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Rationale: Although interferon (IFN)-gamma release assays are approved for the diagnosis of latent tuberculosis infection (LTBI), limited data exist regarding their performance in HIV infection.Objectives: To compare tuberculin skin test (TST) results to the commercial IFN-gamma release assay QuantiFERON-TB Gold In-Tube (QFT) for the diagnosis of LTBI in HIV-infected adults.Methods: A total of 294 HIV-infected subjects sampled from two San Francisco cohorts underwent TST, using 5 TU of purified protein derivative, and QFT, measuring IFN-gamma response to Mycobacterium tuberculosis-specific RD-1 antigens.Main Results: Of 294 participants, 205 (70%) returned for an evaluable TST. Concordance between QFT and TST was 89.3% (kappa=0.37, p=0.007). However, in subjects with positive test results by either TST or QFT, only 28% (8/29) had positive test results by both modalities. TST-positive/QFT-negative discordant results were found in 5.1% of subjects and TST-negative/QFT-positive discordance in 5.6%. Indeterminate QFT results occurred in 5.1%, all due to a failure to respond to the phytohemagglutinin-positive control. Subjects with a CD4(+) count of less than 100 cells/mm(3) had a relative risk of an indeterminate result of 4.24 (95% confidence interval, 1.55-11.61; p=0.003) compared with those with a CD4(+) count of 100 or more.Conclusions: Overall concordance between QFT and TST in HIV infection was high, but agreement among subjects with positive tests by either modality was low. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) plays a key role in the epidemiology and pathogenesis of disease. The purpose of this study was to determine the characteristics and dynamics of nasal strains of MRSA, as well as their relation to community-associated disease activity. METHODS: This study is a cross-sectional survey and molecular epidemiologic analysis of nasal colonization by S. aureus in homeless and runaway youths, an underserved population at high risk for staphylococcal disease. RESULTS: Of the 308 study participants, 27.6% carried S. aureus, and 6.2% carried MRSA. Subgroups of individuals with increased MRSA carriage rates were also at highest risk for community-associated MRSA infection; these subgroups included individuals with either HIV infection or AIDS, injection drug users, patients with abscesses, and those recently hospitalized. Multilocus sequence typing and pulsed-field gel electrophoresis identified 2 genotypes--ST59:P (USA1000) and ST8:S (USA300)--that accounted for 84.2% (16/19) of the MRSA isolates carried. The genotypes were distinct from nosocomial genotypes endemic in the hospital, although they originated from individuals with prior exposure to health care. CONCLUSIONS: Comparison of MRSA strains from asymptomatic carriers versus concurrently collected community-associated clinical strains from patients treated at local health-care facilities allowed for the identification of 3 population dynamics of nasal strains of MRSA: (1) endemic clones--for example, ST8:C and ST59:P--sustained asymptomatic carriage and infection over prolonged periods; (2) an epidemic clone, ST8:S, demonstrated enhanced capacity for rapid transmission and widespread infections; and (3) an outbreak clone, ST30:Z (USA1100), was highly infectious but exhibited poor asymptomatic transmission. Copyright © 2005 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Much of the literature on pulmonary embolism that is commonly referenced by emergency physicians begins with statistics concerning how often the diagnosis is missed and the lethality of pulmonary embolism if undiagnosed and untreated. It is likely that many emergency physicians continue to pursue an aggressive diagnostic strategy even in low-risk patients because of concerns about the potential for poor patient outcome and the medicolegal consequences of a missed diagnosis. The believed and often-quoted mortality and recurrence rates for untreated or missed pulmonary embolism are 26% to 30%. However, these figures originate from investigations that have little relevance to modern emergency medicine, which include studies dating to the 1940s, many of which have significant methodologic pitfalls. These data are also based primarily on either inpatient or autopsy populations, neither of which is representative of patients treated in the emergency department (ED). Analysis of untreated or missed pulmonary embolism in ambulatory patients reveals mortality and recurrence rates of less than 5%. This article discusses the background of commonly quoted pulmonary embolism statistics and highlights the need for future investigations enrolling ED patients that focus on disease outcome in this population. [ABSTRACT FROM AUTHOR]

We compared electronic medication monitoring and electronic monitoring adjusted by interview with an unannounced pill-count adherence measure, in a cross-sectional analysis (n = 42). We used the following measures (a) electronic monitored doses (EMD: # medication monitor openings/# doses prescribed), (b) adjusted electronically monitored doses (AEMD: EMD adjusted by the number of extra openings and extra doses removed), (c) percentage of days dose taken (PDDT: % days the medication monitor was opened at least once, and (d) unannounced pill count (PC). The results showed that AEMD, EMD, and PDDT were significantly associated with PC adherence. AEMD explained 83% of the variation in PC adherence, EMD 49%, and PDDT 58%. EMD adherence was significantly lower than PC adherence (p = .02). Electronic medication monitoring measures were closely related to PC adherence. AEMD was more closely associated than EMD or PDDT. EMD may underestimate adherence due to the removal of multiple doses from the bottle at one time. [ABSTRACT FROM AUTHOR]

Persons infected with human immunodeficiency virus (HIV) have cellular cytotoxicity defects. Interleukin (IL)-12 is a potent stimulator of cytotoxicity. Fifteen HIV-infected patients were studied in a phase 1, single-dose escalation trial of human recombinant IL-12. One day after subjects received an IL-12 dose of 300 or 1000 ng/kg, they had a reduction in absolute lymphocyte count and peripheral blood mononuclear cell recovery. In evaluable patients 24 h after IL-12 administration, there was a 31% reduction overall in NK cell cytotoxicity (NKC) to HIV-infected cells at all doses and a 52% reduction in antibody-dependent cellular cytotoxicity (ADCC) at doses of 300 and 1000 ng/kg. In vitro incubation of patients' cells with IL-12 (before IL-12 administration) for 24 h increased NKC but had no effect on ADCC. The paradoxic acute reduction in cell number and cytotoxicity in vivo may be due to NK cell trafficking or regulatory cytokine mechanisms not apparent in vitro. [ABSTRACT FROM AUTHOR]

Abstract Background Daily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance-conferring Plasmodium falciparum mutations in HIV-infected children receiving daily TS and HIV-uninfected children not taking TS. Materials and methods Subjects were 292 HIV-infected and 517 uninfected children from two cohort studies in Kampala, Uganda observed from August 2006 to December 2008. Daily TS was given to HIV-infected, but not HIV-uninfected children and all participants were provided an insecticide-treated bed net. Standardized protocols were used to measure the incidence of malaria and identify markers of antifolate resistance. Results Sixty-five episodes of falciparum malaria occurred in HIV-infected and 491 episodes in uninfected children during the observation period. TS was associated with a protective efficacy of 80% (0.10 vs. 0.45 episodes per person year, p < 0.001), and efficacy did not vary over three consecutive 9.5 month periods (81%, 74%, 80% respectively, p = 0.506). The prevalences of dhfr 51I, 108N, and 59R and dhps 437G and 540E mutations were each over 90% among parasites infecting both HIV-infected and uninfected children. Prevalence of the dhfr 164L mutation, which is associated with high-level resistance, was significantly higher in parasites from HIV-infected compared to uninfected children (8% vs. 1%, p = 0.001). Sequencing of the dhfr and dhps genes identified only one additional polymorphism, dhps 581G, in 2 of 30 samples from HIV-infected and 0 of 54 samples from uninfected children. Conclusion Despite high prevalence of known anti-folate resistance-mediating mutations, TS prophylaxis was highly effective against malaria, but was associated with presence of dhfr 164L mutation.

Background: Much of the latent tuberculosis (TB) reservoir is established in childhood and adolescence. Yet, age-specific data on prevalence and predictors of infection in this population are sparse and needed to guide prevention and case finding., Methods: From December 2021 to June 2023, we measured TB infection in children 1-17 years in 25 villages in rural Southwestern Uganda. We defined TB infection as a positive QuantiFERON Gold Plus Test (QFT). We estimated overall and age-stratified population-level prevalence and adjusted risk ratios (aRR) of TB infection for individual, household, and community-based predictors, accounting for age, TB contact, and clustering by household., Results: Estimated TB infection prevalence was 9.6% [95% confidence interval (CI): 8.7-10.5%] among the 5789 participants, and prevalence varied slightly with age. Household-level risk factors included crowding (aRR: 1.25, 95% CI: 1.03-1.53), indoor cooking (aRR: 1.62, 95% CI: 1.14-2.30), living with ≥2 persons who drink alcohol (aRR: 1.47, 95% CI: 1.04-2.07). The predominant community-based risk factor was child mobility (aRR: 1.67, 95% CI: 1.24-2.26). In age-stratified analyses, household predictors were important in early childhood but not adolescence, where mobility was predominant (aRR: 1.66, 95% CI: 1.13-2.44)., Conclusion: We detected a high prevalence of TB infection in children and adolescents in rural Uganda. On a population level, TB risk factors change throughout the early life course, with child mobility a key risk factor in adolescence. Age-specific TB case finding and prevention strategies that address both household and extra-household risk factors are needed to address TB transmission., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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)., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. [br]For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Potential conflicts of interest. G. C. reports participation on a data safety monitoring board or advisory board as a member of a data monitoring committee for an NIH-funded clinical trial (TB Screening Improves Preventive Therapy Uptake [TB SCRIPT] trial). E. D. C. reports consulting fees from the Infectious Diseases Research Collaboration, Kampala, Uganda (paid to the author for Integrated HIV and Hypertension Study consulting). D. V. H. reports nonfinancial support from Gilead (drug donation for an NIH study) and Abbott (diagnostic test donation). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ayieko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022. The Author(s).)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Okorie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.)., (Copyright © 2023 Massachusetts Medical Society.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: Potential conflicts of interest. G. C. reports participation on a data safety monitoring board or advisory board as a member of a data monitoring committee for an National Institutes of Health (NIH)–funded clinical trial (TB Screening Improves Preventive Therapy Uptake [TB SCRIPT] trial). E. D. C. reports support from the NIH (grant 1R01AI151209-01 [paid to institution]) and consulting fees from the Infectious Diseases Research Collaboration, Kampala, Uganda (paid to the author for Integrated HIV & Hypertension Study consulting). D. V. H. reports nonfinancial support from Gilead (drug donation for an NIH study) and Abbott (diagnostic test donation). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2022. Published by Elsevier Ltd.)

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..

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., (Copyright © 2022. Published by Elsevier Inc.)

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.

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.

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.

Objectives: We examined sex-specific associations of partner age disparity and relationship concurrency with Neisseria gonorrhoeae and/or Chlamydia trachomatis (NG/CT) infection, higher-risk relationships, and condom use as proxies for HIV risk., Methods: Data were collected in 2016 from 2179 adults in 12 communities in Uganda and Kenya. Logistic regression models examined associations of age disparity and relationship concurrency with NG/CT infection, condom use, and higher-risk (commercial sex and other higher-risk) relationships in the past 6 months, controlling for covariates., Results: Partner age and relationship concurrency were associated with NG/CT infection in women but not men. Relative to women in age-disparate relationships, women in both age-disparate and age-homogeneous relationships had higher odds of NG/CT infection (adjusted odds ratio [aOR]=3.82, 95% confidence interval [CI]: 1.46-9.98). Among men and women, partnership concurrency was associated with higher-risk partnerships. In addition, relative to those with a single age-homogeneous partner, those with concurrent age-homogeneous partners had higher odds of condom use (men: aOR=2.85, 95% CI: 1.89-4.31; women: aOR=2.99, 95% CI: 1.52-5.89). Concurrent age-disparate partnerships were associated with condom use among men only (aOR=4.02, 95% CI: 2.54-6.37)., Conclusion: Findings underscore the importance of targeted HIV prevention efforts for couples in age-disparate and concurrent relationships., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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 ., (© 2022. The Author(s).)

Objective: We examined whether human mobility was associated with antiretroviral treatment adherence, measured via antiretroviral hair concentrations., Design: This is a cross-sectional analysis of adults on antiretroviral treatment in East Africa at baseline in an observational cohort study., Methods: Participants reported recent mobility (overnight travel) and histories of migration (changes of residence), including reasons, frequency/duration, and locations. Hair antiretroviral concentrations were analyzed using validated methods. We estimated associations between mobility and antiretroviral concentrations via linear regression adjusted for age, sex, region, years on treatment., Results: Among 383 participants, half were women and the median age was 40. Among men, 25% reported recent work-related mobility, 30% nonwork mobility, and 11% migrated in the past year (mostly across district boundaries); among women, 6 and 57% reported work-related and nonwork mobility, respectively, and 8% recently migrated (mostly within district). Those reporting work-related trips 2 nights or less had 72% higher hair antiretroviral levels (P = 0.02) than those who did not travel for work; in contrast, nonwork mobility (any duration, vs. none) was associated with 24% lower levels (P = 0.06). Intra-district migrations were associated with 59% lower antiretroviral levels than nonmigrants (P = 0.003) while inter-district migrations were not (27% higher, P = 0.40)., Conclusion: We found that localized/intra-district migration and nonwork travel-more common among women-were associated with lower adherence, potentially reflecting care interruptions or staying with family/friends unaware of the participants' status. In contrast, short work-related trips-more common among men-were associated with higher adherence, perhaps reflecting higher income. Adherence interventions may require tailoring by sex and forms of mobility., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Universal testing and treatment for HIV has shown promise as an approach to reduce mortality and lower HIV incidence. Evidence on the economic effects of this approach on individuals and households in low-resource settings is scarce. We aimed to examine the effect of universal HIV testing and treatment on a range of economic outcomes., Methods: We collected data in household surveys done over a 3-year period in a sample of HIV-positive and HIV-negative adults participating in a cluster-randomised trial of universal HIV testing and treatment in 32 rural communities in Kenya and Uganda. Communities of approximately 10 000 people were pair-matched on the basis of geographical and population characteristics, with the best-matching 16 pairs randomly assigned (1:1) to intervention or control groups. Participants in intervention communities received annual HIV and multidisease testing, universal antiretroviral therapy (ART) eligibility, and patient-centred care. Participants in control communities received baseline testing and medical care according to national guidelines. We analysed employment and health-care utilisation outcomes for working-age adults (age 18-65 years) and education outcomes for school-age children (6-17 years) using data from 3 years after the intervention. This trial is now complete, and is registered with ClinicalTrials.gov, NCT01864603., Findings: Between July 9, 2013, and June 15, 2017, we collected survey data on 8198 working-age adults and 6755 school-age children. Compared with adults living with HIV in control communities, adults living with HIV in intervention communities were more likely to be employed (difference 9·7% [95% CI 2·1 to 18·3]), less likely to seek health care (-10·3% [-22·0 to 0·1]), and less likely to spend money on health care (-12·7% [-22·4 to 0·6]) 3 years after the intervention. We found no significant differences in outcomes between HIV-negative adults in intervention and control communities. Among children in households with HIV-positive adults, the intervention led to a 7·3% (95% CI 1·0 to 15·1) increase in primary school completion after 3 years in intervention communities compared with control communities., Interpretation: Universal HIV testing and treatment improved employment outcomes and other indicators of socioeconomic wellbeing for HIV-positive adults and children in their households, but had no effect on HIV-negative adults. Our findings suggest that the considerable investments needed to expand ART access might have substantial short-term and long-term economic returns., Funding: National Institutes of Health., Competing Interests: Declaration of interests EDC reports grants from the European and Developing Countries Clinical Trials Partnership. CRC reports grants by the National Institutes of Health and Centers for Disease Control and Prevention, serves as Chair of the Scientific Advisory Board at Osel, and reports receiving fees for legal consultation from and has stock options at Osel and Evvy. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: We tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing., Methods: In the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years. Comparisons between study arms used a cluster-level analysis with survival estimates from Kaplan-Meier; estimates of ART start among ART-naive persons treated death as a competing risk., Results: Among 13 266 adults with HIV, 2973 (22.4%) had CD4 ≤ 350/uL. Of these, 33% were new diagnoses, and 10% were diagnosed but ART-naive. Men with HIV were almost twice as likely as women with HIV to have CD4 ≤ 350/uL and be untreated (15% vs 8%, respectively). Streamlined care reduced mortality by 28% versus control (risk ratio [RR] = 0.72; 95% confidence interval [CI]: .56, .93; P = .02). Despite eligibility in both arms, persons with CD4 ≤ 350/uL started ART faster under streamlined care versus control (76% vs 43% by 12 months, respectively; P < .001). Mortality was reduced substantially more among men (RR = 0.61; 95% CI: .43, .86; P = .01) than among women (RR = 0.90; 95% CI: .62, 1.32; P = .58)., Conclusions: After population-based HIV testing, streamlined care reduced population-level mortality among persons with HIV and CD4 ≤ 350/uL, particularly among men. Streamlined HIV care models may play a key role in global efforts to reduce AIDS deaths., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda., Methods and Findings: This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care., Conclusions: In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA., Trial Registration: ClinicalTrials.gov NCT01864603., Competing Interests: EDC and his institution have received grants from the NIH and the European & Developing Countries Clinical Trials Partnership (EDCTP). All other authors have declared that no competing interests exist.

Background: The SEARCH study provided community-based HIV and multidisease testing and antiretroviral therapy (ART) to 32 communities in East Africa and reported no statistically significant difference in 3-year HIV incidence. We used mathematical modeling to estimate the effect of control arm viral suppression and community mixing on SEARCH trial outcomes., Setting: Uganda and Kenya., Methods: Using the individual-based HIV modeling software EMOD-HIV, we configured a new model of SEARCH communities. The model was parameterized using demographic, HIV prevalence, male circumcision, and viral suppression data and calibrated to HIV prevalence, ART coverage, and population size. Using assumptions about ART scale-up in the control arm, degree of community mixing, and effect of baseline testing, we estimated comparative HIV incidence under multiple scenarios., Results: Before the trial results, we predicted that SEARCH would report a 4%-40% reduction between arms, depending on control arm ART linkage rates and community mixing. With universal baseline testing followed by rapidly expanded ART eligibility and uptake, modeled effect sizes were smaller than the study was powered to detect. Using interim viral suppression data, we estimated 3-year cumulative incidence would have been reduced by up to 27% in the control arm and 43% in the intervention arm compared with a counterfactual without universal baseline testing., Conclusions: Our model suggests that the active control arm substantially reduced expected effect size and power of the SEARCH study. However, compared with a counterfactual "true control" without increased ART linkage because of baseline testing, SEARCH reduced HIV incidence by up to 43%., Competing Interests: B.L.J., L.B.B., T.D.C, E.D.C., D.K., M.R.K., D.V.H., and M.L.P. have received grant funding paid to her institution from the NIH. Research reported in this article was supported by the Division of AIDS, NIAID of the National Institutes of Health under award numbers U01A1099959 and UM1AI068636 and in part by the President's Emergency Plan for AIDS Relief, the Bill and Melinda Gates Foundation, and Gilead Sciences. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the article. The remaining author has no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Antiretroviral-based HIV prevention, including pre-exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high-risk sexual exposures. Non-occupational post-exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient-centred PEP programme with options for facility- or community-based service delivery., Methods: After population-level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in-country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out-of-facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful "PEP completion" was defined as self-reported adherence over four weeks of therapy with post-PEP HIV testing., Results: Community leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28-day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out-of-facility community-based sites; 35% of participants had ≥1 out-of-facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions., Conclusions: Among individuals with elevated-risk exposures in rural East African communities, patient-centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

HIV-related stigma is a frequently cited barrier to HIV testing and care engagement. A nuanced understanding of HIV-related stigma is critical for developing stigma-reduction interventions to optimize HIV-related outcomes. This qualitative study documented HIV-related stigma across eight communities in east Africa during the baseline year of a large HIV test-and-treat trial (SEARCH, NCT: 01864603), prior to implementation of widespread community HIV testing campaigns and efforts to link individuals with HIV to care and treatment. Findings revealed experiences of enacted, internalized and anticipated stigma that were highly gendered, and more pronounced in communities with lower HIV prevalence; women, overwhelmingly, both held and were targets of stigmatizing attitudes about HIV. Past experiences with enacted stigma included acts of segregation, verbal discrimination, physical violence, humiliation and rejection. Narratives among women, in particular, revealed acute internalized stigma including feelings of worthlessness, shame, embarrassment, and these resulted in anxiety and depression, including suicidality among a small number of women. Anticipated stigma included fears of marital dissolution, verbal and physical abuse, gossip and public ridicule. Anticipated stigma was especially salient for women who held internalized stigma and who had experienced enacted stigma from their partners. Anticipated stigma led to care avoidance, care-seeking at remote facilities, and hiding of HIV medications. Interventions aimed at reducing individual and community-level forms of stigma may be needed to improve the lives of PLHIV and fully realize the promise of test-and-treat strategies., Competing Interests: Gilead Sciences provided tenofovir-emtricitabine (Truvada) in kind. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors do not have any other competing interest to declare.

Background: In the United States, patients with HIV face significant barriers to linkage to and retention in care which impede the necessary steps toward achieving the desired clinical outcome of viral suppression. Individual-level interventions, such as patient navigation, are evidence based, effective strategies for improving care engagement. In addition, use of surveillance and clinical data to identify patients who are not fully engaged in care may improve the effectiveness and cost-effectiveness of these programs., Methods and Findings: We employed a pre-post design to estimate the outcomes and costs, from the program perspective, of 5 state-level demonstration programs funded under the Health Resources and Services Administration's Special Projects of National Significance Program (HRSA/SPNS) Systems Linkages Initiative that employed existing surveillance and/or clinical data to identify individuals who had never entered HIV care, had fallen out of care, or were at risk of falling out of care and navigation strategies to engage patients in HIV care. Outcomes and costs were measured relative to standard of care during the first year of implementation of the interventions (2013 to 2014). We followed patients to estimate the number and proportion of additional patients linked, reengaged, retained, and virally suppressed by 12 months after enrollment in the interventions. We employed inverse probability weighting to adjust for differences in patient characteristics across programs, missing data, and loss to follow-up. We estimated the additional costs expended during the first year of each intervention and the cost per outcome of each intervention as the additional cost per HIV additional care continuum target achieved (cost per patient linked, reengaged, retained, and virally suppressed) 12 months after enrollment in each intervention. In this study, 3,443 patients were enrolled in Louisiana (LA), Massachusetts (MA), North Carolina (NC), Virginia (VA), and Wisconsin (WI) (147, 151, 2,491, 321, and 333, respectively). Patients were a mean of 40 years old, 75% male, and African American (69%) or Caucasian (22%). At baseline, 24% were newly diagnosed, 2% had never been in HIV care, 45% had fallen out of care, and 29% were at risk of falling out of care. All 5 interventions were associated with increases in the number and proportion of patients with viral suppression [percent increase: LA = 90.9%, 95% confidence interval (CI) = 88.4 to 93.4; MA = 78.1%, 95% CI = 72.4 to 83.8; NC = 47.5%, 95% CI = 45.2 to 49.8; VA = 54.6, 95% CI = 49.4 to 59.9; WI = 58.4, 95% CI = 53.4 to 63.4]. Overall, interventions cost an additional $4,415 (range = $3,746 to $5,619), $2,009 (range = $1,516 to $2,274), $920 (range = $627 to $941), $2,212 (range = $1,789 to $2,683), and $3,700 ($2,734 to $4,101), respectively per additional patient virally suppressed. The results of this study are limited in that we did not have contemporaneous controls for each intervention; thus, we are only able to assess patients against themselves at baseline and not against standard of care during the same time period., Conclusions: Patient navigation programs were associated with improvements in engagement of patients in HIV care and viral suppression. Cost per outcome was minimized in states that utilized surveillance data to identify individuals who were out of care and/or those that were able to identify a larger number of patients in need of improvement at baseline. These results have the potential to inform the targeting and design of future navigation-type interventions., Competing Interests: The authors have declared that no competing interests exist.

Objective: Sub-Saharan Africa faces twin epidemics of HIV and noncommunicable diseases including hypertension. Integrating hypertension care into chronic HIV care is a global priority, but cost estimates are lacking. In the SEARCH Study, we performed population-level HIV/hypertension testing, and offered integrated streamlined chronic care. Here, we estimate costs for integrated hypertension/HIV care for HIV-positive individuals, and costs for hypertension care for HIV-negative individuals in the same clinics., Design: Microcosting analysis of healthcare expenditures within Ugandan HIV clinics., Methods: SEARCH (NCT: 01864603) conducted community health campaigns for diagnosis and linkage to care for both HIV and hypertension. HIV-positive patients received hypertension/HIV care jointly including blood pressure monitoring and medications; HIV-negative patients received hypertension care at the same clinics. Within 10 Ugandan study communities during 2015-2016, we estimated incremental annual per-patient hypertension care costs using micro-costing techniques, time-and-motion personnel studies, and administrative/clinical records review., Results: Overall, 70 HIV-positive and 2355 HIV-negative participants received hypertension care. For HIV-positive participants, average incremental cost of hypertension care was $6.29 per person per year, a 2.1% marginal increase over prior estimates for HIV care alone. For HIV-negative participants, hypertension care cost $11.39 per person per year, a 3.8% marginal increase over HIV care costs. Key costs for HIV-positive patients included hypertension medications ($6.19 per patient per year; 98% of total) and laboratory testing ($0.10 per patient per year; 2%). Key costs for HIV-negative patients included medications ($5.09 per patient per year; 45%) and clinic staff salaries ($3.66 per patient per year; 32%)., Conclusion: For only 2-4% estimated additional costs, hypertension care was added to HIV care, and also expanded to all HIV-negative patients in prototypic Ugandan clinics, demonstrating substantial synergy. Our results should encourage accelerated scale-up of hypertension care into existing clinics., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP., Methods and Findings: During population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (<1,000 c/ml based on available assays) after ART start. Using Poisson regression with cluster-robust standard errors, we compared HIV incidence among PrEP initiators to incidence among propensity score-matched recent historical controls (from the year before PrEP availability) in 8 of the 16 communities, adjusted for risk group. Among 74,541 individuals who tested negative for HIV, 15,632/74,541 (21%) were assessed to be at elevated HIV risk; 5,447/15,632 (35%) initiated PrEP (49% female; 29% 15-24 years; 19% in serodifferent partnerships), of whom 79% engaged in ≥1 follow-up visit and 61% self-reported PrEP adherence at ≥1 visit. Over 7,150 person-years of follow-up, HIV incidence was 0.35 per 100 person-years (95% confidence interval [CI] 0.22-0.49) among PrEP initiators. Among matched controls, HIV incidence was 0.92 per 100 person-years (95% CI 0.49-1.41), corresponding to 74% lower incidence among PrEP initiators compared to matched controls (adjusted incidence rate ratio [aIRR] 0.26, 95% CI 0.09-0.75; p = 0.013). Among women, HIV incidence was 76% lower among PrEP initiators versus matched controls (aIRR 0.24, 95% CI 0.07-0.79; p = 0.019); among men, HIV incidence was 40% lower, but not significantly so (aIRR 0.60, 95% CI 0.12-3.05; p = 0.54). Of 25 participants with incident HIV infection (68% women), 7/25 (28%) reported taking PrEP ≤30 days before HIV diagnosis, and 24/25 (96%) started ART. Of those with repeat HIV RNA after ART start, 18/19 (95%) had <1,000 c/ml. One participant with viral non-suppression was found to have transmitted viral resistance, as well as emtricitabine resistance possibly related to PrEP use. Limitations include the lack of contemporaneous controls to assess HIV incidence without PrEP and that plasma samples were not archived to assess for baseline acute infection., Conclusions: Population-level offer of PrEP with rapid start and flexible service delivery was associated with 74% lower HIV incidence among PrEP initiators compared to matched recent controls prior to PrEP availability. HIV infections were significantly lower among women who started PrEP. Universal HIV testing with linkage to treatment and prevention, including PrEP, is a promising approach to accelerate reductions in new infections in generalized epidemic settings., Trial Registration: ClinicalTrials.gov NCT01864603., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CAK has received grant support to institution from the US National Institutes of Health and Gilead Research Scholars Program in HIV. DVH has received grant support from the US National Institutes of Health and study drug donation from Gilead Sciences. CM has received grant support from the US National Institutes of Health, the Stupski Foundation, and the Chan-Zuckerberg Biohub Foundation. LiBB has received grant support from the US National Institutes of Health. VJ has received grant support from the US Centers for Disease Control and Prevention/PEPFAR.

Background: Additional progress towards HIV epidemic control requires understanding who remains at risk of HIV infection in the context of high uptake of universal testing and treatment (UTT). We sought to characterize seroconverters and risk factors in the SEARCH UTT trial (NCT01864603), which achieved high uptake of universal HIV testing and ART coverage in 32 communities of adults (≥15 years) in rural Uganda and Kenya., Methods: In a pooled cohort of 117,114 individuals with baseline HIV negative test results, we described those who seroconverted within 3 years, calculated gender-specific HIV incidence rates, evaluated adjusted risk ratios (aRR) for seroconversion using multivariable targeted maximum likelihood estimation, and assessed potential infection sources based on self-report., Results: Of 704 seroconverters, 63% were women. Young (15-24 years) men comprised a larger proportion of seroconverters in Western Uganda (18%) than Eastern Uganda (6%) or Kenya (10%). After adjustment for other risk factors, men who were mobile [≥1 month of prior year living outside community] (aRR:1.68; 95%CI:1.09,2.60) or who HIV tested at home vs. health fair (aRR:2.44; 95%CI:1.89,3.23) were more likely to seroconvert. Women who were aged ≤24 years (aRR:1.91; 95%CI:1.27,2.90), mobile (aRR:1.49; 95%CI:1.04,2.11), or reported a prior HIV test (aRR:1.34; 95%CI:1.06,1.70), or alcohol use (aRR:2.07; 95%CI:1.34,3.22) were more likely to seroconvert. Among survey responders (N = 607, 86%), suspected infection source was more likely for women than men to be ≥10 years older (28% versus 8%) or a spouse (51% vs. 31%) and less likely to be transactional sex (10% versus 16%)., Conclusion: In the context of universal testing and treatment, additional strategies tailored to regional variability are needed to address HIV infection risks of young women, alcohol users, mobile populations, and those engaged in transactional sex to further reduce HIV incidence rates., Competing Interests: The authors have declared that no competing interests exist.

The Sustainable East Africa Research in Community Health (SEARCH), a universal test and treat (UTT) trial, implemented 'Streamlined Care'-a multicomponent strategy including rapid linkage to care and antiretroviral therapy (ART) start, 3-monthly refills, viral load counseling, and accessible, patient-centered care provision. To understand patient and provider experiences of Streamlined Care to inform future care innovations, we conducted in-depth interviews with patients ( n  = 18) and providers ( n  = 28) at baseline (2014) and follow-up (2015) ( n  = 17 patients; n  = 21 providers). Audio recordings were transcribed, translated, and deductively and inductively coded. Streamlined Care helped to decongest clinic spaces and de-stigmatize human immunodeficiency virus (HIV) care. Patients credited the individualized counselling, provider-assisted HIV status disclosure, and providers' knowledge of patient's drug schedules, availability, and phone call reminders for their care engagement. However, for some, denial (repeated testing to disprove HIV+ results), feeling healthy, limited understanding of the benefits of early ART, and anticipated side-effects, and mistrust of researchers hindered rapid ART initiation. Patients' short and long-term mobility proved challenging for both patients and providers. Providers viewed viral load counselling as a powerful tool to convince otherwise healthy and high-CD4 patients to initiate ART. Patient-centered HIV care models should build on the successes of Streamlined Care, while addressing persistent barriers.#NCT01864683-https://clinicaltrials.gov/ct2/show/NCT01864603.

Background: HIV differentiated service delivery (DSD) models are scaling up in resource-limited settings for stable patients; less is known about DSD outcomes for patients with viremia. We evaluated the effect on viral suppression (VS) of a streamlined care DSD model implemented in the SEARCH randomized universal test and treat trial in rural Uganda and Kenya (NCT:01864603)., Methods: We included HIV-infected adults at baseline (2013) who were country guideline antiretroviral therapy (ART) eligible (prior ART experience or CD4 ≤ 350) with ≥1 HIV clinic visit between 2013 and 2017 in SEARCH communities randomized to intervention (N = 16) or control (N = 16). We assessed the effect of streamlined care in intervention community clinics (patient-centered care, increased appointment spacing, improved clinic access, reminders, and tracking) on VS at 3 years. Analysis was stratified by the baseline care status: ART-experienced with viremia, ART-naïve with CD4 ≤ 350, or ART-experienced with VS., Results: Among 6190 ART-eligible persons in care, year 3 VS was 90% in intervention and 87% in control arms (RR 1.03, 95% CI: 1.01 to 1.06). Among ART-experienced persons with baseline viremia, streamlined care was associated with higher VS (67% vs 47%, RR 1.41, 95% CI: 1.05 to 1.91). Among ART-naïve persons, VS was not significantly higher with streamlined care (83% vs 79%, RR 1.05, 95% CI: 0.95 to 1.16). Among ART-experienced persons with baseline VS, nearly all remained virally suppressed in both arms (97% vs 95%, RR 1.01, 95% CI: 1.00 to 1.03)., Conclusions: Streamlined care was associated with higher viral suppression among ART-experienced patients with viremia in this randomized evaluation of ART-eligible patients who were in care after universal HIV testing.

Background: In generalized epidemic settings, strategies are needed to prioritize individuals at higher risk of human immunodeficiency virus (HIV) acquisition for prevention services. We used population-level HIV testing data from rural Kenya and Uganda to construct HIV risk scores and assessed their ability to identify seroconversions., Methods: During 2013-2017, >75% of residents in 16 communities in the SEARCH study were tested annually for HIV. In this population, we evaluated 3 strategies for using demographic factors to predict the 1-year risk of HIV seroconversion: membership in ≥1 known "risk group" (eg, having a spouse living with HIV), a "model-based" risk score constructed with logistic regression, and a "machine learning" risk score constructed with the Super Learner algorithm. We hypothesized machine learning would identify high-risk individuals more efficiently (fewer persons targeted for a fixed sensitivity) and with higher sensitivity (for a fixed number targeted) than either other approach., Results: A total of 75 558 persons contributed 166 723 person-years of follow-up; 519 seroconverted. Machine learning improved efficiency. To achieve a fixed sensitivity of 50%, the risk-group strategy targeted 42% of the population, the model-based strategy targeted 27%, and machine learning targeted 18%. Machine learning also improved sensitivity. With an upper limit of 45% targeted, the risk-group strategy correctly classified 58% of seroconversions, the model-based strategy 68%, and machine learning 78%., Conclusions: Machine learning improved classification of individuals at risk of HIV acquisition compared with a model-based approach or reliance on known risk groups and could inform targeting of prevention strategies in generalized epidemic settings., Clinical Trials Registration: NCT01864603., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: The rollout of antiretroviral therapy (ART) has been associated with reductions in HIV-related stigma, but pathways through which this reduction occurs are poorly understood. In the newer context of universal test and treat (UTT) interventions, where rapid diffusion of ART uptake takes place, there is an opportunity to understand the processes through which HIV-related stigma can decline, and how UTT strategies may precipitate more rapid and widespread changes in stigma. This qualitative study sought to evaluate how a UTT intervention influenced changes in beliefs, attitudes and behaviours related to HIV., Methods: Longitudinal qualitative in-depth semi-structured interview data were collected within a community-cluster randomized UTT trial, the Sustainable East Africa Research in Community Health (SEARCH) study, annually over three rounds (2014 to 2016) from two cohorts of adults (n = 32 community leaders, and n = 112 community members) in eight rural communities in Uganda and Kenya. Data were inductively analysed to develop new theory for understanding the pathways of stigma decline., Results: We present an emergent theoretical model of pathways through which HIV-related stigma may decline: internalized stigma may be reduced by two processes accelerated through the uptake and successful usage of ART: first, a reduced fear of dying and increased optimism for prolonged and healthy years of life; second, a restoration of perceived social value and fulfilment of subjective role expectations via restored physical strength and productivity. Anticipated stigma may be reduced in response to widespread engagement in HIV testing, leading to an increasing number of HIV status disclosures in a community, "normalizing" disclosure and reducing fears. Improvements in the perceived quality of HIV care lead to people living with HIV (PLHIV) seeking care in nearby facilities, seeing other known community members living with HIV, reducing isolation and facilitating opportunities for social support and "solidarity." Finally, enacted stigma may be reduced in response to the community viewing the healthy bodies of PLHIV successfully engaged in treatment, which lessens the fears that trigger enacted stigma; it becomes no longer socially normative to stigmatize PLHIV. This process may be reinforced through public health messaging and anti-discrimination laws., Conclusions: Declines in HIV-related stigma appear to underway and explained by social processes accelerated by UTT efforts. Widespread implementation of UTT shows promise for reducing multiple dimensions of stigma, which is critical for improving health outcomes among PLHIV., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Population-level estimates of disease prevalence and control are needed to assess prevention and treatment strategies. However, available data often suffer from differential missingness. For example, population-level HIV viral suppression is the proportion of all HIV-positive persons with suppressed viral replication. Individuals with measured HIV status, and among HIV-positive individuals those with measured viral suppression, likely differ from those without such measurements., Methods: We discuss three sets of assumptions to identify population-level suppression in the intervention arm of the SEARCH Study (NCT01864603), a community randomized trial in rural Kenya and Uganda (2013-2017). Using data on nearly 100,000 participants, we compare estimates from (1) an unadjusted approach assuming data are missing-completely-at-random (MCAR); (2) stratification on age group, sex, and community; and (3) targeted maximum likelihood estimation to adjust for a larger set of baseline and time-updated variables., Results: Despite high measurement coverage, estimates of population-level viral suppression varied by identification assumption. Unadjusted estimates were most optimistic: 50% (95% confidence interval [CI] = 46%, 54%) of HIV-positive persons suppressed at baseline, 80% (95% CI = 78%, 82%) at year 1, 85% (95% CI = 83%, 86%) at year 2, and 85% (95% CI = 83%, 87%) at year 3. Stratifying on baseline predictors yielded slightly lower estimates, and full adjustment reduced estimates meaningfully: 42% (95% CI = 37%, 46%) of HIV-positive persons suppressed at baseline, 71% (95% CI = 69%, 73%) at year 1, 76% (95% CI = 74%, 78%) at year 2, and 79% (95% CI = 77%, 81%) at year 3., Conclusions: Estimation of population-level disease burden and control requires appropriate adjustment for missing data. Even in large studies with limited missingness, estimates relying on the MCAR assumption or baseline stratification should be interpreted cautiously.