Comparison of Self and Caregiver Reports of Antiretroviral Treatment Adherence among Children and Adolescents Living with HIV in Western Kenya.

BACKGROUND: Youth living with HIV with perinatal infection spend a lifetime taking antiretroviral treatment (ART) to suppress the virus, and face significant challenges to successfully maintaining ART adherence. Tools to measure adherence include self-report, medication event monitoring system (MEMS) pill bottle caps, pill counts, and plasma or hair drug levels; however, the inter-rater agreement between child and caregiver self-report has not been validated in an African setting. This study aims to assess inter-rater agreement between child and caregiver self-reports, compared to reporting from MEMS pill bottle caps. METHODS: This was a secondary analysis of a cluster-randomized trial to evaluate an intervention for children living with HIV, conducted at the Academic Model Providing Access to Healthcare in western Kenya. We analyzed data from 285 child-caregiver dyads to compare adherence self-reported by children and their caregivers, and subsequently compared all self-reports to adherence reported by MEMS pill bottle caps to determine whether child or caregiver self-reports aligned more closely with adherence measured by MEMS. RESULTS: Children and their caregivers reported similar levels of adherence and numbers of missed doses in the past month, and both reports were similarly associated with adherence reported by MEMS pill bottle caps. Children with a caregiver that was not a biological parent were significantly more likely to report more missed doses than their caregiver. The correlation coefficient for the relationship between the child and caregiver self-reports was 0.71; for the relationship between child report and MEMS was 0.23; and for the relationship between caregiver report and MEMS was 0.20. Both children and caregivers under-reported non-adherence compared to MEMS data. CONCLUSION: Children and caregiver self-reports were generally similar in reporting adherence and were not highly correlated with MEMS reports of adherence, with children and caregivers reporting higher level of adherence than the MEMS data. This may indicate that children and caregiver reports are similarly inaccurate or biased; however, further research with larger sample sizes is required to further understand the differences in these reports.

Comparison of self-reported ART adherence rates among children and adolescents living with HIV in western Kenya The study aims to compare adherence between children and caregivers of Youth Living with HIV (YLWH) with perinatal infection, comparing data from 285 child-caregiver dyads and MEMS pill bottle caps. Results showed similar levels of adherence and missed doses in the past month, with a correlation coefficient of 0.71. However, children and caregivers reported higher levels of adherence than MEMS data. The study highlights the importance of understanding the reliability between self-reports and MEMS data in promoting adherence among YLWH.

Using Narrative Films to Combat HIV-Related Stigma in Western Kenya: An Exploratory Pilot Study of Adolescents Living With HIV and Their Caregivers.

Objective. Interventions that effectively address HIV-related stigma are urgently needed to improve outcomes for adolescents living with HIV (ALHIV). We piloted a series of 4 short narrative films depicting Kenyan ALHIV's lived experiences of stigma and discrimination with 57 ALHIV and 50 adult caregivers of ALHIV in western Kenya. Methods. Participants completed either pre- and post-viewing questionnaires, including an HIV/AIDS-related stigma and discrimination scale, or participated in post-viewing focus group discussions. Three-month follow-up visits were conducted. Results. Caregivers endorsed significantly greater disagreement with stigmatizing statements on the scale at 3-month follow-up, whereas adolescents had no significant differences in scores. Participants reported they believed the films would have a positive impact on their communities and had led to changes in their own attitudes, beliefs and/or behavior. Conclusion. The HIV Stigma Films may show promise as an intervention to reduce stigmatizing attitudes and beliefs about HIV-infection, especially among caregivers of ALHIV.

Ethical Considerations for Engaging Children and Adolescents Living with HIV in Research in African Countries: A Systematic Review.

Research engaging children and adolescents living with HIV (CALWH) is critical for youth-friendly services and HIV care, and researchers need to ensure that such engagement is ethical. We conducted a systematic review to identify key ethical considerations for the engagement of CALWH in research. The review focused on primary research articles conducted in African countries that examined ethical issues in CALWH engaged in research. Ten studies met the inclusion criteria; the following seven key domains were extracted: 1) justifications for engaging CALWH in research; 2) community involvement; 3) informed consent/assent; 4) caregiver involvement; 5) perceptions of benefits; 6) perception of the risks of involvement; and 7) confidentiality. These domains can inform the ethical engagement of CALWH in research.

Ethical Considerations for Engaging Youth Living with HIV in Research: Perspectives from Youth, Their Caregivers and Subject Matter Experts in Kenya.

Introduction: Engaging youth living with HIV (YLWH) in research is critical to improving HIV-related outcomes, but their involvement raises unaddressed bioethical questions. Methods: This study used qualitative inquiry with Kenyan YLWH, caregivers, and subject matter experts (SMEs) to evaluate ethical considerations and strategies for research involving YLWH. Results: Interviews were conducted with 99 participants: 40 YLWH (median age 17.5, 50% female), 20 caregivers (70% female), and 39 SMEs (44% female). All participant groups discussed the need for HIV disclosure status assessment, confidentiality, and engagement of caregivers. Youth participants discussed the importance of clear protocol explanations and developing good rapport. All participant groups perceived youth under 18 to be harder to recruit due to a number of identified barriers. Clinic settings were the most acceptable place for recruitment. Conclusion: Participants provided perspectives on engaging YLWH in research that can be incorporated into protocols and regulatory guidelines.

Added Value of Next Generation Sequencing in Characterizing the Evolution of HIV-1 Drug Resistance in Kenyan Youth.

Drug resistance remains a global challenge in children and adolescents living with HIV (CALWH). Characterizing resistance evolution, specifically using next generation sequencing (NGS) can potentially inform care, but remains understudied, particularly in antiretroviral therapy (ART)-experienced CALWH in resource-limited settings. We conducted reverse-transcriptase NGS and investigated short-and long-term resistance evolution and its predicted impact in a well-characterized cohort of Kenyan CALWH failing 1st-line ART and followed for up to ~8 years. Drug resistance mutation (DRM) evolution types were determined by NGS frequency changes over time, defined as evolving (up-trending and crossing the 20% NGS threshold), reverting (down-trending and crossing the 20% threshold) or other. Exploratory analyses assessed potential impacts of minority resistance variants on evolution. Evolution was detected in 93% of 42 participants, including 91% of 22 with short-term follow-up, 100% of 7 with long-term follow-up without regimen change, and 95% of 19 with long-term follow-up with regimen change. Evolving DRMs were identified in 60% and minority resistance variants evolved in 17%, with exploratory analysis suggesting greater rate of evolution of minority resistance variants under drug selection pressure and higher predicted drug resistance scores in the presence of minority DRMs. Despite high-level pre-existing resistance, NGS-based longitudinal follow-up of this small but unique cohort of Kenyan CALWH demonstrated continued DRM evolution, at times including low-level DRMs detected only by NGS, with predicted impact on care. NGS can inform better understanding of DRM evolution and dynamics and possibly improve care. The clinical significance of these findings should be further evaluated.

HIV-Related Stigma Shapes Research Participation for Youth Living With HIV in Kenya.

Introduction: HIV stigma affects medication adherence, psychosocial outcomes, and clinical management for youth living with HIV (YLWH). We explored the impact of HIV stigma on research participation, to inform the ethical engagement of this vulnerable group. Methods: We interviewed 40 YLWH, 20 caregivers, and 39 subject matter experts (SMEs); transcripts were analyzed by HK and EG, with emerging themes confirmed by JA and AC. Results: All categories of participants identified the impacts of stigma on YLWH research participation, suggesting implementing privacy protections, considering recruitment locations carefully, and developing supportive relationships with YLWH. SMEs suggested that YLWH experience uniquely high risks from stigma due to the compounding effects of developmental challenges and transitionary life period. Accidental HIV disclosure and subsequent stigma were identified as a risk of research participation; some viewed the creation of community through research as a benefit. Conclusion: Participants provided insights into stigma-related considerations for research with YLWH, which may guide engagement protocols.

Multi-media teacher training and HIV-related stigma among primary and secondary school teachers in Western Kenya.

ABSTRACTHIV stigma is associated with delayed HIV disclosure and worse clinical outcomes for adolescents living with HIV (ALWH). Teachers critically influence school environments, but are understudied in terms of HIV stigma. We implemented a school-level, cluster-randomized trial to assess the impact of a one-day multi-media training on the knowledge, attitudes and beliefs (K/A/B) of school teachers in western Kenya. Teachers' K/A/B were evaluated at baseline and six months. Additionally, we assessed stigma with ALWH enrolled in the included schools to explore the impact of the training. Teachers (N = 311) and ALWH (N = 19) were enrolled from 10 primary and 10 secondary schools. The intervention and control groups did not significantly differ in overall stigma score (mean 1.83 vs. 1.84; adjusted difference, 0.18 [95% CI, -0.082 to 0.045]) at six months; however, we found a trend towards improvement in overall stigma score and a significant difference in the community discrimination sub-scale among secondary school teachers (mean 3.02 vs. 3.19; adjusted difference, -0.166 [95% CI, -0.310 to -0.022]). ALWH reported few experiences of discrimination, but emphasized keeping their HIV status secret (84%). The teacher-training reduced secondary school teacher perceptions of community-level stigma, but did not impact individual attitudes or beliefs..

Real-Life Feasibility of HIV Drug Resistance Testing Using Dried Filter Analytes in Kenyan Children and Adolescents Living with HIV.

HIV-1 drug resistance remains a global challenge, yet access to testing is limited, particularly in resource-limited settings. We examined feasibility and limitations of genotyping using dried filter analytes in treatment-experienced Kenyan youth with HIV. Youth infected with HIV perinatally were enrolled in 2016-2018 at the Academic Model Providing Access to Healthcare in Eldoret, western Kenya. Samples were shipped in real-time at ambient temperature to the US, and those with viral load (VL)>1,000 copies/mL were tested based on convenience. Dried blood spots genotyping was attempted when unsuccessful from Hemaspots. Multiple logistic regression was used to examine predictors of genotyping success. Samples from 49 participants (median age 15 years, 43% female, median CD4 496 cells/µL [18%], median 8 years on therapy, median VL 11,827 copies/mL) were shipped after median 7 days from collection, arrived in 20 shipments after median 5 days, and extracted after median 2 days (1 day for samples processed on arrival; and 42 days for frozen Hemaspots). Overall, 29/49 (59%) samples with VL > 1,000 copies/mL and 25/32 (78%) with VL > 5,000 copies/mL were genotyped by either Hemaspots or DBS. Successful genotyping was associated with higher Hemaspot volume and higher VL. Real-life HIV-1 drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. Findings, particularly relevant where resistance testing is limited for clinical care, raise awareness to implementation practicability of this guidelines-recommended test in care of more individuals and populations. Further optimization of filter analytes is needed to overcome related challenges. IMPORTANCE In this manuscript we use dried filter analytes shipped from Kenya to the US in real time, to demonstrate the real-life feasibility of conducting HIV drug resistance testing in a vulnerable population of young children and adolescents with HIV in a resource limited setting. Such testing, which is recommended in resource-rich settings, is unavailable in most resource limited settings for individual clinical care. We show that real-life HIV drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. These findings raise awareness to the importance of HIV drug resistance for individual care, even in such settings, and emphasize the implementation practicability of this guidelines-recommended test.

HIV-1 Treatment Failure, Drug Resistance, and Clinical Outcomes in Perinatally Infected Children and Adolescents Failing First-Line Antiretroviral Therapy in Western Kenya.

BACKGROUND: Long-term impact of drug resistance in perinatally infected children and adolescents living with HIV (CALWH) is poorly understood. We determined drug resistance and examined its long-term impact on failure and mortality in Kenyan CALWH failing first-line non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART). SETTING: Academic Model Providing Access to Healthcare, western Kenya. METHODS: Participants were enrolled in 2010-2013 (timepoint 1) and a subsample re-enrolled after 4-7 years (timepoint 2). Viral load (VL) was performed on timepoint 1 samples, with genotyping of those with detectable VL. Primary endpoints were treatment failure (VL >1000 copies/mL) at and death before timepoint 2. Multinomial regression analysis was used to characterize resistance effect on death, failure, and loss-to-follow-up, adjusting for key variables. RESULTS: The initial cohort (n = 480) was 52% (n = 251) female, median age 8 years, median CD4% 31%, 79% (n = 379) on zidovudine/abacavir + lamivudine + efavirenz/nevirapine for median 2 years. Of these, 31% (n = 149) failed at timepoint 1. Genotypes at timepoint 1, available on n = 128, demonstrated 93% (n = 119) extensive resistance, affecting second line. Of 128, 22 failed at timepoint 2, 17 died, and 32 were lost to follow-up before timepoint 2. Having >5 resistance mutations at timepoint 1 was associated with higher mortality [relative risk ratio (RRR) = 8.7, confidence interval (CI) 2.1 to 36.3] and loss to follow-up (RRR = 3.2, CI 1.1 to 9.2). Switching to second line was associated with lower mortality (RRR <0.05, CI <0.05 to 0.1) and loss to follow-up (RRR = 0.1, CI <0.05 to 0.3). CONCLUSION: Extensive resistance and limited switch to second line in perinatally infected Kenyan CALWH failing first-line ART were associated with long-term failure and mortality. Findings emphasize urgency for interventions to sustain effective, life-long ART in this vulnerable population.

A Pilot Study of a Mobile Intervention to Support Mental Health and Adherence Among Adolescents Living with HIV in Western Kenya.

Mobile technologies represent potentially novel and scalable intervention delivery platforms for adolescents living with HIV (ALWH) in low- and middle-income countries. We conducted a prospective, mixed methods pilot study to evaluate the acceptability and feasibility of the WhatsApp® platform to deliver individual counseling services and facilitate peer support for ALWH in western Kenya. Thirty ALWH (17 female, mean age 15.4) on ART, engaged in HIV care and aware of their status, were enrolled. After 6 months, participants described their experiences with the intervention. Treatment adherence, stigma, and mental and behavioral health were assessed prospectively. Participants reported overall positive experiences and indicated that the platform encouraged peer network development. They endorsed potential benefits for treatment adherence, stigma reduction, and mental and behavioral health. All participants supported intervention expansion. In western Kenya, WhatsApp® was an acceptable and feasible platform for mobile counseling and peer support for ALWH.

A systematic review of interventions to reduce HIV-related stigma among primary and secondary school teachers.

HIV/AIDS-related stigma (HIV stigma) affects every aspect of adolescents' HIV management. Adolescents living with HIV (ALWH) are particularly vulnerable in schools where they have described experiencing HIV stigma. Teachers play a significant role in their students' lives. Stigmatizing attitudes or behaviors by teachers not only impact ALWH directly, but may influence the attitudes and behaviors of their peers. There is a dearth of literature exploring interventions to address HIV stigma in school-based settings. The objective of this review is to examine interventions to reduce HIV stigma among teachers globally. To conduct this systematic review, we used the PRISMA guidelines. Two articles met the inclusion criteria. Both eligible studies aimed to reduce HIV stigma among teachers or teachers in training through teacher training interventions in sub-Saharan Africa. The interventions included an interactive CD-ROM, a 2-day workshop, and peer facilitated workshops. Both studies demonstrated a significant decrease in HIV stigma in at least one study measure. Findings from this review are inconclusive. There is evidence to suggest that interventions can successfully decrease HIV stigma among teachers, but it is very limited. More research is needed in order to develop, implement, and evaluate stigma reducing interventions in the classroom.

Social Stigma Related to COVID-19 Disease Described by Primary and Secondary School Teachers and Adolescents Living With HIV in Western Kenya.

Introduction: Understanding community members' knowledge, attitudes, and beliefs about the novel SARS-CoV-2 virus and the prevalence of associated stigma are critical steps for increasing accurate public health knowledge, encouraging uptake of preventative or mitigating health behaviors, and ultimately bringing the COVID-19 pandemic under control. Methods: We conducted a one-time, phone-based assessment to assess the presence of perceived COVID-19 community stigma reported by Kenyan primary and secondary school teachers, as well as adolescents living with HIV. Participants were previously enrolled in an ongoing, cluster-randomized trial to evaluate the impact of multi-media teacher training on teachers' negative attitudes and beliefs around HIV. The SAFI Stigma Questionnaire, a validated tool to assess HIV-related stigma in this setting, was adapted to ask questions regarding the stigma and discrimination experienced or perceived during the COVID-19 pandemic. Results: We enrolled 330 participants in this study, including 311 primary and secondary teachers (56% female, average age 36 years) and 19 adolescents living with HIV (57.89% female, average age 16.37 years). None of the adolescent participants reported witnessing or experiencing discrimination related to COVID-19, nor did they report losing financial and/or social support. In contrast, the teacher participants reported prominent social stigma experiences of various levels and related to COVID-19. Teachers in the intervention group, who had completed the multi-media training on HIV-related stigma, were significantly less likely to think that the community viewed COVID-19 as a dirty or shameful disease, and less likely to feel it was important to keep their COVID-19 infection a secret, compared to the teacher control group. Conclusion: These findings suggest that COVID-19-related stigma may be prevalent in western Kenya and that interventions to reduce community-level stigma for HIV may also have a protective impact on other stigmatized infectious diseases such as COVID-19.

Perspectives of education sector stakeholders on a teacher training module to reduce HIV/AIDS stigma in Western Kenya.

BACKGROUND: For adolescents living with HIV (ALWH), school may be the most important but understudied social sphere related to HIV stigma. Teachers are role models in the classroom and within the community, and their attitudes and behavior towards people living with HIV may have critical psychosocial and treatment ramifications. Altering teachers' knowledge, attitudes and beliefs (K/A/B) about HIV could reduce the stigmatizing content within their teaching, classrooms and school, improving the environment for ALWH. METHODS: We developed a one-day teacher training module to enrich teacher K/A/B that included lecture presentations, HIV films and educational animation, structured instructions for teacher role play scenarios, and a question-and-answer session facilitated by a trained ALWH peer educator. We also conducted key informant interviews with education sector subject matter experts (SMEs), including education officers, county commissioners and head teachers to review and provide feedback on the teacher training module. RESULTS: We assembled an adolescent community advisory board and recruited 50 SMEs to review the training module and provide feedback. All SME participants stressed the importance and need for interventions to reduce stigma in the classroom, highlighting their own experiences observing stigmatizing behaviors in the community. The participants perceived the training as culturally relevant and easy to understand and had minor suggestions for improvement, including using image-based resources and brighter colors for ease of reading. All participants thought that the training should be expanded outside of the schools, as all people in a community have a role in the reduction of HIV stigma, and offered suggestions for other settings for implementation. CONCLUSION: Data from interviews with education sector stakeholders demonstrate that our process for developing a culturally appropriate multi-media intervention to reduce HIV stigma in the schools was feasible.

HIV-Related Knowledge, Attitudes, Behaviors and Experiences of Kenyan Adolescents Living with HIV Revealed in WhatsApp Group Chats.

INTRODUCTION: Mobile technologies represent a scalable platform for delivering knowledge and interventions targeting adolescents living with HIV (ALWH) in low and middle income countries. Data from mobile interventions can be used to assess the contextual understanding and experiences of ALWH. METHODS: We examined HIV-related knowledge, attitudes, beliefs, behaviors, and experiences of Kenyan ALWH revealed in the contextual data from enrollment in a WhatsApp® group chat intervention. RESULTS: Thirty ALWH (17 female, mean age 15.4) on ART, engaged in HIV care and aware of their status, were enrolled. Qualitative analysis of WhatsApp® chat discussions identified a gap in HIV knowledge, high medication-taking literacy, need for mental health support and significant barriers to adherence. Participants discussed challenges with HIV stigma and medication-taking in the school setting. CONCLUSION: These discussions demonstrate a need for education on HIV topics, mental health support for ALWH, and interventions for stigma mitigation in the school setting.