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.

HIV-1 drug resistance in children and adolescents remains a significant problem in countries facing the highest burden of the HIV epidemic. Surveillance of HIV-1 drug resistance in children and adolescents is an important public health strategy, particularly in resource-limited settings, and yet, it is limited due mostly to cost and infrastructure constraints.

Introduction: Adolescents living with HIV (ALHIV, ages 10–19) have developmentally specific needs in care, and have lower retention compared to other age groups. Family‐level contexts may be critical to adolescent HIV outcomes, but have often been overlooked. We investigated family‐level factors underlying disengagement and supporting re‐engagement among adolescents disengaged from HIV care.Methods: Semi‐structured interviews were performed with 42 disengaged ALHIV, 32 of their caregivers and 28 healthcare workers (HCW) in the Academic Model Providing Access to Healthcare (AMPATH) program in western Kenya, from 2018 to 2020. Disengaged ALHIV had ≥1 visit within the 18 months prior to data collection at one of two sites and nonattendance ≥60 days following their last scheduled appointment. HCW were recruited from 10 clinics. Transcripts were analysed through thematic analysis. A conceptual model for family‐level domains influencing adolescent HIV care engagement was developed from these themes.Results: Family‐level factors emerged as central to disengagement. ALHIV‐particularly those orphaned by the loss of one or both parents‐experienced challenges when new caregivers or unstable living situations limited support for HIV care. These challenges were compounded by anticipated stigma; resultant non‐disclosure of HIV status to household members; enacted stigma in the household, with overwhelming effects on adolescents; or experiences of multiple forms of trauma, which undermined HIV care engagement. Some caregivers lacked finances or social support to facilitate care. Others did not feel equipped to support adolescent engagement or adherence. Regarding facilitators to re‐engagement, participants described roles for household disclosure; and solidarity from caregivers, especially those also living with HIV. Family‐level domains influencing HIV care engagement were conceptualized as follows: (1) adolescent living situation and contexts; (2) household material resources or poverty; (3) caregiver capacities and skills to support adolescent HIV care; and (4) HIV stigma or solidarity at the household level.Conclusions: Family‐level factors are integral to retention in care for ALHIV. The conceptual model developed in this study for family‐level influences on care engagement may inform holistic approaches to promote healthy outcomes for ALHIV. Developmentally appropriate interventions targeting household relationships, disclosure, HIV stigma reduction, HIV care skills and resources, and economic empowerment may promote adolescent engagement in HIV care.

Introduction. Adolescents (10-19 years) living with HIV (ALWH) face unique challenges in controlling HIV long-term, including stigma and perception of stigma within their communities. Methods. We conducted a qualitative investigation of the sources of perceived HIV-related stigma with ALWH in western Kenya. Forty-six ALWH on ART, aware of their status, and engaged in care were enrolled. Interviews explored perceived stigma by probing the individuals and experiences that adolescents identify as causing or perpetuating their ongoing fears. Results. Participants (54% male, mean age 17.4) reported ongoing fears of stigmatization related to friends and peers not living with HIV. They described previous enacted and first-hand observations of stigma, most often occurring in pre-adolescence, by age mates or peers at school as the most common cause for their ongoing fears. Conclusions. Perceived stigma is prevalent among ALWH and develops from experiences in pre-adolescence. Anti-HIV stigma interventions addressing educators and children in school settings to combat perceived stigma at its source should be investigated.

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.

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.