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.

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.

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.

Blurring cluster randomized trials and observational studies: Two-Stage TMLE for subsampling, missingness, and few independent units.

Cluster randomized trials (CRTs) often enroll large numbers of participants; yet due to resource constraints, only a subset of participants may be selected for outcome assessment, and those sampled may not be representative of all cluster members. Missing data also present a challenge: if sampled individuals with measured outcomes are dissimilar from those with missing outcomes, unadjusted estimates of arm-specific endpoints and the intervention effect may be biased. Further, CRTs often enroll and randomize few clusters, limiting statistical power and raising concerns about finite sample performance. Motivated by SEARCH-TB, a CRT aimed at reducing incident tuberculosis infection, we demonstrate interlocking methods to handle these challenges. First, we extend Two-Stage targeted minimum loss-based estimation to account for three sources of missingness: (i) subsampling; (ii) measurement of baseline status among those sampled; and (iii) measurement of final status among those in the incidence cohort (persons known to be at risk at baseline). Second, we critically evaluate the assumptions under which subunits of the cluster can be considered the conditionally independent unit, improving precision and statistical power but also causing the CRT to behave like an observational study. Our application to SEARCH-TB highlights the real-world impact of different assumptions on measurement and dependence; estimates relying on unrealistic assumptions suggested the intervention increased the incidence of TB infection by 18% (risk ratio [RR]=1.18, 95% confidence interval [CI]: 0.85-1.63), while estimates accounting for the sampling scheme, missingness, and within community dependence found the intervention decreased the incident TB by 27% (RR=0.73, 95% CI: 0.57-0.92).

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.

Sex specific differences in HIV status disclosure and care engagement among people living with HIV in rural communities in Kenya and Uganda.

Non-disclosure of human immunodeficiency virus (HIV) status can hinder optimal health outcomes for people living with HIV (PLHIV). We sought to explore experiences with and correlates of disclosure among PLHIV participating in a study of population mobility. Survey data were collected from 1081 PLHIV from 2015-16 in 12 communities in Kenya and Uganda participating in a test-and-treat trial (SEARCH, NCT#01864603). Pooled and sex-stratified multiple logistic regression models examined associations of disclosure with risk behaviors controlling for covariates and community clustering. At baseline, 91.0% (n = 984) of PLHIV had disclosed their serostatus. Amongst those who had never disclosed, 31% feared abandonment (47.4% men vs. 15.0% women; p = 0.005). Non-disclosure was associated with no condom use in the past 6 months (aOR = 2.44; 95%CI, 1.40-4.25) and with lower odds of receiving care (aOR = 0.8; 95%CI, 0.04-0.17). Unmarried versus married men had higher odds of non- disclosure (aOR = 4.65, 95%CI, 1.32-16.35) and no condom use in the past 6 months (aOR = 4.80, 95%CI, 1.74-13.20), as well as lower odds of receiving HIV care (aOR = 0.15; 95%CI, 0.04-50 0.49). Unmarried versus married women had higher odds of non-disclosure (aOR = 3.14, 95%CI, 1.47-6.73) and lower odds of receiving HIV care if they had never disclosed (aOR = 0.05, 95%CI, 0.02-0.14). Findings highlight gender differences in barriers to HIV disclosure, use of condoms, and engagement in HIV care. Interventions focused on differing disclosure support needs for women and men are needed and may help facilitate better care engagement for men and women and improve condom use in men.

Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections.

BACKGROUND: Interventions to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM) are needed. METHODS: We conducted an open-label, randomized study involving MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and who had had Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter. RESULTS: Of 501 participants (327 in the PrEP cohort and 174 in the PLWH cohort), 67% were White, 7% Black, 11% Asian or Pacific Islander, and 30% Hispanic or Latino. In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of -21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P<0.001). In the PLWH cohort, an STI was diagnosed in 36 of 305 quarterly visits (11.8%) in the doxycycline group and 39 of 128 quarterly visits (30.5%) in the standard-care group, for an absolute difference of -18.7 percentage points and a relative risk of 0.38 (95% CI, 0.24 to 0.60; P<0.001). The incidences of the three evaluated STIs were lower with doxycycline than with standard care; in the PrEP cohort, the relative risks were 0.45 (95% CI, 0.32 to 0.65) for gonorrhea, 0.12 (95% CI, 0.05 to 0.25) for chlamydia, and 0.13 (95% CI, 0.03 to 0.59) for syphilis, and in the PLWH cohort, the relative risks were 0.43 (95% CI, 0.26 to 0.71), 0.26 (95% CI, 0.12 to 0.57), and 0.23 (95% CI, 0.04 to 1.29), respectively. Five grade 3 adverse events and no serious adverse events were attributed to doxycycline. Of the participants with gonorrhea culture available, tetracycline-resistant gonorrhea occurred in 5 of 13 in the doxycycline groups and 2 of 16 in the standard-care groups. CONCLUSIONS: The combined incidence of gonorrhea, chlamydia, and syphilis was lower by two thirds with doxycycline postexposure prophylaxis than with standard care, a finding that supports its use among MSM with recent bacterial STIs. (Funded by the National Institutes of Health; DoxyPEP ClinicalTrials.gov number, NCT03980223.).

Impact of COVID-19 Response on the HIV Epidemic in Men Who Have Sex With Men in San Francisco County: The Importance of Rapid Return to Normalcy.

BACKGROUND: In response to the COVID-19 pandemic, San Francisco County (SFC) had to shift many nonemergency health care resources to COVID-19, reducing HIV control resources. We sought to quantify COVID-19 effects on HIV burden among men who have sex with men (MSM) as SFC returns to pre-COVID service levels and progresses toward the Ending the HIV Epidemic (EHE) goals. SETTING: Microsimulation model of MSM in SFC tracking HIV progression and treatment. METHODS: Scenario analysis where services affected by COVID-19 [testing, care engagement, pre-exposure prophylaxis (PrEP) uptake, and retention] return to pre-COVID levels by the end of 2022 or 2025, compared against a counterfactual where COVID-19 changes never occurred. We also examined scenarios where resources are prioritized to reach new patients or retain of existing patients from 2023 to 2025 before all services return to pre-COVID levels. RESULTS: The annual number of MSM prescribed PrEP, newly acquired HIV, newly diagnosed, and achieving viral load suppression (VLS) rebound quickly after HIV care returns to pre-COVID levels. However, COVID-19 service disruptions result in measurable reductions in cumulative PrEP use, VLS person-years, incidence, and an increase in deaths over the 2020-2035 period. The burden is statistically significantly larger if these effects end in 2025 instead of 2022. Prioritizing HIV care/prevention initiation over retention results in more person-years of PrEP but less VLS person-years and more deaths, influencing EHE PrEP outcomes. CONCLUSIONS: Earlier HIV care return to pre-COVID levels results in lower cumulative HIV burdens. Resource prioritization decisions may differentially affect different EHE goals.

Nothing about us without us: Community-based participatory research to improve HIV care for mobile patients in Kenya and Uganda.

BACKGROUND: Population mobility is prevalent and complex in sub-Saharan Africa, and can disrupt HIV care and fuel onward transmission. While differentiated care models show promise for meeting the needs of mobile populations by addressing care cascade gaps, the voices of mobile populations need to be included when designing care delivery models. We assessed the unmet needs of mobile populations and engaged mobile stakeholders in the design and implementation of service delivery to improve care outcomes for mobile people living with HIV (PLHIV). METHODS: CBPR was conducted in 12 rural communities in Kenya and Uganda participating in a mobility study within the Sustainable East Africa Research in Community Health (SEARCH) test-and-treat trial (NCT# 01864603) from 2016 to 2019. Annual gender-balanced meetings with between 17 and 33 mobile community stakeholders per meeting were conducted in local languages to gather information on mobility and its influence on HIV-related outcomes. Discussions were audio-recorded, transcribed and translated into English. Findings were shared at subsequent meetings to engage mobile stakeholders in interpretation. At year three, intervention ideas to address mobile populations' needs were elicited. After refinement, these intervention options were presented to the same communities for prioritization the following year, using a participatory ranking approach. RESULTS: Transit hubs, trading centers, and beach sites were identified as desirable service locations. Communities prioritized mobile health 'cards' with electronic medical records and peer-delivered home-based services. Mobile health clinics, longer antiretroviral refills, and 24/7 (after service) were less desirable options. Care challenges included: lack of transfer letters to other clinics; inability to adhere to scheduled appointments, medication regimens, and monitoring of treatment outcomes while mobile amongst others. CONCLUSIONS: Iterative discussions with mobile community stakeholders elicited communities' health priorities and identified challenges to achieving HIV care cascade outcomes. Understanding the mobility patterns and unique needs of mobile populations through responsive community engagement is critical.

Condom, modern contraceptive, and dual method use are associated with HIV status and relationship concurrency in a context of high mobility: A cross-sectional study of women of reproductive age in rural Kenya and Uganda, 2016.

OBJECTIVES: Mobility (international/internal migration, and localized mobility) is a key driver of the HIV epidemic. While mobility is associated with higher-risk sexual behavior in women, a possible association with condom, modern contraceptive, and dual method use among women living with HIV (WLHIV), is unknown. In addition, HIV status and sexual behaviors such as relationship concurrency may also affect condom, modern contraceptive, and dual method use. STUDY DESIGN: We surveyed sexually active women (N = 1067) aged 15 to 49 in 12 communities in Kenya and Uganda participating in a test-and-treat trial in 2015 to 2016. Generalized (unordered) multinomial logistic regression models accounting for community clustering examined associations between mobility (overnight travel away from home in past 6 months and any migration within past 2 years) and condom, modern contraceptive (i.e., oral contraceptive pills, injectables, intrauterine devices, implants, vasectomy, tubal ligation; excluding male/female condoms), and dual method use within past 6 months, adjusting for key covariates such as HIV status and relationship concurrency. RESULTS: WLHIV relative to HIV-negative women (ratios of relative risk [RRR] = 3.76, 95% confidence interval [CI]: 2.40-5.89), and women in concurrent relative to monogamous relationships (RRR = 4.03, 95% CI 1.9-8.50) had higher odds of condom use alone. In contraceptive use models, WLHIV relative to HIV-negative women were less likely to use modern contraceptive methods alone (RRR = 0.51, 95% CI 0.36-0.73). Relationship concurrency (RRR = 4.51, 95% CI 2.10-9.67) and HIV status (RRR = 3.97, 95% CI 2.43-6.50) were associated with higher odds of dual method use while mobility was marginally associated with higher odds of dual method use (RRR = 1.65, 95% CI 0.99-2.77, p = 0.057). CONCLUSIONS: Mobility had a potential impact on dual method use in Kenya and Uganda. In addition, our findings highlight that WLHIV were using condoms and dual methods more, but modern contraceptives less, than HIV-negative women. Those in concurrent relationships were also more likely to use condoms or dual methods. These findings suggest that in a context of high mobility, women may be appropriately assessing risks and taking measures to protect themselves and their partners from unintended pregnancies and acquisition and transmission of HIV. IMPLICATIONS: Our findings point to a need to strengthen accessibility of sexual and reproductive health services for both mobile and residentially stable women in settings of high mobility and high HIV prevalence.

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..

Drought, HIV Testing, and HIV Transmission Risk Behaviors: A Population-Based Study in 10 High HIV Prevalence Countries in Sub-Saharan Africa.

Droughts are associated with poor health outcomes and disruption of public health programming. Data on the association between drought and HIV testing and transmission risk behaviors are limited. We combined data from Demographic and Health Surveys from 10 high HIV prevalence sub-Saharan African countries with a high-resolution measure of drought. We estimated the association between drought and recent HIV testing, report of condomless sex, and number of sexual partners in the last year. Respondents exposed to drought were less likely to have an HIV test and more likely to have condomless sex, although effect sizes were small. We found evidence for effect modification by sex and age for the association between drought and HIV testing, such that the negative association between drought and HIV testing was strongest among men (marginal risk ratio [mRR] 0.92, 95% CI 0.89-0.95) and adolescents (mRR 0.90, 95% CI 0.86-0.93). Drought may hinder HIV testing programs in countries with high HIV prevalence.

The Association Between Social Network Characteristics and Tuberculosis Infection Among Adults in 9 Rural Ugandan Communities.

BACKGROUND: Social network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies. METHODS: We assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation. RESULTS: Among 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]). CONCLUSIONS: Social networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.

Mobility is Associated with Higher-risk Sexual Partnerships Among Both Men and Women in Co-resident Couples in Rural Kenya and Uganda: A Longitudinal Cohort Study.

Population mobility is associated with higher-risk sexual behaviors in sub-Saharan Africa and is a key driver of the HIV epidemic. We conducted a longitudinal cohort study to estimate associations between recent mobility (overnight travel away from home in past six months) or migration (changes of residence over defined geopolitical boundaries) and higher-risk sexual behavior among co-resident couples (240 couples aged ≥ 16) from 12 rural communities in Kenya and Uganda. Data on concurrent mobility and sexual risk behaviors were collected every 6-months between 2015 and 2020. We used sex-pooled and sex-stratified multilevel models to estimate associations between couple mobility configurations (neither partner mobile, male mobile/female not mobile, female mobile/male not mobile, both mobile) and the odds of higher-risk (casual, commercial sex worker/client, one night stand, inherited partner, stranger) and concurrent sexual partnerships based on who was mobile. On average across all time points and subjects, mobile women were more likely than non-mobile women to have a higher-risk partner; similarly, mobile men were more likely than non-mobile men to report a higher-risk partnership. Men with work-related mobility versus not had higher odds of higher-risk partnerships. Women with work-related mobility versus not had higher odds of higher-risk partnerships. Couples where both members were mobile versus neither had greater odds of higher-risk partnerships. In analyses using 6-month lagged versions of key predictors, migration events of men, but not women, preceded higher-risk partnerships. Findings demonstrate HIV risks for men and women associated with mobility and the need for prevention approaches attentive to the risk-enhancing contexts of mobility.

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.

Analysis of Heavy Rainfall in Sub-Saharan Africa and HIV Transmission Risk, HIV Prevalence, and Sexually Transmitted Infections, 2005-2017.

Importance: Extreme precipitation, including heavy rains and flooding, is associated with poor health outcomes mediated in part by decreases in income and food production. However, the association between heavy rains and HIV burden is unknown. Objective: To investigate the association between heavy rainfall, HIV prevalence, and HIV transmission risk over a 12-year span in sub-Saharan Africa. Design, Setting, and Participants: A cross-sectional population-based study, using data collected from the 2005-2017 Demographic and Health Surveys, was conducted in 21 countries in sub-Saharan Africa and analyzed from July 29, 2021, to June 14, 2022. Exposures: Heavy rainfall was defined based on the extent to which annual rainfall deviated from the historical average (standardized precipitation index ≥1.5) at the enumeration area level. Main Outcomes and Measures: HIV, self-reported sexually transmitted infections (STIs), and number of sexual partners. Results: The study included 288 333 participants aged 15 to 59 years; 172 344 were women (59.8%), and 183 378 were married (63.6%). Mean (SD) age was 31.9 (10.0) years. Overall, 42.4% of participants were exposed to at least 1 year of heavy rainfall in the past 10 years. Each year of heavy rainfall was associated with 1.14 (95% CI, 1.11-1.18) times the odds of HIV infection and 1.11 (95% CI, 1.07-1.15) times the odds of an STI in the past 12 months. There was also an association between heavy rainfall and the reported number of sexual partners (incident rate ratio, 1.12; 95% CI, 1.10-1.15). The odds were greater for the association between heavy rainfall and HIV prevalence and STIs among participants aged older than 20 years and participants in rural areas. Conclusions and Relevance: The findings of this study suggest that heavy rainfall was associated with a higher HIV burden in sub-Saharan Africa. The association between heavy rainfall and STIs and number of sexual partners suggests that an increase in the risk of sexual transmission is a plausible mechanism for the observed findings around HIV prevalence. Heavy rainfall could also worsen food insecurity, increasing the risk of transactional sex, or cause damage to public health infrastructure, reducing access to STI education, HIV testing, and treatment.

Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa.

The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 gag and 488 pol HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections. Putative transmission clusters, with a 1.5% pairwise genetic distance threshold, were inferred from maximum likelihood phylogenies; clusters arising after the start of SEARCH were identified with Bayesian time-calibrated phylogenies. Our phylodynamic approach identified nine clusters arising after the SEARCH start date: eight pairs and one triplet, representing mostly opposite-gender linked (6/9), within-community transmissions (7/9). Two clusters contained individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, both linked to intervention communities. The identification of SEARCH-incident, within-community transmissions reveals the role of unsuppressed individuals in sustaining the epidemic in both arms of a UTT trial setting. The presence of transmitted NNRTI resistance, implying treatment failure to the efavirenz-based antiretroviral therapy (ART) used during SEARCH, highlights the need to improve delivery and adherence to up-to-date ART recommendations, to halt HIV-1 transmission.

"I was still very young": agency, stigma and HIV care strategies at school, baseline results of a qualitative study among youth in rural Kenya and Uganda.

INTRODUCTION: Adolescents and young adults living with HIV (AYAH) have the lowest rates of retention in HIV care and antiretroviral therapy (ART) adherence, partly due to the demands of school associated with this life stage, to HIV-related stigma and to fears of serostatus disclosure. We explore the implications of school-based stigma and disclosure on the development of agency during a critical life stage in rural Kenya and Uganda. METHODS: We conducted a qualitative study in the baseline year of the SEARCH Youth study, a combination intervention using a life-stage approach among youth (15-24 years old) living with HIV in western Kenya and southwestern Uganda to improve viral load suppression and health outcomes. We conducted in-depth, semi-structured interviews in 2019 with three cohorts of purposively selected study participants (youth [n = 83], balanced for sex, life stage and HIV care status; recommended family members of youth [n = 33]; and providers [n = 20]). Inductive analysis exploring contextual factors affecting HIV care engagement revealed the high salience of schooling environments. RESULTS: Stigma within school settings, elicited by non-consensual serostatus disclosure, medication schedules and clinic appointments, exerts a constraining factor around which AYAH must navigate to identify and pursue opportunities available to them as young people. HIV status can affect cross-generational support and cohort formation, as AYAH differ from non-AYAH peers because of care-related demands affecting schooling, exams and graduation. However, adolescents demonstrate a capacity to overcome anticipated stigma and protect themselves by selectively disclosing HIV status to trusted peers and caregivers, as they develop a sense of agency concomitant with this life stage. Older adolescents showed greater ability to seek out supportive relationships than younger ones who relied on adult caregivers to facilitate this support. CONCLUSIONS: School is a potential site of HIV stigma and also a setting for learning how to resist such stigma. School-going adolescents should be supported to identify helpful peers and selectively disclose serostatus as they master decision making about when and where to take medications, and who should know. Stigma is avoided by fewer visits to the clinic; providers should consider longer refills, discreet packaging and long-acting, injectable ART for students.

Testing a social network approach to promote HIV self-testing and linkage to care among fishermen at Lake Victoria: study protocol for the Owete cluster randomized controlled trial.

BACKGROUND: Nearly 50% of men living with HIV in many countries are unaware of their HIV status; men also have lower uptake of HIV treatment and pre-exposure prophylaxis (PrEP). In SSA, highly mobile men such as those working in fishing communities alongside Lake Victoria have low uptake of HIV testing and low rates of linkage to HIV treatment and PrEP, despite increasing availability of these services. HIV self-testing (HIVST) kits hold promise for overcoming barriers to HIV testing and linkage to services for HIV-positive and HIV-negative men. We describe here a protocol for an HIV status-neutral, social network-based approach to promote HIV testing, linkage to care and prevention, and better health outcomes, including adherence, in fishermen around Lake Victoria. METHODS: Utilizing beach management unit (BMU) registries of fishermen operating in three Lake Victoria fishing communities in Siaya County, Kenya, we completed a census and social network mapping to identify close social networks of men. Network clusters identified by a socially-central lead ("promotor") and selected to ensure maximal separation between treatment and control will be randomized. Promotors in both arms will receive basic HIV training; intervention promotors are further trained in HIVST to distribute kits to their cluster, while control promotors will distribute to their cluster vouchers for free HIVST at nearby clinics. We will test whether these promoters can enhance linkage to ART and PrEP after self-testing, thereby addressing a key limitation of HIVST. We will also measure 6- and 12-month viral load in those living with HIV and PrEP adherence among those without HIV via urine tenofovir levels as objective markers of adherence. DISCUSSION: This study has the potential to improve HIV health and promote HIV prevention among a hard to reach, at-risk, and highly mobile population of men in Western Kenya-a critical population in Kenya's HIV prevention and treatment program. Further, if successful, this innovative social networks-based model could be scaled at the regional level to address HIV prevention and care among similarly at-risk populations of men in eastern Africa and inland fisheries settings across the continent. TRIAL REGISTRATION: Self-Test Strategies and Linkage Incentives to Improve ART and PrEP Uptake in Men, registered on February 26, 2021, registration # NCT04772469 .