Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986-2020.

BACKGROUND: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. METHODS: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. RESULTS: Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016-20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011-15), but dropped to 6.5% (2016-20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000-08], indicating propagation over 12 years. CONCLUSIONS: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.

Impact of the COVID-19 Pandemic on Persons Living with HIV in Western Washington: Examining Lived Experiences of Social Distancing Stress, Personal Buffers, and Mental Health.

Pandemic-related stressors may disproportionately affect the mental health of people with HIV (PWH). Stratified, purposive sampling was used to recruit 24 PWH who participated in a quantitative survey on COVID-19 experiences for in-depth interviews (IDIs). IDIs were conducted by Zoom, audio recorded and transcribed. Thematic analysis was used to develop an adapted stress-coping model. Participants experienced acute stress following exposure events and symptoms compatible with COVID-19. Social isolation and job loss were longer-term stressors. While adaptive coping strategies helped promote mental health, participants who experienced multiple stressors simultaneously often felt overwhelmed and engaged in maladaptive coping behaviors. Healthcare providers were important sources of social support and provided continuity in care and referrals to mental health and social services. Understanding how PWH experienced stressors and coped during the COVID-19 pandemic can help healthcare providers connect with patients during future public health emergencies, address mental health needs and support adaptive coping strategies.

Impact of the COVID-19 pandemic on mental health and viral suppression among persons living with HIV in western Washington.

The COVID-19 pandemic and social distancing measures elevated stress levels globally, exacerbating mental health challenges for people with HIV (PWH). We examined the effect of COVID-19-related stress on mental health among PWH in western Washington, exploring whether social support and coping self-efficacy were protective. Data on COVID-19-related stress, mental health, social support, and coping self-efficacy were collected using online surveys during the pandemic. Pre-COVID-19 mental health data were available for a subset of participants and were linked with the survey data. In the total sample (N = 373), COVID-19-stress was associated with elevated depression (PHQ-8, ß = 0.21, 95%CI [0.10, 0.32]) and anxiety (GAD-7, ß = 0.28, 95%CI [0.17, 0.39]). Among the subset of respondents with pre-pandemic mental health data (N = 103), COVID-19-related stress was associated with elevated PHQ-8 scores (ß = 0.35, 95%CI [0.15, 0.56]) and GAD-7 scores (ß = 0.35, 95%CI [0.16, 0.54]), adjusted for baseline mental health and other confounders. Coping self-efficacy was negatively associated with GAD-7 scores (ß = -0.01, 95%CI [-0.01, 0.00]), while social support was negatively associated with PHQ-8 scores (ß = -0.06, 95%CI [-0.12, -0.01]). Viral suppression before and during the pandemic did not differ among participants with available data. While COVID-19-related stress predicted elevated depression and anxiety symptoms among PWH, social support and coping self-efficacy were protective.

Key informant views on potential acceptability and feasibility of long-acting antiretroviral treatment for HIV in Kenya.

BACKGROUND: In 2020, 14% of diagnosed persons living with HIV (PLWH) in Kenya were not taking antiretroviral therapy (ART), and 19% of those on ART had unsuppressed viral loads. Long-acting antiretroviral therapy (LA-ART) may increase viral suppression by promoting ART uptake and adherence. We conducted key informant (KI) interviews with HIV experts in Kenya to identify product and delivery attributes related to the acceptability and feasibility of providing LA-ART to PLWH in Kenya. METHODS: Interviews were conducted via Zoom on potential LA-ART options including intra-muscular (IM) injections, subcutaneous (SC) injections, implants, and LA oral pills. KI were asked to discuss the products they were most and least excited about, as well as barriers and facilitators to LA-ART roll-out. In addition, they were asked about potential delivery locations for LA-ART products such as homes, pharmacies, and clinics. Interviews were recorded and transcribed, and data were analyzed using a combination of inductive and deductive coding. RESULTS: Twelve KI (5 women, 7 men) participated between December 2021 and February 2022. Overall, participants reported that LA-ART would be acceptable and preferable to PLWH because of fatigue with daily oral pills. They viewed IM injections and LA oral pills as the most exciting options to ease pill burden and improve adherence. KI felt that populations who could benefit most were adolescents in boarding schools and stigmatized populations such as sex workers. SC injections and implants were less favored, as they would require new training initiatives for patients or healthcare workers on administration. In addition, SC injections would require refrigeration and needle disposal after use. Some KI thought patients, especially men, might worry that IM injections and implants would impact fertility, given their role in family planning. Pharmacies were perceived by most KI as suboptimal delivery locations; however, given ongoing work in Kenya to include pharmacies in antiretroviral delivery, they recommended asking patients their views. CONCLUSION: There is interest and support for LA-ART in Kenya, especially IM injections and LA oral pills. Identifying patient preferences for modes and delivery locations and addressing misconceptions about specific products as they become available will be important before wide-scale implementation.

Inside a child's mind: The relations between mind wandering and executive function across 8- to 12-year-olds.

Mind wandering refers to attention oriented away from a current task to thoughts unrelated to the task, often resulting in poorer task performance. In adults, mind wandering is a common occurrence that is associated with the executive function facets of inhibitory control, working memory capacity, and task switching. In this study, we cross-sectionally examined whether the relation between mind wandering frequency and executive function changes across 8- to 12-year-old children. A total of 100 children completed three tasks targeting three facets of executive function. During each task, participants were occasionally prompted to report whether they were focused on the task or mind wandering. In examining the association between mind wandering frequency and executive function across the age range, we found a significant interaction between age and working memory capacity, such that it was negatively associated with mind wandering frequency only in 12-year-olds. This interaction with age was not significant for inhibitory control and task switching ability. Our results revealed differential relations between mind wandering and executive function facets, which vary with developmental stages. These findings highlight potential areas for targeted intervention to improve mind wandering regulation in children.

Characterizing the Communication Networks of Spanish- and English-Speaking Latinx Sexual Minority Men and Their Roles in Pre-Exposure Prophylaxis Uptake.

While pre-exposure prophylaxis (PrEP) has demonstrated efficacy in preventing HIV transmission, disparities in access persist in the United States, especially among Hispanic/Latinx sexual minority men (SMM). Language barriers and differences in how Latinx SMM obtain information may impact access to PrEP and HIV prevention. This study used data from the 2021 American Men's Internet Survey (AMIS) to examine differences in communication networks and PrEP use among Latinx SMM by primary language (Spanish vs. English). We examined the associations between Latinx SMM's individual- and meso-level communication networks and PrEP-related outcomes using modified Poisson regression with robust variances. Spanish-speaking Latinx SMM in the study were less likely to test for HIV, be aware of PrEP, and use daily PrEP, compared to English-speaking participants. Sexuality disclosure to a healthcare provider was positively associated with PrEP uptake among all participants and predicted STI testing over the past 12 months among English-speaking Latinx SMM. Findings highlight disparities in PrEP awareness and uptake among Latinx SMM, especially among those whose primary language is Spanish. Addressing these disparities through targeted interventions, including improved communication with healthcare providers, may help facilitate PrEP access and use in this population.

Designing an ECG curriculum for residents: Evidence-based approaches to improving resident ECG interpretation skills.

Residents enter their training with variable comfort and competency in electrocardiogram (ECG) interpretation. Accurately interpreting an ECG is a fundamental skill in medicine and resident physicians would benefit from a longitudinal, dedicated ECG curriculum as part of their training to enhance interpretation skills and improve patient outcomes. Educators currently employ a wide array of methodologies to teach their trainees proper ECG interpretation skills, with no single modality established as the gold-standard for teaching this crucial skill. We present evidence-based guidance on how educators may develop and implement an effective ECG interpretation curriculum as part of residency training.

Challenges with PrEP Uptake and Adherence Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kisumu, Kenya.

Data on challenges with pre-exposure prophylaxis (PrEP) uptake and adherence among Kenyan gay, bisexual, and other men who have sex with men (GBMSM) are limited. In this mixed-methods sequential explanatory design study, our quantitative phase followed 157 at-risk, HIV-negative GBMSM who accepted PrEP and enrolled in a cohort with 12-month follow-up. Stored dried blood spots collected at two intervals were batch tested for tenofovir diphosphate (TFV-DP) concentrations at study end. Despite high self-reported adherence, only 14.6% of individuals had protective TFV-DP levels at any visit. Protective TFV-DP levels were positively associated with injection drug use and a self-assessed moderate risk of acquiring HIV, and negatively associated with time since enrolment. In our subsequent qualitative phase, an intensive workshop was conducted with the GBMSM community to identify barriers and facilitators to PrEP uptake and adherence. These data revealed numerous challenges with traditional PrEP programs that must be addressed through community collaborations.

RESUMEN: La evidencia respecto a desafíos existentes con aceptación y adherencia de la profilaxis previa a la exposición (PrEP) de VIH, entre los hombres homosexuales, bisexuales y otros hombres que tienen sexo con hombres (GBMSM) en Kenia es limitada. Condujimos un estudio de métodos mixtos y diseño explicativo secuencial. En la fase cuantitativa seguimos a 157 GBMSM VIH-negativos en riesgo que aceptaron PrEP y se inscribieron en una cohorte con un seguimiento de 12 meses. Analizamos, por lotes y al final del estudio, gotas de sangre seca recolectada a dos intervalos de tiempo y previamente almacenada, para determinar las concentraciones de difosfato de tenofovir (TFV-DP). A pesar de la alta adherencia autoinformada, solo el 14,6% de las personas tenían niveles protectores de TFV-DP en alguna visita. Los niveles protectores de TFV-DP se asociaron positivamente con el uso de drogas inyectables y un riesgo moderado autoevaluado de contraer el VIH, y negativamente con el tiempo transcurrido desde la inscripción. En la fase cualitativa posterior, conversamos con GBMSM de la comunidad para identificar las barreras y los facilitadores para la concientización, aceptación, adherencia y retención a PrEP. Estos datos revelaron numerosos desafíos con los programas tradicionales de PrEP que deben abordarse mediante colaboraciones comunitarias.

The Effect of the Shikamana Peer-and-Provider Intervention on Depressive Symptoms, Alcohol Use, and Other Drug Use Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kenya.

Kenyan gay, bisexual, and other men who have sex with men (GBMSM) face stigma and discrimination, which may adversely impact mental health and limit antiretroviral therapy (ART) adherence among GBMSM living with HIV. We evaluated whether the Shikamana peer-and-provider intervention, which improved ART adherence among participants in a small randomized trial, was associated with changes in mental health or substance use. The intervention was associated with a significant decrease in PHQ-9 score between baseline and month 6 (estimated change - 2.7, 95% CI - 5.2 to - 0.2, p = 0.037) compared to standard care. In an exploratory analysis, each one-point increment in baseline HIV stigma score was associated with a - 0.7 point (95% CI - 1.3 to - 0.04, p = 0.037) greater decrease in PHQ-9 score over the study period in the intervention group. Additional research is required to understand factors that influence this intervention's effects on mental health outcomes.

Preschoolers modulate contrastive inferences during online language comprehension.

This study examined 4- and 5-year-olds' incremental interpretation of size adjectives, focusing on whether contrastive inferences are modulated by speaker behavior. Children (N = 120, 59 females, mostly White, tested between July, 2018 and August, 2019) encountered either a conventional or unconventional speaker who labeled objects in a correspondingly typical or atypical way. Critical utterances contained size adjectives (e.g., "Look at the big duck"). With conventional speakers, gaze measures indicated that children rapidly used the adjective to differentiate members of a contrasting pair, indicating that even 4-year-olds derive contrastive inferences. With unconventional speakers, contrastive inferences were delayed in processing. The findings demonstrate that preschoolers adjust their use of pragmatic cues when presented with evidence disconfirming their default assumptions about a speaker.

Five-year-olds' sensitivity to knowledge discrepancies about object identity during online language comprehension.

In everyday communication, children experience situations where their knowledge or perspectives differ from those of their communicative partner. The current study examined this issue in the context of real-time language comprehension, focusing on 5-year-old children's ability to manage knowledge discrepancies about the identity of mutually visible objects. In Experiment 1, we examined 5-year-olds' ability to manage privileged knowledge about an object's identity. Using a referential communication task, we tested children (N = 60) in either a shared knowledge condition, where both the child and the speaker knew the identity of a visually misleading object (e.g., a candle that looks like an apple), or a privileged knowledge condition, where only the child knew the identity of the visually misleading object. Of interest was whether children could suppress private knowledge while processing a phonologically related word (e.g., "Look at the candy"). Results showed that children did not inhibit this knowledge during the early moments of referential interpretation. In Experiment 2 (N = 30), we contrasted the privileged knowledge condition in Experiment 1 with the more traditional scenario used to test common ground use, where the child knows the speaker cannot see certain display objects. Results confirmed a stronger ability to manage discrepancies in the latter case. Together, the findings demonstrate differences in children's ability to manage distinct types of knowledge discrepancies during real-time language comprehension.

Transgender women in Kenya experience greater stigma, depressive symptoms, alcohol and drug use and risky sexual practices than cis-gendered men who have sex with men.

BACKGROUND: Worldwide, sexual and gender minority individuals have disproportionate burden of HIV. There are limited quantitative data from sub-Saharan Africa on the intersection of risks experienced by transgender women (TGW) in comparison to cis-men who have sex with men (MSM). This analysis addresses this gap by comparing reported stigma, psychosocial measures of health, and sexual risk practices between TGW and cis-MSM in Kenya. METHODS: We analyzed data from the baseline visit of an ongoing prospective cohort study taking place in three diverse metropolitan areas. Eligible participants were HIV-negative, assigned male at birth, ages 18-29 years, and reported anal intercourse in the past 3 months with a man or TGW. Data collected by audio computer assisted self-interview included sociodemographic measures, and sexual practices occurring in the past 3 months. Multivariable regressions assessed differences between TGW and cis-MSM in selected sexual practices, depressive symptoms, alcohol and drug use, and stigma. RESULTS: From September, 2019, through May, 2021, 838 participants were enrolled: 108 (12.9%) TGW and 730 (87.1%) cis-MSM. Adjusting for sociodemographic variables, TGW were more likely than cis-MSM to report: receptive anal intercourse (RAI; adjusted prevalence ratio [aPR] = 1.59, 95% CI: 1.32 - 1.92), engaging in group sex (aPR = 1.15, 95% CI: 1.04 - 1.27), 4 or more male sex partners (aPR = 3.31, 95% CI: 2.52 - 4.35), and 3 or more paying male sex partners (aPR = 1.58, 95% CI: 1.04 - 2.39). TGW were also more likely to report moderate to severe depressive symptoms (aPR = 1.42, 95% CI: 1.01 - 1.55), and had similar alcohol and drug abuse scores as cis-MSM. In sensitivity analysis, similar to TGW, male-identifying individuals taking feminizing gender affirming therapy had an increased likelihood of reporting RAI and group sex, and greater numbers of male sex partners and paying male sex partners relative to cis-MSM. CONCLUSIONS: Across three metropolitan areas in Kenya, TGW were more likely to report depressive symptoms and increased sexual risk taking. We identified a need for research that better characterizes the range of gender identities. Our analysis affirms the need for programmatic gender-affirming interventions specific to transgender populations in Kenya and elsewhere in Africa.

Implementation of a longitudinal, near-peer ECG didactic curriculum in an internal medicine residency program and impact on ECG interpretation skills.

BACKGROUND: To determine the impact of a longitudinal, near-peer, dedicated ECG didactic curriculum on internal medicine resident ability to accurately interpret ECGs. METHODS: This study employs a prospective cohort design. Internal medicine residents at University at Buffalo participated in monthly ECG didactic sessions over a 7-month period. Residents were invited to complete pre- and post-curriculum questionnaires. Responses were anonymous and participation voluntary. Data collected included basic demographics, career interest, exposure to clinical cardiology, and number of sessions attended. Residents were asked to interpret sixteen unique ECGs, divided evenly among eight common rhythms into both questionnaires. Pre- and post-curriculum cohorts were compared using t-tests and chi-square analyses. Associations between attendance, comfort level in interpretation, and number of correct interpretations were analyzed using Pearson correlations. Multivariate linear regression determined the strongest predictor of the number of correct ECG interpretations. RESULTS: The post-curriculum cohort correctly interpreted a significantly greater percentage of ECGs compared to pre-curriculum cohort (74.5% vs. 60.9%, p < .001). Didactic attendance was significantly associated with comfort level in interpreting ECGs (r = .328, p = .018) and trended towards an increased number of correct interpretations (r = .248, p = .077). Residents who attended three or more sessions demonstrated increased ECG interpretation skills compared to those who attended two or fewer sessions (80.0% vs. 71.1%, p = .048). Number of clinical cardiology rotations attended was significantly associated with correct interpretations (r = .310, p < .001) and was the strongest predictor of accurately interpreting ECGs (ß = 0.29, p = .037). CONCLUSIONS: Participation in a longitudinal, near-peer ECG didactic curriculum improved resident ability to interpret ECGs. A curriculum which contains both didactic sessions and clinical exposure may offer the greatest benefit in improving ECG interpretation skills.

Dynamics of HIV DNA reservoir seeding in a cohort of superinfected Kenyan women.

A reservoir of HIV-infected cells that persists despite suppressive antiretroviral therapy (ART) is the source of viral rebound upon ART cessation and the major barrier to a cure. Understanding reservoir seeding dynamics will help identify the best timing for HIV cure strategies. Here we characterize reservoir seeding using longitudinal samples from before and after ART initiation in individuals who sequentially became infected with genetically distinct HIV variants (superinfected). We previously identified cases of superinfection in a cohort of Kenyan women, and the dates of both initial infection and superinfection were determined. Six women, superinfected 0.2-5.2 years after initial infection, were subsequently treated with ART 5.4-18.0 years after initial infection. We performed next-generation sequencing of HIV gag and env RNA from plasma collected during acute infection as well as every ~2 years thereafter until ART initiation, and of HIV DNA from PBMCs collected 0.9-4.8 years after viral suppression on ART. We assessed phylogenetic relationships between HIV DNA reservoir sequences and longitudinal plasma RNA sequences prior to ART, to determine proportions of initial and superinfecting variants in the reservoir. The proportions of initial and superinfection lineage variants present in the HIV DNA reservoir were most similar to the proportions present in HIV RNA immediately prior to ART initiation. Phylogenetic analysis confirmed that the majority of HIV DNA reservoir sequences had the smallest pairwise distance to RNA sequences from timepoints closest to ART initiation. Our data suggest that while reservoir cells are created throughout pre-ART infection, the majority of HIV-infected cells that persist during ART entered the reservoir near the time of ART initiation. We estimate the half-life of pre-ART DNA reservoir sequences to be ~25 months, which is shorter than estimated reservoir decay rates during suppressive ART, implying continual decay and reseeding of the reservoir up to the point of ART initiation.

Stopping and restarting PrEP and loss to follow-up among PrEP-taking men who have sex with men and transgender women at risk of HIV-1 participating in a prospective cohort study in Kenya.

OBJECTIVE: To assess frequency and predictors of switching between being on and off PrEP and being lost to follow-up (LTFU) among men who have sex with men (MSM) and transgender women (TGW) with access to PrEP services in Sub-Saharan Africa. METHODS: This was a prospective cohort study of MSM and TGW from coastal Kenya who initiated daily oral PrEP from June 2017 to June 2019. Participants were followed monthly for HIV-1 testing, PrEP refill, risk assessment and risk reduction counselling. Follow-up was censored at the last visit before 30 June 2019, or the last HIV-1-negative visit (for those with HIV-1 seroconversion), whichever occurred first. We estimated transition intensities (TI) and predictors of switching: (i) between being off and on PrEP; and (ii) from either PrEP state and being LTFU (i.e. not returning to the clinic for > 90 days) using a multi-state Markov model. RESULTS: In all, 134 participants starting PrEP were followed for a median of 20.3 months [interquartile range (IQR): 7.7-22.1]. A total of 49 (36.6%) people stopped PrEP 73 times [TI = 0.6/person-year (PY), 95% confidence interval (CI): 0.5-0.7] and, of these, 25 (51.0%) restarted PrEP 38 times (TI = 1.2/PY, 95% CI: 0.9-1.7). In multivariable analysis, stopping PrEP was related to anal sex ≤ 3 months, substance-use disorder and travelling. Restarting PrEP was related to non-Christian or non-Muslim religion and travelling. A total of 54 participants were LTFU: on PrEP (n = 47, TI = 0.3/PY, 95% CI: 0.3-0.5) and off PrEP (n = 7, TI = 0.2/PY, 95% CI: 0.1-0.4). In multivariable analysis, becoming LTFU while on PrEP was associated with secondary education or higher, living in the area for ≤ 1 year, residence outside the immediate clinic area and alcohol-use disorder. CONCLUSIONS: Switching between being on and off PrEP or becoming LTFU while on PrEP was frequent among individuals at risk of HIV-1 acquisition. Alternative PrEP options (e.g. event-driven PrEP) may need to be considered for MSM and TGW with PrEP-taking challenges, while improved engagement with care is needed for all MSM and TGW regardless of PrEP regimen.

Effect of an opt-out point-of-care HIV-1 nucleic acid testing intervention to detect acute and prevalent HIV infection in symptomatic adult outpatients and reduce HIV transmission in Kenya: a randomized controlled trial.

BACKGROUND: In sub-Saharan Africa, adult outpatients with symptoms of acute infectious illness are not routinely tested for prevalent or acute HIV infection (AHI) when seeking healthcare. METHODS: Adult symptomatic outpatients aged 18-39 years were evaluated by a consensus AHI risk score. Patients with a risk score ≥ 2 and no previous HIV diagnosis were enrolled in a stepped-wedge trial of opt-out delivery of point-of-care (POC) HIV-1 nucleic acid testing (NAAT), compared with standard provider-initiated HIV testing using rapid tests in the observation period. The primary outcome was the number of new diagnoses in each study period. Generalized estimating equations with a log-binomial link and robust variance estimates were used to account for clustering by health facility. The trial is registered with ClinicalTrials.gov NCT03508908. RESULTS: Between 2017 and 2020, 13 (0.9%) out of 1374 participants in the observation period and 37 (2.5%) out of 1500 participants in the intervention period were diagnosed with HIV infection. Of the 37 newly diagnosed cases in the intervention period, two (5.4%) had AHI. Participants in the opt-out intervention had a two-fold greater odds of being diagnosed with HIV (odds ratio = 2.2, 95% confidence interval: 1.39-3.51) after adjustment for factors imbalanced across study periods. CONCLUSIONS: Among symptomatic adults aged 18-39 years targeted by our POC NAAT intervention, we identified one chronic HIV infection for every 40 patients and one AHI patient for every 750 patients tested. Although AHI yield was low in this population, routinely offered opt-out testing could diagnose twice as many patients as an approach relying on provider discretion.

The systematic development of attributes and levels for a discrete choice experiment of HIV patient preferences for long-acting antiretroviral therapies in the United States.

INTRODUCTION: Patient preferences for long-acting antiretroviral therapies (LA-ART) should inform development of regimens with optimal adherence and acceptability. We describe a systematic process used to identify attributes and levels for a discrete choice experiment (DCE) designed to elicit preferences for potential LA-ART options in the US. METHODS: Our approach was conducted in four stages: data collection, data reduction, removing inappropriate attributes, and optimizing wording. We started with 8 attributes defining potential LA-ART products based on existing literature and knowledge of products in development. We conducted 12 key informant interviews with experts in HIV treatment. The list of attributes, the set of plausible levels for each attribute, and restrictions on combinations of attribute levels were updated iteratively. RESULTS: Despite uncertainty about which products will become available, key informant discussions converged on 4 delivery modes (infusions and patches were not considered immediately feasible) and 6 additional attributes. Treatment effectiveness and frequency of clinical monitoring were dropped. Oral lead-in therapy was split into two attributes: pre-treatment time undetectable and pre-treatment negative reaction testing. We omitted product-specific systemic and local side effects. In addition to mode, the final set of attributes included: frequency of dosing; location of treatment; pain; pre-treatment time undetectable; pre-treatment negative reaction testing; and late-dose leeway. CONCLUSIONS: A systematic process successfully captured elements that are both feasible and relevant to evaluating the acceptability of potential LA-ART alternatives to patients.

"Your status cannot hinder you": the importance of resilience among adolescents engaged in HIV care in Kenya.

BACKGROUND: Approximately 40% of the 110,000 adolescents living with HIV (ALHIV) in Kenya have not achieved viral suppression. Despite the increasing availability of adolescent-friendly services, adolescents face barriers that impact ART adherence. This study aimed to identify key stigma-related barriers to ART adherence and strategies used by adolescents in overcoming these barriers. METHODS: Data were collected by LVCT Health, a Kenyan organization with a programmatic focus on HIV testing, prevention, and care. 122 participants were recruited from 3 clinical sites affiliated with LVCT Health in Nairobi, Kisumu, and Mombasa. In-depth interviews were conducted with ALHIV (n = 12). Focus group discussions were conducted with ALHIV (n = 5), peer leaders (n = 3), and adolescents receiving HIV services in community settings (AIC) irrespective of HIV status (n = 3). Interviews and focus groups were audio recorded, translated, and transcribed. Data were analyzed thematically, with a focus on stigma and resilience. RESULTS: While AIC primarily focused on adherence barriers and stigma, ALHIV and, to some extent, peer leaders, also identified resilience factors that helped overcome stigma. Four major themes emerged: 1) knowledge and future-oriented goals can drive motivation for ALHIV to remain healthy; 2) disclosure to others strengthens support systems for ALHIV; 3) medication-taking strategies and strategic disclosure can overcome adherence challenges in school; and 4) a supportive clinic environment promotes continuous adolescent engagement in HIV care. These concepts were used to develop a conceptual stigma/resilience model depicting how resilience moderates negative effects of stigma among ALHIV. CONCLUSIONS: This study demonstrates the positive effects of ALHIV resilience on ART adherence and illuminates how stigma impacts ALHIV differently depending on their resilience. Strengths-based interventions, focused on increasing resilience among ALHIV in Kenya, and more formal involvement of adolescent peers to bolster adolescent support, have the potential to improve ART adherence among ALHIV.

Predictors of testing history and new HIV diagnosis among adult outpatients seeking care for symptoms of acute HIV infection in coastal Kenya: a cross-sectional analysis of intervention participants in a stepped-wedge HIV testing trial.

BACKGROUND: HIV testing is the first step to stop transmission. We aimed to evaluate HIV testing history and new diagnoses among adult outpatients in Kenya aged 18-39 years seeking care for symptoms of acute HIV infection (AHI). METHODS: The Tambua Mapema Plus study, a stepped-wedge trial, enrolled patients presenting to care at six primary care facilities with symptoms of AHI for a targeted HIV-1 nucleic acid (NA) testing intervention compared with standard provider-initiated testing using rapid antibody tests. Intervention participants underwent a questionnaire and NA testing, followed by rapid tests if NA-positive. Multinomial logistic regression was used to analyse factors associated with never testing or testing > 1 year ago ("late retesting") relative to testing ≤ 1 year ago ("on-time testers"). Logistic regression was used to analyse factors associated with new diagnosis. All analyses were stratified by sex. RESULTS: Of 1,500 intervention participants, 613 (40.9%) were men. Overall, 250 (40.8%) men vs. 364 (41.0%) women were late retesters, and 103 (16.8%) men vs. 50 (5.6%) women had never tested prior to enrolment. Younger age, single status, lower education level, no formal employment, childlessness, sexual activity in the past 6 weeks, and > 1 sexual partner were associated with testing history among both men and women. Intimate partner violence > 1 month ago, a regular sexual partner, and concurrency were associated with testing history among women only. New diagnoses were made in 37 (2.5%) participants (17 men and 20 women), of whom 8 (21.6%) had never tested and 16 (43.2%) were late retesters. Newly-diagnosed men were more likely to have symptoms for > 14 days, lower education level and no religious affiliation and less likely to be young, single, and childless than HIV-negative men; newly-diagnosed women were more likely to report fever than HIV-negative women. Among men, never testing was associated with fivefold increased odds (95% confidence interval 1.4-20.9) of new diagnosis relative to on-time testers in adjusted analyses. CONCLUSION: Most new HIV diagnoses were among participants who had never tested or tested > 1 year ago. Strengthening provider-initiated testing targeting never testers and late retesters could decrease time to diagnosis among symptomatic adults in coastal Kenya. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03508908 registered on 26/04/2018.

Adaptation of a social vulnerability index for measuring social frailty among East African women.

BACKGROUND: The number of older women living with HIV in Africa is growing, and their health outcomes may be adversely impacted by social frailty, which reflects deficits in social resources that accumulate over the lifespan. Our objective was to adapt a Social Vulnerability Index (SVI) originally developed in Canada for use in a study of older women living with or without HIV infection in Mombasa, Kenya. METHODS: We adapted the SVI using a five-step process: formative qualitative work, translation into Kiswahili, a Delphi procedure, exploration of potential SVI items in qualitative work, and a rating and ranking exercise. Four focus group discussions (FGD) were conducted (three with women living with HIV and one with HIV-negative women), and two expert panels were constituted for this process. RESULTS: Themes that emerged in the qualitative work were physical impairment with aging, decreased family support, a turn to religion and social groups, lack of a financial safety net, mixed support from healthcare providers, and stigma as an added burden for women living with HIV. Based on the formative FGD, the expert panel expanded the original 19-item SVI to include 34 items. The exploratory FGD and rating and ranking exercise led to a final 16-item Kenyan version of the SVI (SVI-Kenya) with six domains: physical safety, support from family, group participation, instrumental support, emotional support, and financial security. CONCLUSIONS: The SVI-Kenya is a holistic index to measure social frailty among older women in Kenya, incorporating questions in multiple domains. Further research is needed to validate this adapted instrument.