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

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

Feasibility and preliminary effectiveness of integrating HIV prevention into an adolescent empowerment and livelihood intervention at youth clubs in rural Uganda.

The uptake of HIV prevention services is lower among youth than adults in sub-Saharan Africa. Existing youth livelihood trainings offer a potential entry point to HIV prevention services. We determined feasibility and preliminary effectiveness of integrating HIV prevention into youth clubs implementing an empowerment and livelihood for adolescents (ELA) intervention in rural Uganda. Staff conducted community mobilization for youth (15-24 years) over one month. Clubs met (3×/week) over six months, with local peer mentors trained to teach life-skills and sexual/reproductive health education. We integrated mentor-led education on HIV prevention, including pre- and post-exposure prophylaxis (PrEP/PEP). Clubs offered on-site HIV testing, a field trip to a local clinic and PrEP referrals after one month and six months. Surveys were conducted at baseline and six months. Forty-two participants (24 adolescent girls/young women (AGYW) and 18 adolescent boys/young men (ABYM)) joined the clubs. At baseline, no participants accepted referral for PrEP, whereas 5/18 (28%) sexually active, HIV-negative AGYW requested PrEP referral at follow-up. One ABYM requested PEP referral. Integration of HIV prevention services into an established ELA curriculum at mentor-led youth clubs in rural Uganda was feasible. PrEP uptake increased among sexually active AGYW. Evaluation of this approach for HIV prevention among youth merits further study.

HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa.

BACKGROUND: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health. METHODS: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only). RESULTS: A total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 person-years; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39). CONCLUSIONS: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.).

Higher Levels of Alcohol Use Are Associated With Latent Tuberculosis Infection in Adults Living With Human Immunodeficiency Virus.

We assessed associations between hazardous alcohol use and latent tuberculosis infection (LTBI) among adults living with human immunodeficiency virus (HIV) in Uganda. We compared tuberculin skin test positivity across medium, high, and very-high alcohol use levels, classified by AUDIT-C scores. In multivariable analysis, very high use was associated with LTBI (adjusted odds ratio 1.61, 95% confidence interval: 1.03-2.50).

Financial incentives and deposit contracts to promote HIV retesting in Uganda: A randomized trial.

BACKGROUND: Frequent retesting for HIV among persons at increased risk of HIV infection is critical to early HIV diagnosis of persons and delivery of combination HIV prevention services. There are few evidence-based interventions for promoting frequent retesting for HIV. We sought to determine the effectiveness of financial incentives and deposit contracts in promoting quarterly HIV retesting among adults at increased risk of HIV. METHODS AND FINDINGS: In peri-urban Ugandan communities from October to December 2018, we randomized HIV-negative adults with self-reported risk to 1 of 3 strategies to promote HIV retesting: (1) no incentive; (2) cash incentives (US$7) for retesting at 3 and 6 months (total US$14); or (3) deposit contracts: participants could voluntarily deposit US$6 at baseline and at 3 months that would be returned with interest (total US$7) upon retesting at 3 and 6 months (total US$14) or lost if participants failed to retest. The primary outcome was retesting for HIV at both 3 and 6 months. Of 1,482 persons screened for study eligibility following community-based recruitment, 524 participants were randomized to either no incentive (N = 180), incentives (N = 172), or deposit contracts (N = 172): median age was 25 years (IQR: 22 to 30), 44% were women, and median weekly income was US$13.60 (IQR: US$8.16 to US$21.76). Among participants randomized to deposit contracts, 24/172 (14%) made a baseline deposit, and 2/172 (1%) made a 3-month deposit. In intent-to-treat analyses, HIV retesting at both 3 and 6 months was significantly higher in the incentive arm (89/172 [52%]) than either the control arm (33/180 [18%], odds ratio (OR) 4.8, 95% CI: 3.0 to 7.7, p < 0.001) or the deposit contract arm (28/172 [16%], OR 5.5, 95% CI: 3.3 to 9.1, p < 0.001). Among those in the deposit contract arm who made a baseline deposit, 20/24 (83%) retested at 3 months; 11/24 (46%) retested at both 3 and 6 months. Among 282 participants who retested for HIV during the trial, three (1%; 95%CI: 0.2 to 3%) seroconverted: one in the incentive group and two in the control group. Study limitations include measurement of retesting at the clinic where baseline enrollment occurred, only offering clinic-based (rather than community-based) HIV retesting and lack of measurement of retesting after completion of the trial to evaluate sustained retesting behavior. CONCLUSIONS: Offering financial incentives to high-risk adults in Uganda resulted in significantly higher HIV retesting. Deposit contracts had low uptake and overall did not increase retesting. As part of efforts to increase early diagnosis of HIV among high-risk populations, strategic use of incentives to promote retesting should receive greater consideration by HIV programs. TRIAL REGISTRATION: clinicaltrials.gov: NCT02890459.

Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda.

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.

HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda.

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.

Social Networks and HIV Care Outcomes in Rural Kenya and Uganda.

BACKGROUND: Social isolation among HIV-positive persons might be an important barrier to care. Using data from the SEARCH Study in rural Kenya and Uganda, we constructed 32 community-wide, sociocentric networks and evaluated whether less socially connected HIV-positive persons were less likely to know their status, have initiated treatment, and be virally suppressed. METHODS: Between 2013 and 2014, 168,720 adult residents in the SEARCH Study were census-enumerated, offered HIV testing, and asked to name social contacts. Social networks were constructed by matching named contacts to other residents. We characterized the resulting networks and estimated risk ratios (aRR) associated with poor HIV care outcomes, adjusting for sociodemographic factors and clustering by community with generalized estimating equations. RESULTS: The sociocentric networks contained 170,028 residents (nodes) and 362,965 social connections (edges). Among 11,239 HIV-positive persons who named ≥1 contact, 30.9% were previously undiagnosed, 43.7% had not initiated treatment, and 49.4% had viral nonsuppression. Lower social connectedness, measured by the number of persons naming an HIV-positive individual as a contact (in-degree), was associated with poorer outcomes in Uganda, but not Kenya. Specifically, HIV-positive persons in the lowest connectedness tercile were less likely to be previously diagnosed (Uganda-West aRR: 0.89 [95% confidence interval (CI): 0.83, 0.96]; Uganda-East aRR: 0.85 [95% CI: 0.76, 0.96]); on treatment (Uganda-West aRR: 0.88 [95% CI: 0.80, 0.98]; Uganda-East aRR: 0.81 [0.72, 0.92]), and suppressed (Uganda-West aRR: 0.84 [95% CI: 0.73, 0.96]; Uganda-East aRR: 0.74 [95% CI: 0.58, 0.94]) than those in the highest connectedness tercile. CONCLUSIONS: HIV-positive persons named as a contact by fewer people may be at higher risk for poor HIV care outcomes, suggesting opportunities for targeted interventions.

HIV retesting and risk behaviors among high-risk, HIV-uninfected adults in Uganda.

There are limited data characterizing HIV retesting among high-risk adults in sub-Saharan Africa. From October-December 2018, we distributed recruitment cards offering health evaluations with HIV testing at venues frequented by individuals at-risk of HIV infection in Southwest Uganda. Those who attended were asked about their HIV testing history and risk factors: having >1 sexual partner, an HIV+ partner, STIs, and/or transactional sex. We defined "highest risk" as ≥3 risk factors and "frequent testing" as ≥3 tests within the past year. Of 1,777 cards distributed, 1,482 (83%) adults came to clinic: median age was 26(IQR: 22-31), 598 (40%) were men, and 334 (23%) were HIV+. Of 1,148 HIV-negative adults, 338 (29%) were highest risk and 205 (18%) were frequent testers. Frequent testing was similar in women (19%) and men (16%, p = 0.22). Among women, those at highest risk were more likely to report any testing (90% vs. 81%, p = 0.01) and frequent testing (25% vs. 18%, p = 0.06) than those at lower risk. Among men, any testing and frequent testing were similar between risk levels. Among adults recruited from high-risk venues in peri-urban Uganda, HIV risk behaviors were commonly reported, yet frequent retesting remained low. Interventions to promote retesting are needed, particularly among men.

Machine Learning to Identify Persons at High-Risk of Human Immunodeficiency Virus Acquisition in Rural Kenya and Uganda.

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.

Far from MCAR: Obtaining Population-level Estimates of HIV Viral Suppression.

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.

Universal HIV Testing and Treatment (UTT) Integrated with Chronic Disease Screening and Treatment: the SEARCH study.

PURPOSE OF REVIEW: The growing burden of untreated chronic disease among persons with HIV (PWH) threatens to reverse heath gains from ART expansion. Universal test and treat (UTT)'s population-based approach provides opportunity to jointly identify and treat HIV and other chronic diseases. This review's purpose is to describe SEARCH UTT study's integrated disease strategy and related approaches in Sub-Saharan Africa. RECENT FINDINGS: In SEARCH, 97% of adults were HIV tested, 85% were screened for hypertension, and 79% for diabetes at health fairs after 2 years, for an additional $1.16/person. After 3 years, population-level hypertension control was 26% higher in intervention versus control communities. Other mobile/home-based multi-disease screening approaches have proven successful, but data on multi-disease care delivery are extremely limited and show little effect on clinical outcomes. Integration of chronic disease into HIV in the UTT era is feasible and can achieve population level effects; however, optimization and implementation remain a huge unmet need.

Men's Beliefs About the Likelihood of Serodiscordance in Couples with an HIV-Positive Partner: Survey Evidence from Rural Uganda.

Few studies in sub-Saharan Africa have assessed men's knowledge about the likelihood of serodiscordance in couples with an HIV-positive partner and how this is affected by antiretroviral therapy (ART). Using a Likert scale and probabilistic scale, we elicited beliefs of 2532 rural Ugandan men about the likelihood of seroconcordance in married couples with an HIV-positive female partner who is either taking ART or not taking ART. Logistic regression analyses explored associations between beliefs and various health behaviors. Probabilistic scale responses were consistent with Likert scale responses. Seroconcordance was believed to be likely in the scenarios without ART and with ART, with mean seroconcordance likelihood of 8.1 and 6.6, respectively, on a scale of 0-10. The majority of participants (57%) believed the likelihood of seroconcordance was lower in the scenario with ART. The results suggest a need for enhanced education among men about serodiscordance in stable relationships and about the preventive effects of ART.

Understanding Demand for PrEP and Early Experiences of PrEP Use Among Young Adults in Rural Kenya and Uganda: A Qualitative Study.

Few studies have sought to understand factors influencing uptake and continuation of pre-exposure prophylaxis (PrEP) among young adults in sub-Saharan Africa in the context of population-based delivery of open-label PrEP. To address this gap, this qualitative study was implemented within the SEARCH study (NCT#01864603) in Kenya and Uganda, which achieved near-universal HIV testing, and offered PrEP in 16 intervention communities beginning in 2016-2017. Focus group discussions (8 groups, n = 88 participants) and in-depth interviews (n = 23) with young adults who initiated or declined PrEP were conducted in five communities, to explore PrEP-related beliefs and attitudes, HIV risk perceptions, motivations for uptake and continuation, and experiences. Grounded theoretical methods were used to analyze data. Young people felt personally vulnerable to HIV, but perceived the severity of HIV to be low, due to the success of antiretroviral therapy (ART): daily pill-taking was more threatening than the disease itself. Motivations for PrEP were highly gendered: young men viewed PrEP as a vehicle for safely pursuing multiple partners, while young women saw PrEP as a means to control risks in the context of engagement in transactional sex and limited agency to negotiate condom use and partner testing. Rumors, HIV/ART-related stigma, and desire for "proof" of efficacy militated against uptake, and many women required partners' permission to take PrEP. Uptake was motivated by high perceived HIV risk, and beliefs that PrEP use supported life goals. PrEP was often discontinued due to dissolution of partnerships/changing risk, unsupportive partners/peers, or early side effects/pill burden. Despite high perceived risks and interest, PrEP was received with moral ambivalence because of its associations with HIV/ART and stigmatized behaviors. Delivery models that promote youth access, frame messaging on wellness and goals, and foster partner and peer support, may facilitate uptake among young people.

Predictors of isoniazid preventive therapy completion among HIV-infected patients receiving differentiated and non-differentiated HIV care in rural Uganda.

Rates of Isoniazid Preventive Therapy (IPT) completion remain low in programmatic settings in sub-Saharan Africa. Differentiated HIV care models may improve IPT completion by addressing joint barriers to IPT and HIV treatment. However, the impact of differentiated care on IPT completion remains unknown. In a cross-sectional study of people with HIV on antiretroviral therapy in 5 communities in rural Uganda, we compared IPT completion between patients receiving HIV care via a differentiated care model versus a standard HIV care model and assessed multi-level predictors of IPT completion. A total of 103/144 (72%) patients received differentiated care and 85/161 (53%) received standard care completed IPT (p < 0.01). Adjusting for age, gender and community, patients receiving differentiated care had higher odds of completing IPT (aOR: 2.6, 95% CI: 1.5-4.5, p < 0.01). Predictors of IPT completion varied by the care model, and differentiated care modified the positive association between treatment completion and the belief in the efficacy of IPT and the negative association with side-effects. Patients receiving a multi-component differentiated care model had a higher odds of IPT completion than standard care, and the model's impact on health beliefs, social support, and perceived side effects to IPT may underlie this positive association.

Leveraging incentives to increase HIV testing uptake among men: qualitative insights from rural Uganda.

BACKGROUND: Few studies have explored how economic incentives influence behavioral outcomes. This study aimed to identify pathways of action of an incentives-based intervention to increase men's participation in HIV testing. METHODS: The qualitative study was embedded in a randomized-controlled trial that compared effectiveness of gain-framed, loss-framed and lottery-based incentives to increase HIV testing among men. Following testing at a community health campaign, 60 in-depth interviews were conducted with men systematically sampled on the basis of age, incentive group, and campaign attendance. Data were coded deductively and inductively for thematic content analysis. RESULTS: Incentives addressed men's structural, interpersonal and individual-level barriers to testing: offered at convenient locations, incentives offset costs of testing, in lost wages, which are exacerbated when livelihoods required mobility. Interpersonal barriers included anticipated stigma/fear of disclosure, social obligations, and negative peer influences. Providing incentives in public settings provided "social proof" that prizes could be won, and facilitated social support and positive norms by promoting testing with trusted others. Incentives had little influence when men appraised prize values to be low, disbelieved they would win a prize, or were already intrinsically motivated to test. Yet, incentives provided a behavioral 'cue to action' for many men who perceived themselves to be susceptible to HIV and perceived HIV disease to be severe, acting as secondary motivator for testing that "sweetened the deal". CONCLUSION: Incentives can be an important 'lever' to promote men's healthy behaviors in resource-poor settings. HIV testing in convenient, public settings, when paired with incentives, provides multiple pathways to stimulate men's testing uptake. TRIAL REGISTRATION: Registered with ClinicalTrials.gov on 08/10/2016, ID: NCT02890459. The first participant was enrolled on 11th April 2016.

Hypertension control in integrated HIV and chronic disease clinics in Uganda in the SEARCH study.

BACKGROUND: There is an increasing burden of hypertension (HTN) across sub-Saharan Africa where HIV prevalence is the highest in the world, but current care models are inadequate to address the dual epidemics. HIV treatment infrastructure could be leveraged for the care of other chronic diseases, including HTN. However, little data exist on the effectiveness of integrated HIV and chronic disease care delivery systems on blood pressure control over time. METHODS: Population screening for HIV and HTN, among other diseases, was conducted in ten communities in rural Uganda as part of the SEARCH study (NCT01864603). Individuals with either HIV, HTN, or both were referred to an integrated chronic disease clinic. Based on Uganda treatment guidelines, follow-up visits were scheduled every 4 weeks when blood pressure was uncontrolled, and either every 3 months, or in the case of drug stock-outs more frequently, when blood pressure was controlled. We describe demographic and clinical variables among all patients and used multilevel mixed-effects logistic regression to evaluate predictors of HTN control. RESULTS: Following population screening (2013-2014) of 34,704 adults age ≥ 18 years, 4554 individuals with HTN alone or both HIV and HTN were referred to an integrated chronic disease clinic. Within 1 year 2038 participants with HTN linked to care and contributed 15,653 follow-up visits over 3 years. HTN was controlled at 15% of baseline visits and at 46% (95% CI: 44-48%) of post-baseline follow-up visits. Scheduled visit interval more frequent than clinical indication among patients with controlled HTN was associated with lower HTN control at the subsequent visit (aOR = 0.89; 95% CI 0.79-0.99). Hypertension control at follow-up visits was higher among HIV-infected patients than uninfected patients to have controlled blood pressure at follow-up visits (48% vs 46%; aOR 1.28; 95% CI 0.95-1.71). CONCLUSIONS: Improved HTN control was achieved in an integrated HIV and chronic care model. Similar to HIV care, visit frequency determined by drug supply chain rather than clinical indication is associated with worse HTN control. TRIAL REGISTRATION: The SEARCH Trial was prospectively registered with ClinicalTrials.gov : NCT01864603.

Early Adopters of Human Immunodeficiency Virus Preexposure Prophylaxis in a Population-based Combination Prevention Study in Rural Kenya and Uganda.

Background: Global guidelines recommend preexposure prophylaxis (PrEP) for individuals with substantial human immunodeficiency virus (HIV) risk. Data on PrEP uptake in sub-Saharan Africa outside of clinical trials are limited. We report on "early adopters" of PrEP in the Sustainable East Africa Research in Community Health (SEARCH) study in rural Uganda and Kenya. Methods: After community mobilization and PrEP education, population-based HIV testing was conducted. HIV-uninfected adults were offered PrEP based on an empirically derived HIV risk score or self-identified HIV risk (if not identified by score). Using logistic regression, we analyzed predictors of early PrEP adoption (starting PrEP within 30 days vs delayed/no start) among adults identified for PrEP. Results: Of 21212 HIV-uninfected adults in 5 communities, 4064 were identified for PrEP (2991 by empiric risk score, 1073 by self-identified risk). Seven hundred and thirty nine individuals started PrEP within 30 days (11% of those identified by risk score; 39% of self-identified); 77% on the same day. Among adults identified by risk score, predictors of early adoption included male sex (adjusted odds ratio 1.53; 95% confidence interval, 1.09-2.15), polygamy (1.92; 1.27-2.90), serodiscordant spouse (3.89; 1.18-12.76), self-perceived HIV risk (1.66; 1.28-2.14), and testing at health campaign versus home (5.24; 3.33-8.26). Among individuals who self-identified for PrEP, predictors of early adoption included older age (2.30; 1.29-4.08) and serodiscordance (2.61; 1.01-6.76). Conclusions: Implementation of PrEP incorporating a population-based empiric risk score, self-identified risk, and rapid initiation, is feasible in rural East Africa. Strategies are needed to overcome barriers to PrEP uptake, particularly among women and youth. Clinical Trials Registration: NCT01864603.

Community-wide Prevalence of Malaria Parasitemia in HIV-Infected and Uninfected Populations in a High-Transmission Setting in Uganda.

BACKGROUND: Malaria control strategies depend on identifying individuals with parasitemia, who may be asymptomatic but retain the ability to transmit disease. Population-level survey data on parasitemia are limited and traditionally exclude adults and human immunodeficiency virus (HIV)-infected individuals. METHODS: We performed a cross-sectional survey of residents aged 18 months to 94 years in Nankoma, Uganda. Blood specimens were collected using the dried blood spot technique from 9629 residents (87.6%), and samples from a subset of 4131 were tested for malaria parasites, using loop-mediated isothermal amplification. Population-level prevalence was estimated using a weighted proportion, and predictors of parasitemia were identified using a multivariate Poisson regression model. RESULTS: The community prevalence of parasitemia was 83.8% (95% confidence interval [CI], 82.9%-84.6%). Parasite prevalence was highest among children aged 5-14 years (94.7%) and lowest among adults (61.9%). In analysis that controlled for age, HIV-infected individuals with an undetectable viral load had a lower risk of parasitemia, compared with HIV-uninfected individuals (adjusted relative risk, 0.16; 95% CI, .10-.27; P < .001). CONCLUSIONS: In a rural Ugandan community, 2 years after distribution of long-lasting insecticide-treated bed nets, the prevalence of malaria parasitemia was high across all ages, peaking in school-aged children. Persons with well-controlled HIV infection had a lower risk of parasitemia, presumably reflecting access to HIV care.

Men "missing" from population-based HIV testing: insights from qualitative research.

Men's uptake of HIV testing is critical to the success of "test and treat" strategies in generalized epidemics. This study sought to identify cultural factors and community processes that influence men's HIV testing uptake in the baseline year of an ongoing test-and-treat trial among 334,479 persons in eastern Africa (SEARCH, NCT#01864603). Data were collected using participant observation at mobile community health campaigns (CHCs) (n = 28); focus group discussions (n = 8 groups) with CHC participants; and in-depth interviews with care providers (n = 50), leaders (n = 32), and members (n = 112) of eight communities in Kenya and Uganda. An 8-person research team defined analytical codes and iteratively refined them during data collection using grounded theoretical approaches, and textual data were coded using Atlas.ti software. Structural and cultural barriers, including men's mobility and gender norms valorizing risk-taking and discouraging health-seeking behavior, were observed, and contributed to men's lower participation in HIV testing relative to women. Men's labor opportunities often require extended absences from households: during planting season, men guarded fields from monkeys from dawn until nightfall; lake fishermen traveled long distances and circulated between beaches. Men often tested "by proxy", believing their wives' HIV test results to be their status. Debates about HIV risks were vigorous, with many men questioning "traditional" masculine gender norms that enhanced risks. The promise of antiretroviral therapy (ART) to prolong health was a motivating factor for many men to participate in testing. Flexibility in operating hours of HIV testing including late evening and weekend times along with multiple convenient locations that moved were cited as facilitating factors enhancing male participating in HIV testing. Mobile testing reduced but did not eliminate barriers to men's participation in a large-scale "test & treat" effort. However, transformations in gender norms related to HIV testing and care-seeking are underway in eastern Africa and should be supported.