowledge scores. Video-based pre-test information could enhance existing pediatric HIV testing services.

The Psychosocial Effects of the COVID-19 Pandemic on Youth Living with HIV in Western Kenya.

The objective of this study was to assess psychosocial effects of COVID-19 among adolescents living with HIV (ALHIV) in Kenya and to assess the feasibility of conducting behavioral surveys by phone. We adapted our protocol to administer telephone rather than in-person follow-up surveys and included questions about COVID-19. The majority of participants (99%) reported having heard of COVID-19; 23% reported no longer being able to go outside, 17% reported that they could no longer go to their regular clinic for medical care, and 3% reported that they could no longer get medication refills. PHQ-9 screening identified 9% (n = 45) with mild depression symptoms, and 1% (n = 3) with moderate-to-severe depression symptoms. Young adults 20-24 years old had more mild to severe depressive symptoms than the younger age groups (p < 0.001). Offering remote peer-support or mental health care, continuing to offer differentiated care services, and considering financial support will support the health and well-being of ALHIV.

Financial Incentives for Pediatric HIV Testing (FIT): Caregiver Insights on Incentive Mechanisms, Focus Populations, and Acceptability for Programmatic Scale Up.

Children living with HIV experience gaps in HIV testing globally; scaling up evidence-based testing strategies is critical for preventing HIV-related mortality. Financial incentives (FI) were recently demonstrated to increase uptake of pediatric HIV testing. As part of this qualitative follow-up study to the FIT trial (NCT03049917) conducted in Kenya, 54 caregivers participated in individual interviews. Interview transcripts were analyzed to identify considerations for scaling up FI for pediatric testing. Caregivers reported that FI function by directly offsetting costs or nudging caregivers to take action sooner. Caregivers found FI to be feasible and acceptable for broader programmatic implementation, and supported use for a variety of populations. Some concerns were raised about unintended consequences of FI, including caregivers bringing ineligible children to collect incentives and fears about the impact on linkage to care and retention if caregivers become dependent on FI.

What happens at adolescent and young adult HIV clinics? A national survey of models of care, transition and disclosure practices in Kenya.

OBJECTIVE: Tailored services for adolescents and young adults (AYA) living with HIV may improve treatment outcomes. We surveyed HIV clinics throughout Kenya to determine AYA clinic practices, disclosure and transition services. METHODS: We deployed a mobile team to conduct surveys in a random sample of 102 public HIV clinics with> 300 total clients. Data were collected from healthcare workers offering AYA services who had >6 months of experience delivering AYA care. RESULTS: Of 102 surveyed HIV clinics, almost all (101/102) had the same staff to provide services to all age groups. AYA-specific services included dedicated clinic days (91%), the majority being on weekends (57%) and designated clinic spaces (20%). Activities to support AYA retention and adherence were common (support groups [97%] and HIV literacy meetings [93%]). Fewer clinics offered more holistic care, including psychosocial support (16%) and career education (2%), posted additional staff during the AYA day (17%), provided food (17%) or had sporting activities (10%) as incentives. Tracking of disclosure of HIV status to AYA was common (87%). In 40% of clinics, disclosure discussions with caregivers or AYA occurred a median of 2 years later in practice than stated in clinic policy. Transition was not routinely tracked, and definitions were heterogeneous. Median age at transition was reported as 20 years (range: 14-30 years). CONCLUSION: HIV programmes have implemented varied approaches to enhance AYA services that could be leveraged to support transition to adult services. Research on the impact of these services on health outcomes is needed.

OBJECTIF: Des services taillés sur mesure pour les adolescents et les jeunes adultes (AJA) vivant avec le VIH peuvent améliorer les résultats du traitement. Nous avons mené une surveillance des cliniques VIH à travers le Kenya pour déterminer les pratiques, la divulgation et les services de transition dans les cliniques AJA. MÉTHODES: Nous avons déployé une équipe mobile pour mener des enquêtes sur un échantillon aléatoire de 102 cliniques publiques du VIH avec >300 patients au total. Les données ont été recueillies auprès d'agents de santé offrant des services AJA qui avaient >6 mois d'expérience dans la prestation de soins AJA. RÉSULTATS: Sur 102 cliniques VIH surveillées, presque toutes (101/102) avaient les mêmes personnels pour fournir des services à tous les groupes d'âge. Les services spécifiques AJA comprenaient des journées de clinique dédiées (91%), la majorité étant le week-end (57%) et des espaces de clinique désignés (20%). Les activités visant à soutenir la rétention et l'adhésion à l'AJA étaient courantes (groupes de soutien [97%] et réunions d'éducation sur le VIH [93%]). Peu de cliniques offraient de soins plus holistiques, y compris un soutien psychosocial (16%) et une formation professionnelle (2%), détachaient du personnel supplémentaire pendant la journée AJA (17%), fournissait de la nourriture (17%) ou pratiquaient des activités sportives (10%) comme des incitations. Le suivi de la divulgation du statut VIH aux AJA était courant (87%). Dans 40% des cliniques, les discussions de divulgation avec les soignants ou AJA ont eu lieu en moyenne 2 ans plus tard dans la pratique que ce qui est indiqué dans la politique de la clinique. La transition n'était pas systématiquement suivie et les définitions étaient hétérogènes. L'âge médian au moment de la transition était de 20 ans (intervalle: 14-30 ans). CONCLUSION: Les programmes de lutte contre le VIH ont mis en œuvre diverses approches pour améliorer les services AJA qui pourraient être exploitées pour soutenir la transition vers les services pour adultes. Des recherches sur l'impact de ces services sur les résultats de santé sont nécessaires.

Newly diagnosed HIV positive children: a unique index case to improve HIV diagnosis and linkage to care of parents.

Newly diagnosed HIV positive children may be unique index cases to identify undiagnosed parents. Data was used from the Pediatric Urgent Start of HAART (NCT02063880) trial, which enrolled hospitalized, ART-naïve, HIV positive children ages 0-12 years in Kenya. Exact McNemar's tests were used to compare proportions of mothers and fathers tested for HIV, linked to care, and on ART at baseline and 6 months. This analysis included 87 newly diagnosed children with HIV who completed 6 months of follow-up. Among 83 children with living mothers, there were improvements in maternal linkage to care and treatment comparing baseline to 6 months (36% vs. 78%; p < 0.0001 and 22% vs. 52%; p < 0.0001). Among 80 children with living fathers, there were increases from baseline to 6 months in the number of fathers who knew the child's HIV status (34% vs. 78%; p < 0.0001), fathers ever tested for HIV (43% vs. 65%; p < 0.0001), fathers ever tested HIV positive (21% vs. 43%; p < 0.0001), fathers ever linked to care (15% vs. 35%; p < 0.0001), and fathers ever initiated on ART (11% vs. 23%; p = 0.0039). Newly diagnosed HIV positive children can be important index cases to identify parents with undiagnosed HIV or poor engagement in care.

Managing the transition from paediatric to adult care for HIV, Kenya.

Expansion of access to diagnosis and treatment for human immunodeficiency virus (HIV) and a high incidence of HIV infection in adolescence has resulted in a growing population of adolescents and young adults living with HIV. The prevalence of poor retention in care, insufficient viral suppression and loss to follow-up are higher among adolescents and young adults compared with other age groups. Poor outcomes could be attributed to psychosocial changes during adolescence, but also to poor transitional care from paediatric to adult HIV services. In many countries, transition processes remain poorly defined and unstructured, which may jeopardize treatment adherence and retention. We describe existing definitions of transition and transition frameworks, and key elements of transition as proposed by key national stakeholders in Kenya. Our consensus definition of transition is "a planned process by which adolescents and young adults living with HIV, and their caregivers, are empowered with knowledge and skills to enable them to independently manage their health." Transition should begin soon after disclosure of HIV status until an adolescent gains the necessary knowledge and skills and is willing to move to adult services, or by 25 years of age. Proposed key elements of transition are: target ages for milestone achievement; readiness assessment; caregiver involvement and communication with adult clinics; flexibility to return to adolescent or paediatric clinics; group transition; and considerations for adolescents with special needs. Retention in care, linkage to care and viral suppression are important markers of transition success. Proposed definitions and key elements could provide a framework for structuring transition programmes in other countries.

L'accès élargi au diagnostic et au traitement du virus de l'immunodéficience humaine (VIH) et l'incidence élevée de l'infection par le VIH à l'adolescence ont entraîné une hausse de la population d'adolescents et de jeunes adultes atteints du VIH. La prévalence de mauvais continuums de soins, de suppressions virales insuffisantes et d'interruptions du suivi est plus élevée chez les adolescents et les jeunes adultes que dans d'autres groupes d'âge. Ces mauvais résultats peuvent être attribués aux changements psychosociaux qui interviennent à l'adolescence, mais aussi à la médiocrité de la transition entre les services de soins pédiatriques et adultes du VIH. En Afrique subsaharienne, les processus de transition sont mal définis et peu structurés, ce qui peut nuire au respect et à la poursuite des traitements. Nous décrivons ici les définitions existantes de la transition et des cadres de transition, ainsi que les éléments clés de la transition proposés par les principales parties prenantes nationales du Kenya. Notre définition consensuelle de la transition est: « processus planifié qui permet aux adolescents et aux jeunes adultes atteints du VIH, ainsi qu'à leurs aidants, de disposer des connaissances et compétences nécessaires pour gérer leur santé de manière autonome ¼. La transition devrait débuter peu après la communication de la séropositivité et durer jusqu'à ce que l'adolescent ait acquis les connaissances et compétences nécessaires et qu'il souhaite passer à des services pour adultes, ou jusqu'à l'âge de 25 ans. Les éléments clés proposés de la transition sont: âges cibles pour le franchissement de certaines étapes; évaluation de la maturité; implication des aidants et communication avec les services pour adultes; possibilité de revenir à des services pédiatriques ou pour adolescents; transition de groupe; prise en compte des adolescents ayant des besoins spéciaux. Le continuum de soins, le lien entre les soins et la suppression virale sont d'importants marqueurs de la réussite de la transition. Les définitions et éléments clés proposés peuvent offrir un cadre pour structurer les programmes de transition dans d'autres pays.

La ampliación del acceso al diagnóstico y tratamiento del virus de la inmunodeficiencia humana (VIH) y la alta incidencia de la infección por el VIH en la adolescencia han dado lugar a una población creciente de adolescentes y adultos jóvenes que viven con el VIH. La prevalencia de una retención inadecuada en la atención, la supresión viral insuficiente y la pérdida de seguimiento son mayores entre los adolescentes y los adultos jóvenes en comparación con otros grupos de edad. Los resultados negativos pueden atribuirse a cambios psicosociales durante la adolescencia, pero también a una atención de transición deficiente de los servicios pediátricos a los servicios para adultos con VIH. En África subsahariana, los procesos de transición siguen siendo mal definidos y desestructurados, lo que puede suponer un riesgo para el cumplimiento y la retención del tratamiento. Describimos las definiciones existentes de transición y los marcos de transición, así como los elementos clave de la transición propuestos por las principales partes interesadas a nivel nacional en Kenia. Nuestra definición consensuada de transición es "un proceso planificado mediante el cual los adolescentes y adultos jóvenes que viven con el VIH, y sus cuidadores, son capacitados con conocimientos y habilidades que les permiten manejar su salud de manera independiente". La transición debe comenzar poco después de la revelación del estado serológico respecto al VIH hasta que el adolescente adquiera el conocimiento y las habilidades necesarias y esté dispuesto a trasladarse a los servicios para adultos, o a la edad de 25 años. Los elementos clave de la transición propuestos son: edades objetivo para el logro de los hitos; evaluación de la preparación; participación de los cuidadores y comunicación con las clínicas para adultos; flexibilidad para regresar a las clínicas para adolescentes o pediátricas; transición de grupos; y consideraciones para los adolescentes con necesidades especiales. La retención en la atención, la vinculación a la atención y la supresión viral son marcadores importantes del éxito de la transición. Las definiciones propuestas y los elementos clave podrían proporcionar un marco para estructurar los programas de transición en otros países.

Influence and involvement of support people in adolescent and young adult HIV testing.

HIV incidence and mortality are high among adolescents and young adults (AYA) in sub-Saharan Africa, but testing rates are low. Understanding how support people (SP), such as peers, partners, or parents, influence AYA may improve HIV testing uptake. AYA aged 14-24 seeking HIV testing at a referral hospital in Nairobi, Kenya completed a post-test survey assessing the role of SP. Among 1062 AYA, median age was 21. Overall, 12% reported their decision to test was influenced by a parent, 20% by a partner, and 22% by a peer. Young adults (20-24 years old) were more likely than adolescents (14-19 years old) to be influenced to test by partners (23% vs. 12%, p < .001), and less likely by parents (6.6% vs. 27%, p < .001), healthcare workers (11% vs. 16%, p < .05), or counselors (9.4% vs. 19%, p < .001). Half of AYA were accompanied for testing (9.9% with parent, 10% partner, 23% peer, 4.3% others, and 2.1% multiple types). Young adults were more likely than adolescents to present alone (58% vs. 32%, p < .001) or with a partner (12% vs. 6.7%, p < .05), and less likely with a parent (1.6% vs. 31%, p < .001). Similar proportions of adolescents and young adults came with a peer or in a group. Correlates of presenting with SP included: younger age (aRR = 1.55 [95%CI = 1.30-1.85]), female sex (aRR = 1.45 [95%CI = 1.21-1.73]), and school enrollment (aRR = 1.41 [95%CI = 1.05-1.88]). SP play an important role in AYAs' HIV testing and varies with age. Leveraging SP may promote uptake of HIV testing and subsequent linkage care for AYA.

Cofactors of Partner HIV Self-testing and Oral PrEP Acceptance Among Pregnant Women at High Risk of HIV in Kenya.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) and male partner HIV self-testing (HIVST) is being scaled up within antenatal clinics. Few data are available on how co-distribution influences acceptance of both interventions. METHODS: We used data from the PrEP Implementation of Mothers in Antenatal Care (NCT03070600) trial in Kenya. Women included in this analysis were determined to be at high risk of HIV and offered oral PrEP and partner HIVST. Characteristics were compared between women who chose: (1) PrEP and HIVST, (2) HIVST-alone, (3) PrEP-alone, or (4) declined both (reference), excluding women who had partners known to be living with HIV. RESULTS: Among 911 women, median age was 24 years, 87.3% were married, 43.9% perceived themselves to be at high risk of HIV and 13.0% had history of intimate partner violence (IPV). Overall, 68.9% accepted HIVST and 18.4% accepted PrEP, with 54.7% accepting HIVST-alone, 4.2% PrEP-alone, and 14.3% both HIVST and PrEP. Of women accepting HIVST, partner HIV testing increased from 20% to 82% and awareness of partner HIV status increased from 4.7% to 82.0% between pregnancy and 9 months postpartum (P < 0.001). Compared with women who accepted neither, choosing: (1) HIVST-alone was associated with being married, higher level of education, and residing with partner; (2) PrEP-alone was associated with lower social support, IPV, not residing with partner, longer time living with partner, and suspicion of other partners; and (3) PrEP and HIVST was associated with being married, IPV, and suspicion that partner had other partners. CONCLUSIONS: Understanding factors associated with accepting HIVST and PrEP can inform HIV prevention programs for pregnant women. CLINICAL TRIAL NUMBER: NCT03070600.

Development and validation of a prediction tool to support engagement in HIV care among young people ages 10-24 years in Kenya.

INTRODUCTION: Loss to follow-up (LTFU) among adolescents and young adults living with HIV (AYALWH) is a barrier to optimal health and HIV services. We developed and validated a clinical prediction tool to identify AYALWH at risk of LTFU. METHODS: We used electronic medical records (EMR) of AYALWH ages 10 to 24 in HIV care at 6 facilities in Kenya and surveys from a subset of participants. Early LTFU was defined as >30 days late for a scheduled visit in the last 6 months, which accounts for clients with multi-month refills. We developed a tool combining surveys with EMR ('survey-plus-EMR tool'), and an 'EMR-alone' tool to predict high, medium, and low risk of LTFU. The survey-plus-EMR tool included candidate sociodemographics, partnership status, mental health, peer support, any unmet clinic needs, WHO stage, and time in care variables for tool development, while the EMR-alone included clinical and time in care variables only. Tools were developed in a 50% random sample of the data and internally validated using 10-fold cross-validation of the full sample. Tool performance was evaluated using Hazard Ratios (HR), 95% Confidence Intervals (CI), and area under the curve (AUC) ≥ 0.7 for good performance and ≥0.60 for modest performance. RESULTS: Data from 865 AYALWH were included in the survey-plus-EMR tool and early LTFU was (19.2%, 166/865). The survey-plus-EMR tool ranged from 0 to 4, including PHQ-9 ≥5, lack of peer support group attendance, and any unmet clinical need. High (3 or 4) and medium (2) prediction scores were associated with greater risk of LTFU (high, 29.0%, HR 2.16, 95%CI: 1.25-3.73; medium, 21.4%, HR 1.52, 95%CI: 0.93-2.49, global p-value = 0.02) in the validation dataset. The 10-fold cross validation AUC was 0.66 (95%CI: 0.63-0.72). Data from 2,696 AYALWH were included in the EMR-alone tool and early LTFU was 28.6% (770/2,696). In the validation dataset, high (score = 2, LTFU = 38.5%, HR 2.40, 95%CI: 1.17-4.96) and medium scores (1, 29.6%, HR 1.65, 95%CI: 1.00-2.72) predicted significantly higher LTFU than low-risk scores (0, 22.0%, global p-value = 0.03). Ten-fold cross-validation AUC was 0.61 (95%CI: 0.59-0.64). CONCLUSIONS: Clinical prediction of LTFU was modest using the surveys-plus-EMR tool and the EMR-alone tool, suggesting limited use in routine care. However, findings may inform future prediction tools and intervention targets to reduce LTFU among AYALWH.

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.

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.

Implementation determinants and strategies in integration of PrEP into maternal and child health and family planning services: experiences of frontline healthcare workers in Kenya.

Background: Delivery of PrEP to adolescent girls and young women (AGYW) and to pregnant women through maternal and child health (MCH) and family planning (FP) clinics is scaling up in Kenya. Evaluation of implementation challenges and strategies is critical to optimize delivery. Methods: We conducted focus group discussions (FGDs) with healthcare workers (HCWs) in MCH and FP clinics offering PrEP in a large implementation project in Kisumu, Kenya. Discussion guides were based on the Consolidated Framework for Implementation Research (CFIR). FGDs were audio recorded and transcribed. Directed content analysis was used to identify implementation challenges and strategies to overcome them. Results: Fifty HCWs from 26 facilities participated in 8 FGDs. HCWs believed PrEP integration was appropriate because it met the needs of AGYW and pregnant women by providing a female-controlled prevention strategy and aligned with policy priorities of elimination of vertical HIV transmission. They were universally accepting of PrEP provision, especially through MCH clinics, noting the relative advantage of this approach because it: (1) enabled high coverage, (2) harmonized PrEP and MCH visits, and (3) minimized stigma compared to PrEP offered through HIV care clinics. However, HCWs noted implementation challenges affecting feasibility and adoption including: (1) increased workload and documentation burden amid workforce shortages, (2) insufficient health care worker knowledge (3) multiple implementing partners with competing priorities (4) drug and documentation form stockouts. HCWs employed various implementation strategies to overcome challenges, including task shifting from nurses to HIV testing providers, patient flow modifications (e.g., fast-tracking PrEP clients to reduce wait times), PrEP demand generation and myth clarification during health talks, provider education, dedicated PrEP delivery rooms, and coordination with adolescent-friendly services. Additional suggested strategies to improve PrEP integration included community education to increase broader PrEP awareness and enable shorter counseling sessions, and task-shifting data entry and client risk assessments. Conclusions: HCWs were enthusiastic about the appropriateness and acceptability of integrating PrEP services into MCH and FP clinics but noted challenges to adoption and feasibility. Strategies to address challenges focused on improving provider time and space constraints, and increasing provider and client knowledge.

'I feel that I should decide on my own .': who should be involved in the decision-making process for adolescent involvement in HIV research?

INTRODUCTION: Efforts to improve health outcomes among adolescents and young adults living with HIV (ALHs) are hampered by limited adolescent engagement in HIV-related research. We sought to understand the views of adolescents, caregivers and healthcare workers (HCWs) about who should make decisions regarding ALHs' research participation. METHODS: We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) with ALHs (aged 14-24 years), caregivers of ALHs and HCWs from six HIV care clinics in Western Kenya. We used semi-structured guides to explore ALHs' involvement in research decisions. Transcripts were analysed using thematic analysis; perspectives were triangulated between groups. RESULTS: We conducted 24 FGDs and 44 IDIs: 12 FGDs with ALHs, 12 with caregivers, and 44 IDIs with HCWs, involving 216 participants. HCWs often suggested that HIV research decision-making should involve caregivers and ALHs deciding together. In contrast, ALHs and parents generally thought decisions should be made individually, whether by HCWs/research teams (although this is likely ethically problematic), adolescents or caregivers. Caregiver and ALH preferences depended on ALHs' age, with younger ALHs requiring more support. A few caregivers felt that ALHs should consult with the research team/HCWs due to their greater knowledge of clinical care. ALHs emphasised that they should independently decide because they thought they had the right to do so and the capacity to consent. Poor communication and parental non-disclosure of HIV status influenced ALHs' views to exclude caregivers from decision-making. Regarding influences on research decision-making, ALHs were more willing to participate based on perceived contribution to science and less interested in participating in studies with potential risks, including loss of confidentiality. DISCUSSION: While research teams and HCWs felt that adolescents and caregivers should jointly make research decisions, ALHs and caregivers generally felt individuals should make decisions. As ALHs sometimes find caregiver support lacking, improving family dynamics might enhance research engagement.

"[T]he laws need to change to reflect current society": Insights from stakeholders involved in development, review or implementation of policies about adolescent consent for HIV testing, care and research in Kenya.

INTRODUCTION: Engaging adolescents in HIV care and research promotes the development of interventions tailored to their unique needs. Guidelines generally require parental permission for adolescents to receive HIV care/testing or participate in research, with exceptions. Nevertheless, parental permission requirements can restrict adolescent involvement in care and research. To better appreciate prospects for policy reform, we sought to understand the perspectives of stakeholders involved in the development, review and implementation of policies related to adolescents living with HIV. METHODS: Semi-structured individual interviews (IDIs) were conducted from October 2019 to March 2020 with 18 stakeholders with expertise in the (1) development of policy through membership in the Law Society of Kenya or work as a health policy official; (2) review of policy through ethics review committee service; or (3) implementation of policy through involvement in adolescent education. IDIs were conducted in English by Kenyan social scientists, audio-recorded and transcribed verbatim. We used thematic analysis to identify themes around how policies can be reformed to improve adolescent engagement in HIV care and research. RESULTS: Our analysis identified three major themes. First, policies should be flexible rather than setting an age of consent. Stakeholders noted that adolescents' capacity for engagement in HIV care and research depended on context, perceived risks and benefits, and "maturity"-and that age was a poor proxy for the ability to understand. Second, policies should evolve with changing societal views about adolescent autonomy. Participants recognized a generational shift in how adolescents learn and mature, suggesting the need for a more frequent review of HIV care and research guidelines. Third, adults should empower adolescent decision-making. Stakeholders felt that caregivers can gradually involve adolescents in decision-making to equip them to gain ownership over their health and lives, improving their confidence and capacity. CONCLUSIONS: Revising relevant laws to consider context, alternative measures of maturity, and evolving societal views about adolescence, along with supporting caregivers to assist in developing adolescent autonomy may promote more equitable and representative participation of adolescents in HIV care and research. Additional research should explore how to support caregivers and other adults to empower adolescents and improve stakeholder engagement in a more routine process of policy reform.

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.

Implementation of HIV Retesting During Pregnancy and Postpartum in Kenya: A Cross-Sectional Study.

INTRODUCTION: HIV retesting during pregnancy/postpartum can identify incident maternal HIV infection and prevent mother-to-child HIV transmission (MTCT). Guidelines recommend retesting HIV-negative peripartum women, but data on implementation are limited. We conducted a cross-sectional study in Kenya to measure the prevalence of maternal HIV retesting in programs and HIV incidence. METHODS: Programmatic HIV retesting data was abstracted from maternal and child health booklets among women enrolled in a cross-sectional and/or seeking services during pregnancy, delivery, or 9 months postpartum in Kenya between January 2017 and July 2019. Retesting was defined as any HIV test conducted by MTCT programs after the initial antenatal care test or conducted as part of retesting policies at/after delivery for women not tested during pregnancy. Poisson generalized linear regression was used to identify correlates of programmatic retesting among women enrolled at 9 months postpartum. RESULTS: Among 5,894 women included in the analysis, 3,124 only had data abstracted and 2,770 were enrolled in a cross-sectional study. Overall prevalence of programmatic HIV retesting was higher at 6 weeks (65%) and 9 months postpartum (72%) than in pregnancy (32%), at delivery (23%) and 6 months postpartum (28%) (P<.001 for all comparisons). HIV incidence was 0.72/100 person-years (PY) (95% confidence interval (CI)=0.43,1.22) in pregnancy and 0.23/100 PY (95% CI=0.09, 0.62) postpartum (incidence rate ratio: 3.09; 95% CI=0.97, 12.90; P=.02). CONCLUSION: Maternal retest coverage was high at 6 weeks and 9 months postpartum but low during pregnancy. Strategies to ensure high retesting coverage and detect women with incident maternal HIV infection are needed.

Higher prevalence of stunting and poor growth outcomes in HIV-exposed uninfected than HIV-unexposed infants in Kenya.

BACKGROUND: With the growing population of HIV-exposed uninfected (HEU) children globally, it is important to determine population-level growth differences between HEU and HIV-unexposed uninfected (HUU) children. METHODS: We analyzed data from a population-level survey enrolling mother-infant pairs attending 6-week and 9-month immunizations in 140 clinics across Kenya. Weight-for-age (WAZ), length-for-age (LAZ), head circumference-for-age (HCAZ) z-scores and underweight (WAZ < -2), stunting (LAZ < -2), and microcephaly (HCAZ < -2), were compared between HEU and HUU. Correlates of growth faltering and poor growth were assessed using generalized Poisson and linear regression models. RESULTS: Among 2457 infants, 456 (19%) were HEU. Among mothers living with HIV, 64% received antiretroviral therapy (ART) and 22% were on antiretroviral prophylaxis during pregnancy. At 9 months, 72% of HEU and 98% of HUU were breastfeeding. At 6 weeks, HEU had lower mean WAZ (-0.41 vs. -0.09; P < 0.001) and LAZ (-0.99 vs. -0.31; P = 0.001) than HUU. Stunting was higher in HEU than HUU at 6 weeks (34% vs. 18%, P < 0.001) and 9 months (20% vs. 10%, P < 0.001). In multivariable analyses, HEU had lower mean LAZ at 6 weeks (-0.67, 95% confidence interval [CI]: -1.07, -0.26) and 9 months (-0.57, 95% CI: -0.92, -0.21) and HEU had higher stunting prevalence (week-6 adjusted prevalence ratio [aPR]: 1.88, 95% CI: 1.35, 2.63; month-9 aPR: 2.10, 95% CI: 1.41, 3.13). HEU had lower mean head circumference (-0.49, 95% CI: -0.91, -0.07) and higher prevalence of microcephaly (aPR: 2.21, 95% CI: 1.11, 4.41) at 9 months. CONCLUSION: Despite high maternal ART coverage, HEU had poorer growth than HUU in this large population-level comparison. Optimizing breastfeeding practices in HEU may be useful to improve growth.

Transition to independent care for youth living with HIV: a cluster randomised clinical trial.

BACKGROUND: Transitioning youth living with HIV to adult care is a crucial step in the HIV care continuum; however, tools to support transition in sub-Saharan Africa are insufficient. We assessed the effectiveness of an adolescent transition package (ATP) to improve youth readiness for transition to independent HIV care. METHODS: In this hybrid type 1, multicentre, cluster randomised clinical trial, we assessed the effectiveness of an ATP (administered by routine clinic staff, which included standardised assessments and chapter books to guide discussions at scheduled clinic visits) in four counties in Kenya, with HIV clinics randomly assigned 1:1 to ATP or control (standard-of-care practice). Clinics were eligible to participate if they had at least 50 youth (aged 10-24 years) living with HIV enrolled in care. We used restricted randomisation to achieve cluster balance and an independent biostatistician used computer-generated random numbers to assign clinics. We excluded very large clinics with more than 1000 youth, clinics with fewer than 50 youth, paediatric-only clinics, clinics with logistical challenges, and the smallest clinics in Homa Bay county. Youth were eligible for the transition intervention if they were enrolled in participating clinics, were aged 15-24 years, and were aware of their positive HIV diagnosis. Study staff assessed transition readiness scores overall and by four domains (HIV literacy, self-management, communication, and support) in youth with HIV, which were then compared between groups by use of mixed-effects linear regression models. Analysis was by intention-to-treat and was adjusted for multiple comparisons. This trial is registered with ClinicalTrials.gov, NCT03574129. FINDINGS: We identified 35 clinics in four counties; of these, ten were assigned to the intervention group and ten to the control group. Of 1066 youth with HIV enrolled between Nov 1, 2019, and March 18, 2020, 578 (54%) were in intervention and 488 (46%) in control sites. Mean baseline transition readiness score was 12·1 (SD 3·4) in ATP sites and 11·4 (3·7) in control sites. At 1 year, adjusting for baseline scores, age, and months since HIV disclosure, participants in the ATP group had significantly higher overall transition readiness scores (adjusted mean difference 1·7, 95% CI 0·3-3·1, p=0·024), and higher scores in HIV literacy domain (adjusted mean difference 1·0, 0·2-1·7, p=0·011). At 12 months, 15 serious adverse events were recorded, none of which were thought to be related to study participation. INTERPRETATION: Integrating ATP approaches could enhance long-term HIV care in youth with HIV as they age into adulthood. FUNDING: US National Institutes of Health.

Brief Report: Pediatric Saliva-Based HIV Testing: Health care Worker and Caregiver Acceptability.

BACKGROUND: Pediatric HIV testing remains suboptimal. The OraQuick test [saliva-based test (SBT)] is validated in pediatric populations ≥18 months. Understanding caregiver and health care worker (HCW) acceptability of pediatric SBT is critical for implementation. METHODS: A trained qualitative interviewer conducted 8 focus group discussions (FGDs): 4 with HCWs and 4 with caregivers of children seeking health services in western Kenya. FGDs explored acceptability of pediatric SBT and home- and facility-based SBT use. Two reviewers conducted consensus coding and thematic analyses of transcripts using Dedoose. RESULTS: Most HCWs but few caregivers had heard of SBT. Before seeing SBT instructions, both had concerns about potential HIV transmission through saliva, which were mostly alleviated after kit demonstration. Noted benefits of SBT included usability and avoiding finger pricks. Benefits of facility-based pediatric SBT included shorter client waiting and service time, higher testing coverage, and access to HCWs, while noted challenges included ensuring confidentiality. Benefits of caregivers using home-based SBT included convenience, privacy, decreased travel costs, increased testing, easier administration, and child comfort. Perceived challenges included not receiving counseling, disagreements with partners, child neglect, and negative emotional response to a positive test result. Overall, HCWs felt that SBT could be used for pediatric HIV testing but saw limited utility for caregivers performing SBT without an HCW present. Caregivers saw utility in home-based SBT but wanted easy access to counseling in case of a positive test result. CONCLUSIONS: SBT was generally acceptable to HCWs and caregivers and is a promising strategy to expand testing coverage.