Clinical Implications of HIV Treatment and Prevention for Polygamous Families in Kenya and Uganda: "My Co-Wife Is the One Who Used to Encourage Me".

Polygamy is the practice of marriage to multiple partners. Approximately 6-11% of households in Uganda and 4-11% of households in Kenya are polygamous. The complex families produced by polygamous marriage customs give rise to additional considerations for healthcare providers and public health messaging around HIV care. Using 27 in-depth, semi-structured qualitative interviews with participants in two studies in rural Kenya and Uganda, we analysed challenges and opportunities that polygamous families presented in the diagnosis, treatment and prevention of HIV, and provider roles in improving HIV outcomes in these families. Overall, prevention methods seemed more justifiable to families where co-wives live far apart than when all members live in the same household. In treatment, diagnosis of one member did not always lead to disclosure to other members, creating an adverse home environment; but sometimes diagnosis of one wife led not only to diagnosis of the other, but also to greater household support.

Clinical implications of HIV treatment and prevention for polygamous families in Kenya and UgandaPolygamy is the practice of marriage to multiple partners. Approximately 6-11% of households in Uganda and 4-11% of households in Kenya are polygamous. The complex families produced by polygamous marriage customs give rise to additional considerations for healthcare providers and public health messaging around HIV care.

Exploring HIV risk perception mechanisms among youth in a test-and-treat trial in Kenya and Uganda.

Understanding risk perception and risk-taking among youth can inform targeted prevention efforts. Using a health beliefs model-informed framework, we analysed 8 semi-structured, gender-specific focus group discussions with 93 youth 15-24 years old (48% male, 52% female), drawn from the SEARCH trial in rural Kenya and Uganda in 2017-2018, coinciding with the widespread introduction of PrEP. Highly connected social networks and widespread uptake of antiretrovirals shaped youth HIV risk perception. Amid conflicting information about HIV prevention methods, youth felt exposed to multiple HIV risk factors like the high prevalence of HIV, belief that people with HIV(PWH) purposefully infect others, dislike of condoms, and doubts about PrEP efficacy. Young women also reported minimal sexual autonomy in the context of economic disadvantages, the ubiquity of intergenerational and transactional sex, and peer pressure from other women to have many boyfriends. Young men likewise reported vulnerability to intergenerational sex, but also adopted a sexual conquest mentality. Comprehensive sexuality education and economic empowerment, through credible and trusted sources, may moderate risk-taking. Messaging should leverage youth's social networks to spread fact-based, gender- and age-appropriate information. PrEP should be offered alongside other reproductive health services to address both pregnancy concerns and reduce HIV risk.

Randomized Trial of Dynamic Choice HIV Prevention at Antenatal and Postnatal Care Clinics in Rural Uganda and Kenya.

BACKGROUND: Pregnant and postpartum women in Sub-Saharan Africa are at high risk of HIV acquisition. We evaluated a person-centered dynamic choice intervention for HIV prevention (DCP) among women attending antenatal and postnatal care. SETTING: Rural Kenya and Uganda. METHODS: Women (aged 15 years or older) at risk of HIV acquisition seen at antenatal and postnatal care clinics were individually randomized to DCP vs. standard of care (SEARCH; NCT04810650). The DCP intervention included structured client choice of product (daily oral pre-exposure prophylaxis or postexposure prophylaxis), service location (clinic or out of facility), and HIV testing modality (self-test or provider-administered), with option to switch over time and person-centered care (phone access to clinician, structured barrier assessment and counseling, and provider training). The primary outcome was biomedical prevention coverage-proportion of 48-week follow-up with self-reported pre-exposure prophylaxis or postexposure prophylaxis use, compared between arms using targeted maximum likelihood estimation. RESULTS: Between April and July 2021, we enrolled 400 women (203 intervention and 197 control); 38% were pregnant, 52% were aged 15-24 years, and 94% reported no pre-exposure prophylaxis or postexposure prophylaxis use for ≥6 months before baseline. Among 384/400 participants (96%) with outcome ascertained, DCP increased biomedical prevention coverage 40% (95% CI: 34% to 47%; P < 0.001); the coverage was 70% in intervention vs. 29% in control. DCP also increased coverage during months at risk of HIV (81% in intervention, 43% in control; 38% absolute increase; 95% CI: 31% to 45%; P < 0.001). CONCLUSION: A person-centered dynamic choice intervention that provided flexibility in product, testing, and service location more than doubled biomedical HIV prevention coverage in a high-risk population already routinely offered access to biomedical prevention options.

Community-Wide Universal Human Immunodeficiency Virus (HIV) Test and Treat Intervention Reduces Tuberculosis Transmission in Rural Uganda: A Cluster-Randomized Trial.

BACKGROUND: Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. METHODS: In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. RESULTS: Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. CONCLUSIONS: A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.

Dynamic choice HIV prevention intervention at outpatient departments in rural Kenya and Uganda.

OBJECTIVE: HIV prevention service delivery models that offer product choices, and the option to change preferences over time, may increase prevention coverage. Outpatient departments in sub-Saharan Africa diagnose a high proportion of new HIV infections, but are an understudied entry point to biomedical prevention. DESIGN: Individually randomized trial of dynamic choice HIV prevention (DCP) intervention vs. standard-of-care (SOC) among individuals with current/anticipated HIV exposure risk at outpatient departments in rural Kenya and Uganda (SEARCH; NCT04810650). METHODS: Our DCP intervention included 1) product choice (oral preexposure prophylaxis [PrEP] or postexposure prophylaxis [PEP]) with an option to switch over time, 2) HIV provider- or self-testing, 3) service location choice (community vs. clinic-based), and 4) provider training on patient-centered care. Primary outcome was proportion of follow-up covered by PrEP/PEP over 48 weeks assessed via self-report. RESULTS: We enrolled 403 participants (61% women; median 27 years, IQR 22-37). In the DCP arm, 86% ever chose PrEP, 15% ever chose PEP over 48 weeks; selection of HIV self-testing increased from 26 to 51% and of out-of-facility visits from 8 to 52%. Among 376 of 403 (93%) with outcomes ascertained, time covered by PrEP/PEP was higher in DCP (47.5%) vs. SOC (18.3%); difference = 29.2% (95% confidence interval: 22.7-35.7; P  < 0.001). Effects were similar among women and men (28.2 and 31.0% higher coverage in DCP, respectively) and larger during periods of self-reported HIV risk (DCP 64.9% vs. SOC 26.3%; difference = 38.6%; 95% confidence interval: 31.0-46.2; P  < 0.001). CONCLUSION: A dynamic choice HIV prevention intervention resulted in two-fold greater time covered by biomedical prevention products compared to SOC in general outpatient departments in eastern Africa.

Randomized Trial of a "Dynamic Choice" Patient-Centered Care Intervention for Mobile Persons With HIV in East Africa.

BACKGROUND: Persons with HIV (PWH) with high mobility face obstacles to HIV care engagement and viral suppression. We sought to understand whether a patient-centered intervention for mobile PWH would improve viral suppression and retention in care, and if so, which subgroups would benefit most. METHODS: In a randomized trial, we evaluated the effect of an intervention designed to address barriers to care among mobile (≥2 weeks out of community in previous year) PWH with viral nonsuppression or recent missed visits in Kenya and Uganda (NCT04810650). The intervention included dynamic choice of a "travel pack" (emergency antiretroviral therapy [ART] supply, discrete ART packaging, and travel checklist), multimonth and offsite refills, facilitated transfer to out-of-community clinics, and hotline access to a mobility coordinator. The primary outcome was viral suppression (<400 copies/mL) at 48 weeks. Secondary outcomes included retention in care and ART possession. RESULTS: From April 2021 to July 2022, 201 participants were enrolled and randomized (102 intervention, 99 control): 109 (54%) were female participants and 101 (50%) from Kenya; median age was 37 years (interquartile range: 29-43). At 48 weeks, there was no significant difference in viral suppression in intervention (85%) vs. control (86%). The intervention improved retention in care (risk ratio: 1.06[1.02-1.1]; P < 0.001) and ART possession (risk ratio: 1.07[1.03-1.11]; P < 0.001), with larger effect sizes among persons with baseline nonsuppression and high mobility (≥2 weeks out of community in previous 3 months). CONCLUSIONS: Mobile PWH-centered care should be considered for high-risk mobile populations, including nonsuppressed and highly mobile PWH, to improve retention in care and sustain viral suppression over time. TRIAL REGISTRATION: NCT04810650.

A community-based dynamic choice model for HIV prevention improves PrEP and PEP coverage in rural Uganda and Kenya: a cluster randomized trial.

INTRODUCTION: Optimizing HIV prevention may require structured approaches for providing client-centred choices as well as community-based entry points and delivery. We evaluated the effect of a dynamic choice model for HIV prevention, delivered by community health workers (CHWs) with clinician support, on the use of biomedical prevention among persons at risk of HIV in rural East Africa. METHODS: We conducted a cluster randomized trial among persons (≥15 years) with current or anticipated HIV risk in 16 villages in Uganda and Kenya (SEARCH; NCT04810650). The intervention was a client-centred HIV prevention model, including (1) structured client choice of product (pre-exposure prophylaxis [PrEP] or post-exposure prophylaxis [PEP]), service location (clinic or out-of-clinic) and HIV testing modality (self-test or rapid test), with the ability to switch over time; (2) a structured assessment of patient barriers and development of a personalized support plan; and (3) phone access to a clinician 24/7. The intervention was delivered by CHWs and supported by clinicians who oversaw PrEP and PEP initiation and monitoring. Participants in control villages were referred to local health facilities for HIV prevention services, delivered by Ministry of Health staff. The primary outcome was biomedical prevention coverage: a proportion of 48-week follow-up with self-reported PrEP or PEP use. RESULTS: From May to July 2021, we enrolled 429 people (212 intervention; 217 control): 57% women and 35% aged 15-24 years. Among intervention participants, 58% chose PrEP and 58% chose PEP at least once over follow-up; self-testing increased from 52% (baseline) to 71% (week 48); ≥98% chose out-of-facility service delivery. Among 413 (96%) participants with the primary outcome ascertained, average biomedical prevention coverage was 28.0% in the intervention versus 0.5% in the control: a difference of 27.5% (95% CI: 23.0-31.9%, p<0.001). Impact was larger during periods of self-reported HIV risk: 36.6% coverage in intervention versus 0.9% in control, a difference of 35.7% (95% CI: 27.5-43.9, p<0.001). Intervention effects were seen across subgroups defined by sex, age group and alcohol use. CONCLUSIONS: A client-centred dynamic choice HIV prevention intervention, including the option to switch between products and CHW-based delivery in the community, increased biomedical prevention coverage by 27.5%. However, substantial person-time at risk of HIV remained uncovered.

Effect of a brief alcohol counselling intervention on HIV viral suppression and alcohol use among persons with HIV and unhealthy alcohol use in Uganda and Kenya: a randomized controlled trial.

INTRODUCTION: Unhealthy alcohol use significantly contributes to viral non-suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub-Saharan Africa (SSA). METHODS: As part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills-based alcohol intervention among PWH with self-reported unhealthy alcohol use (Alcohol Use Disorders Identification Test-Consumption [AUDIT-C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non-suppression, defined as either recent HIV viral non-suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3-month in-person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (<400 copies/ml) at 24 weeks, and the secondary outcome was unhealthy alcohol use, defined by AUDIT-C or phosphatidylethanol (PEth), an alcohol biomarker, ≥50 ng/ml at 24 weeks. RESULTS: Between April and September 2021, 401 persons (198 intervention, 203 control) were enrolled from HIV clinics in Uganda (58%) and Kenya (27%) and alcohol-serving venues in Kenya (15%). At baseline, 60% were virally suppressed. Viral suppression did not differ between arms at 24 weeks: suppression was 83% in intervention and 82% in control arms (RR: 1.01, 95% CI: 0.93-1.1). Among PWH with baseline viral non-suppression, 24-week suppression was 73% in intervention and 64% in control arms (RR 1.15, 95% CI: 0.93-1.43). Unhealthy alcohol use declined from 98% at baseline to 73% in intervention and 84% in control arms at 24 weeks (RR: 0.86, 95% CI: 0.79-0.94). Effects on unhealthy alcohol use were stronger among women (RR 0.70, 95% CI: 0.56-0.88) than men (RR 0.93, 95% CI: 0.85-1.01) and among participants with a baseline PEth⩽200 ng/ml (RR 0.68, 95% CI: 0.53-0.87) versus >200 ng/ml (RR 0.97, 95% CI: 0.92-1.02). CONCLUSIONS: In a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non-suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV-associated co-morbidities.

Improving care engagement for mobile people living with HIV in rural western Kenya.

BACKGROUND: Antiretroviral therapy (ART) assures major gains in health outcomes among people living with HIV, however, this benefit may not be realized by all due to care interruptions. Mobile populations comprise a subgroup that is likely to have sub-optimal care engagement, resulting in discontinuation of ART. We sought to evaluate the barriers to care engagement among highly mobile individuals living with HIV and explore options aimed at improving engagement in care for this group. METHODS: Qualitative in-depth interviews were conducted in 2020 among a purposive sample of twelve persons living with HIV and eight health care providers in western Kenya, within a mixed methods study of mobility in communities participating in the SEARCH trial (NCT01864603). We explored the barriers to care engagement among mobile individuals living with HIV and explored different options aimed at enhancing care engagement. These included options such as a coded card containing treatment details, alternative drug packaging to conceal drug identity, longer refills to cover travel period, wrist bands with data storage capability to enable data transfer and "warm handoff" by providers to new clinics upon transfer. Data were inductively analyzed to understand the barriers and acceptability of potential interventions to address them. RESULTS: Stigma and lack of disclosure, rigid work schedules, and unpredictability of travel were major barriers to care engagement for highly mobile individuals living with HIV. Additionally, lack of flexibility in clinic schedules and poor provider attitude were identified as health-system-associated barriers to care engagement. Options that enhance flexibility, convenience and access to care were viewed as the most effective means of addressing the barriers to care by both patients and providers. The most preferred option was a coded card with treatment details followed by alternative drug packaging to conceal drug identity due to stigma and longer refills to cover travel periods. CONCLUSION: Highly mobile individuals living with HIV desire responsive, flexible, convenient and patient-centered care delivery models to enhance care engagement. They embraced simple health delivery improvements such as coded cards, alternative drug packaging and longer refills to address challenges of mobility.

Geographic Mobility and HIV Care Engagement among People Living with HIV in Rural Kenya and Uganda.

INTRODUCTION: Human mobility is a critical aspect of existence and survival, but may compromise care engagement among people living with HIV (PLHIV). We examined the association between various forms of human mobility with retention in HIV care and antiretroviral treatment (ART) interruptions. METHODS: In a cohort of adult PLHIV in Kenya and Uganda, we collected surveys in 2016 about past 6-month travel and lifetime migration histories, including reasons and locations, and engagement in HIV care defined as (1) discontinuation of care, and (2) history of a treatment interruption among those who remained in care. We estimated associations between mobility and these care engagement outcomes via logistic regression, adjusted for sex, prior mobility, age, region, marital status, household wealth, and education. RESULTS: Among 1081 participants, 56 (5%) reported having discontinued care; among those in care, 104 (10%) reported treatment interruption. Past-year migration was associated with a higher risk of discontinuation of care (adjusted odds ratio [aOR] 1.98, 95% CI 1.08-3.63). In sex-stratified models, the association was somewhat attenuated in women, but remained robust among men. Past-year migration was associated with reduced odds of having a treatment interruption among men (aOR 0.51, 95% CI 0.34-0.77) but not among women (aOR 2.67, 95% CI 0.78, 9.16). Travel in the past 6 months was not associated with discontinuation of care or treatment interruptions. CONCLUSIONS: We observed both negative and protective effects of recent migration on care engagement and ART use that were most pronounced among men in this cohort. Migration can break ties to ongoing care, but for men, who have more agency in the decision to migrate, may foster new care and treatment strategies. Strategies that enable health facilities to support individuals throughout the process of transferring care could alleviate the risk of care disengagement.

Navigating antiretroviral adherence in boarding secondary schools in Nairobi, Kenya: A qualitative study of adolescents living with HIV, their caregivers and school nurses.

In Kenya, adolescents spend much of their formative years in boarding secondary schools, which presents a challenging environment for antiretroviral (ART) adherence support among adolescents living with HIV (ALHIV). We examined the experiences of ALHIV, caregivers of adolescents, and school nurses regarding navigating ART adherence in boarding secondary schools. Between July and November 2022, we conducted focus group discussions (FGDs) among ALHIV attending boarding schools in Nairobi, Kenya, and caregivers of ALHIV, and in-depth interviews (IDIs) with school nurses. Clinic records were used to identify ALHIV and caregivers, who were invited to participate based on their availability. We categorized boarding schools into national, county, and sub-county levels and selected two schools from each category. We obtained permission from head teachers and invited school nurses to take part in virtual IDIs. The interviews were audio-recorded, transcribed verbatim, and analyzed thematically. We conducted two FGDs with 11 caregivers, two FGDs with 18 adolescents, and 7 IDIs with school nurses. Most of the ALHIV reported having disclosed their HIV status to a school nurse or teacher during admission. School nurse friendliness, being understanding, fair, and confidential were qualities associated with ALHIV willingness to confide in them. Strategies ALHIV used to adhere to medication included: waiting until students were engaged in other activities, waking up early, stepping away from others, and stating their drugs were for different ailments. Caregivers were nervous about school-based adherence counseling, fearing it could lead to inadvertent disclosure of adolescents' HIV status and stigmatization by fellow students. All school nurses reported lacking appropriate training in HIV adherence counseling for adolescents. ALHIV have devised innovative strategies to navigate pill-taking and enlist quiet support while operating in stigmatized school environments. Establishment of a strong school nurse-adolescent rapport and building nurses' skills are key to improving school-based support for ALHIV.

A multilevel health system intervention for virological suppression in adolescents and young adults living with HIV in rural Kenya and Uganda (SEARCH-Youth): a cluster randomised trial.

BACKGROUND: Social and cognitive developmental events can disrupt care and medication adherence among adolescents and young adults living with HIV in sub-Saharan Africa. We hypothesised that a dynamic multilevel health system intervention helping adolescents and young adults and their providers navigate life-stage related events would increase virological suppression compared with standard care. METHODS: We did a cluster randomised, open-label trial of young individuals aged 15-24 years with HIV and receiving care in eligible clinics (operated by the government and with ≥25 young people receiving care) in rural Kenya and Uganda. After clinic randomisation stratified by region, patient population, and previous participation in the SEARCH trial, participants in intervention clinics received life-stage-based assessment at routine visits, flexible clinic access, and rapid viral load feedback. Providers had a secure mobile platform for interprovider consultation. The control clinics followed standard practice. The primary, prespecified endpoint was virological suppression (HIV RNA <400 copies per mL) at 2 years of follow-up among participants who enrolled before Dec 1, 2019, and received care at the study clinics. This trial is registered with ClinicalTrials.gov, NCT03848728, and is closed to recruitment. FINDINGS: 28 clinics were enrolled and randomly assigned (14 control, 14 intervention) in January, 2019. Between March 14, 2019, and Nov 26, 2020, we recruited 1988 participants at the clinics, of whom 1549 were included in the analysis (785 at intervention clinics and 764 at control clinics). The median participant age was 21 years (IQR 19-23) and 1248 (80·6%) of 1549 participants were female. The mean proportion of participants with virological suppression at 2 years was 88% (95% CI 85-92) for participants in intervention clinics and 80% (77-84) for participants in control clinics, equivalent to a 10% beneficial effect of the intervention (risk ratio [RR] 1·10, 95% CI 1·03-1·16; p=0·0019). The intervention resulted in increased virological suppression within all subgroups of sex, age, and care status at baseline, with greatest improvement among those re-engaging in care (RR 1·60, 95% CI 1·00-2·55; p=0·025). INTERPRETATION: Routine and systematic life-stage-based assessment, prompt adherence support with rapid viral load testing, and patient-centred, flexible clinic access could help bring adolescents and young adults living with HIV closer towards a goal of universal virological suppression. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health.

Uptake of a patient-centred dynamic choice model for HIV prevention in rural Kenya and Uganda: SEARCH SAPPHIRE study.

INTRODUCTION: Person-centred HIV prevention delivery models that offer structured choices in product, testing and visit location may increase coverage. However, data are lacking on the actual uptake of choices among persons at risk of HIV in southern Africa. In an ongoing randomized study (SEARCH; NCT04810650) in rural East Africa, we evaluated the uptake of choices made when offered in a person-centred, dynamic choice model for HIV prevention. METHODS: Using the PRECEDE framework, we developed a persont-centred, Dynamic Choice HIV Prevention (DCP) intervention for persons at risk of HIV in three settings in rural Kenya and Uganda: antenatal clinic (ANC), outpatient department (OPD) and in the community. Components include: provider training on product choice (predisposing); flexibility and responsiveness to client desires and choices (pre-exposure prophylaxis [PrEP]/post-exposure prophylaxis [PEP], clinic vs. off-site visits and self- or clinician-based HIV testing) (enabling); and client and staff feedback (reinforcing). All clients received a structured assessment of barriers with personalized plans to address them, mobile phone access to clinicians (24 hours/7 days/week) and integrated reproductive health services. In this interim analysis, we describe the uptake of choices of product, location and testing during the first 24 weeks of follow-up (April 2021-March 2022). RESULTS: A total of 612 (203 ANC, 197 OPD and 212 community) participants were randomized to the person-centred DCP intervention. We delivered the DCP intervention in all three settings with diverse populations: ANC: 39% pregnant; median age: 24 years; OPD: 39% male, median age 27 years; and community: 42% male, median age: 29 years. Baseline choice of PrEP was highest in ANC (98%) vs. OPD (84%) and community (40%); whereas the proportion of adults selecting PEP was higher in the community (46%) vs. OPD (8%) and ANC (1%). Personal preference for off-site visits increased over time (65% at week 24 vs. 35% at baseline). Interest in alternative HIV testing modalities grew over time (38% baseline self-testing vs. 58% at week 24). CONCLUSIONS: A person-centred model incorporating structured choice in biomedical prevention and care delivery options in settings with demographically diverse groups, in rural Kenya and Uganda, was responsive to varying personal preferences over time in HIV prevention programmes.

Universal HIV Testing and Treatment With Patient-Centered Care Improves ART Uptake and Viral Suppression Among Adults Reporting Hazardous Alcohol Use in Uganda and Kenya.

OBJECTIVES: Determine whether patient-centered, streamlined HIV care achieves higher antiretroviral therapy (ART) uptake and viral suppression than the standard treatment model for people with HIV (PWH) reporting hazardous alcohol use. DESIGN: Community cluster-randomized trial. METHODS: The Sustainable East Africa Research in Community Health trial (NCT01864603) compared an intervention of annual population HIV testing, universal ART, and patient-centered care with a control of baseline population testing with ART by country standard in 32 Kenyan and Ugandan communities. Adults (15 years or older) completed a baseline Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and were classified as no/nonhazardous (AUDIT-C 0-2 women/0-3 men) or hazardous alcohol use (≥3 women/≥4 men). We compared year 3 ART uptake and viral suppression of PWH reporting hazardous use between intervention and control arms. We compared alcohol use as a predictor of year 3 ART uptake and viral suppression among PWH, by arm. RESULTS: Of 11,070 PWH with AUDIT-C measured, 1723 (16%) reported any alcohol use and 893 (8%) reported hazardous use. Among PWH reporting hazardous use, the intervention arm had higher ART uptake (96%) and suppression (87%) compared with control (74%, adjusted risk ratio [aRR] = 1.28, 95% CI: 1.19 to 1.38; and 72%, aRR = 1.20, 95% CI: 1.10 to 1.31, respectively). Within arm, hazardous alcohol use predicted lower ART uptake in control (aRR = 0.86, 95% CI: 0.78 to 0.96), but not intervention (aRR = 1.02, 95% CI: 1.00 to 1.04); use was not predictive of suppression in either arm. CONCLUSIONS: The Sustainable East Africa Research in Community Health intervention improved ART uptake and viral suppression among PWH reporting hazardous alcohol use and eliminated gaps in ART uptake between PWH with hazardous and no/nonhazardous use. Patient-centered HIV care may decrease barriers to HIV care for PWH with hazardous alcohol use.

Mobility and HIV care engagement: a research agenda.

INTRODUCTION: Mobility is common and an essential livelihood strategy in sub-Saharan Africa (SSA). Mobile people suffer worse outcomes at every stage of the HIV care cascade compared to non-mobile populations. Definitions of mobility vary widely, and research on the role of temporary mobility (as opposed to permanent migration) in HIV treatment outcomes is often lacking. In this article, we review the current landscape of mobility and HIV care research to identify what is already known, gaps in the literature, and recommendations for future research. DISCUSSION: Mobility in SSA is closely linked to income generation, though caregiving, climate change and violence also contribute to the need to move. Mobility is likely to increase in the coming decades, both due to permanent migration and increased temporary mobility, which is likely much more common. We outline three central questions regarding mobility and HIV treatment outcomes in SSA. First, it is unclear what aspects of mobility matter most for HIV care outcomes and if high-risk mobility can be identified or predicted, which is necessary to facilitate targeted interventions for mobile populations. Second, it is unclear what groups are most vulnerable to mobility-associated treatment interruption and other adverse outcomes. And third, it is unclear what interventions can improve HIV treatment outcomes for mobile populations. CONCLUSIONS: Mobility is essential for people living with HIV in SSA. HIV treatment programmes and broader health systems must understand and adapt to human mobility, both to promote the rights and welfare of mobile people and to end the HIV pandemic.

Weight Change Following Switch to Dolutegravir for HIV Treatment in Rural Kenya During Country Roll-Out.

INTRODUCTION: Switch to dolutegravir (DTG) in treatment-experienced people living with HIV (PLH) is associated with excess weight gain in some settings; data are limited from rural low-income settings with low obesity prevalence. METHODS: In rural Kenya, we conducted a retrospective cohort study at 8 HIV clinics and a single-site prospective cohort study including adults switching to DTG during countrywide transition to DTG/tenofovir DF(TDF)/emtricitabine as first-line HIV treatment. In the retrospective analysis, we used preswitch data to model postswitch weight trajectory had each participant not switched to DTG and contrasted observed vs. predicted postswitch weight. In the prospective analysis, we measured weight post-DTG switch and evaluated predictors of 6-month weight change. RESULTS: Our retrospective cohort included 4445 PLH who switched to DTG between 2018 and 2020. Mean 12-month weight change was 0.6 kg preswitch and 0.8 kg postswitch. Among those on TDF throughout (n = 3374; 83% on efavirenz preswitch), 12-month postswitch weight was 0.7 kg more than predicted for women (95% CI: 0.4, 1.0) and similar among men (0.04 kg; 95% CI -0.3, 0.4). In our prospective cohort (n = 135, 100% female), mean 6-month weight change was +0.4 kg (IQR -1.1, 2.0 kg). Predicted gain varied by baseline food insecurity: +1.1 kg (95% CI: 0.34, 1.87) among food secure, -0.09 kg (95% CI -0.71, 0.54) among moderate insecure, and +0.27 kg (95% CI -0.82, 1.36) among severe insecurity. CONCLUSION: In contrast to some reports of large weight gain following switch to DTG, we observed small weight increases in women and no weight change in men following DTG switch when on TDF throughout. Weight gain may be attenuated by food insecurity, though was modest even among food secure.

Two-Stage TMLE to reduce bias and improve efficiency in cluster randomized trials.

Cluster randomized trials (CRTs) randomly assign an intervention to groups of individuals (e.g., clinics or communities) and measure outcomes on individuals in those groups. While offering many advantages, this experimental design introduces challenges that are only partially addressed by existing analytic approaches. First, outcomes are often missing for some individuals within clusters. Failing to appropriately adjust for differential outcome measurement can result in biased estimates and inference. Second, CRTs often randomize limited numbers of clusters, resulting in chance imbalances on baseline outcome predictors between arms. Failing to adaptively adjust for these imbalances and other predictive covariates can result in efficiency losses. To address these methodological gaps, we propose and evaluate a novel two-stage targeted minimum loss-based estimator to adjust for baseline covariates in a manner that optimizes precision, after controlling for baseline and postbaseline causes of missing outcomes. Finite sample simulations illustrate that our approach can nearly eliminate bias due to differential outcome measurement, while existing CRT estimators yield misleading results and inferences. Application to real data from the SEARCH community randomized trial demonstrates the gains in efficiency afforded through adaptive adjustment for baseline covariates, after controlling for missingness on individual-level outcomes.

Two or more significant life-events in 6-months are associated with lower rates of HIV treatment and virologic suppression among youth with HIV in Uganda and Kenya.

Youth living with HIV in sub-Saharan Africa have poor HIV care outcomes. We determined the association of recent significant life-events with HIV antiretroviral treatment (ART) initiation and HIV viral suppression in youth aged 15-24 years living with HIV in rural Kenya and Uganda. This was a cross-sectional analysis of 995 youth enrolled in the SEARCH Youth study. At baseline, providers assessed recent (within 6 months) life-events, defined as changes in schooling/employment, residence, partnerships, sickness, incarceration status, family strife or death, and birth/pregnancy, self-reported alcohol use, being a parent, and HIV-status disclosure. We examined the frequencies of events and their association with ART status and HIV viral suppression (<400 copies/ul). Recent significant life-events were prevalent (57.7%). Having >2 significant life-events (aOR = 0.61, 95% CI:0.45-0.85) and consuming alcohol (aOR = 0.61, 95% CI:0.43-0.87) were associated with a lower odds of HIV viral suppression, while disclosure of HIV-status to partner (aOR = 2.39, 95% CI:1.6-3.5) or to family (aOR = 1.86, 95% CI:1.3-2.7), being a parent (aOR = 1.8, 95% CI:1.2-2.5), and being single (aOR = 1.6, 95% CI:1.3-2.1) had a higher odds. This suggest that two or more recent life-events and alcohol use are key barriers to ART initiation and achievement of viral suppression among youth living with HIV in rural East Africa.Trial registration: ClinicalTrials.gov identifier: NCT03848728..

Effect of a one-time financial incentive on linkage to chronic hypertension care in Kenya and Uganda: A randomized controlled trial.

BACKGROUND: Fewer than 10% of people with hypertension in sub-Saharan Africa are diagnosed, linked to care, and achieve hypertension control. We hypothesized that a one-time financial incentive and phone call reminder for missed appointments would increase linkage to hypertension care following community-based screening in rural Uganda and Kenya. METHODS: In a randomized controlled trial, we conducted community-based hypertension screening and enrolled adults ≥25 years with blood pressure ≥140/90 mmHg on three measures; we excluded participants with known hypertension or hypertensive emergency. The intervention was transportation reimbursement upon linkage (~$5 USD) and up to three reminder phone calls for those not linking within seven days. Control participants received a clinic referral only. Outcomes were linkage to hypertension care within 30 days (primary) and hypertension control <140/90 mmHg measured in all participants at 90 days (secondary). We used targeted minimum loss-based estimation to compute adjusted risk ratios (aRR). RESULTS: We screened 1,998 participants, identifying 370 (18.5%) with uncontrolled hypertension and enrolling 199 (100 control, 99 intervention). Reasons for non-enrollment included prior hypertension diagnosis (n = 108) and hypertensive emergency (n = 32). Participants were 60% female, median age 56 (range 27-99); 10% were HIV-positive and 42% had baseline blood pressure ≥160/100 mmHg. Linkage to care within 30 days was 96% in intervention and 66% in control (aRR 1.45, 95%CI 1.25-1.68). Hypertension control at 90 days was 51% intervention and 41% control (aRR 1.22, 95%CI 0.92-1.66). CONCLUSION: A one-time financial incentive and reminder call for missed visits resulted in a 30% absolute increase in linkage to hypertension care following community-based screening. Financial incentives can improve the critical step of linkage to care for people newly diagnosed with hypertension in the community.

Providers' Attitudes and Experiences with Pre-Exposure Prophylaxis Implementation in a Population-Based Study in Kenya and Uganda.

Pre-exposure prophylaxis (PrEP) implementation is underway across sub-Saharan Africa. However, little is known about health care providers' experiences with PrEP provision in generalized epidemic settings, particularly outside of selected risk groups. In this study (NCT01864603), universal access to PrEP was offered to adolescents and adults at elevated risk during population-level HIV testing in rural Kenya and Uganda. Providers received training on PrEP prescribing and support from local senior clinicians. We conducted in-depth interviews with providers (n = 19) in four communities in Kenya and Uganda to explore the attitudes and experiences with implementation. Transcripts were coded and analyzed using interpretivist methods. Providers had heterogenous attitudes toward PrEP in its early implementation: some expressed enthusiasm, while others feared being blamed for "failures" (HIV seroconversions) if participants were nonadherent, or that offering PrEP would increase "immorality." Providers supported PrEP usage among HIV-serodifferent couples, whose mutual support for daily pill-taking facilitated harmony and protection from HIV. Providers reported challenges with counseling on "seasons of risk," and safely stopping and restarting PrEP. They felt uptake was hampered for women by difficulties negotiating with partners, and for youth by parental consent requirements. They believed PrEP continuation was hindered by transportation costs, stigma, pill burden, and side effects, and was facilitated by counseling, proactive management of side effects, and home/community-based provision. Providers are critical "implementation actors" in interventions to promote adoption of new technologies such as PrEP. Dedicated training and ongoing support for providers may facilitate successful scale-up.