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

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

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.

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..

A mid-level health manager intervention to promote uptake of isoniazid preventive therapy among people with HIV in Uganda: a cluster randomised trial.

BACKGROUND: Despite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice. METHODS: We conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control groups. Our intervention convened managers into mini-collaboratives facilitated by Ugandan experts in tuberculosis and HIV, and provided business leadership and management training, SMS platform access, and data feedback. The control was standard practice. Participants were not masked to trial group, but study statisticians were masked until trial completion. The primary outcome was IPT initiation rates among adults with HIV in facilities overseen by participants over a period of 2 years (2019-21). We conducted prespecified analyses that excluded the third quarter of 2019 (Q3-2019) to understand intervention effects independent of a national 100-day IPT push tied to a financial contingency during Q3-2019. This trial is registered with ClinicalTrials.gov (NCT03315962), and is ongoing. FINDINGS: Between Nov 15, 2017, and March 14, 2018, managers from 82 of 82 eligible districts (61% of Uganda's 135 districts) were enrolled and randomised: 43 districts to intervention, 39 to control. Intervention delivery took place between Dec 6, 2017, and Feb 2, 2022. Over 2 years, IPT initiation rates were 0·74 versus 0·65 starts per person-year in intervention versus control groups (incidence rate ratio [IRR] 1·14, 95% CI 0·88-1·46; p=0·16). Excluding Q3-2019, IPT initiation was higher in the intervention group versus the control group: 0·32 versus 0·25 starts per person-year (IRR 1·27, 95% CI 1·00-1·61; p=0·026). INTERPRETATION: Following an intervention targeting managers in more than 60% of Uganda's districts, IPT initiation rates were not significantly higher in intervention than control groups. After accounting for large increases in IPT from a 100-day push in both groups, the intervention led to significantly increased IPT rates, sustained after the push and during the COVID-19 pandemic. Our findings suggest that interventions centred on mid-level health managers can improve IPT implementation on a large, subnational scale, and merit further exploration to address key public health challenges for which strong evidence exists but implementation remains suboptimal. FUNDING: National Institute of Allergy and Infectious Diseases.

Understanding the role of incentives for achieving and sustaining viral suppression: A qualitative sub-study of a financial incentives trial in Uganda.

BACKGROUND: Viral suppression among people living with HIV (PLHIV) is essential for protecting health and preventing HIV transmission, yet globally, rates of viral suppression are sub-optimal. Interventions to improve HIV prevention and care cascade outcomes remain vital. Financial incentives hold promise for improving these outcomes, yet to date, clinical trial results have been mixed. METHODS: This qualitative sub-study, embedded in a trial (NCT02890459) in Uganda to test whether incentives are effective for achieving viral suppression in PLHIV, sought to enhance our understanding of the factors that influence this outcome. Forty-nine (n = 49) PLHIV, purposely sampled to balance across gender, study arm, and viral suppression status, were interviewed to explore barriers and motivations for care engagement, adherence, and viral suppression, and attributions for decision-making, including perceived influence of incentives on behaviors. RESULTS: While many participants with undetectable viral load (VL) who received incentives said the incentives motivated their ART adherence, others expressed intrinsic motivation for adherence. All felt that incentives reduced burdens of transport costs, lost income due to time spent away from work, and food insecurity. Incentives may have activated attention and memory for some, as excitement about anticipating incentives helped them adhere to medication schedules. In comparison, participants who were randomized to receive incentives but had detectable VL faced a wider range, complexity and severity of challenges to care engagement. Notably, their narratives included more accounts of poor treatment in clinics, food insecurity, and severe forms of stigma. With or without incentives, adherence was reinforced through experiencing restored health due to ART, social support (especially from partners), and good quality counseling and clinical care. CONCLUSIONS: In considering why incentives sometimes fail to achieve behavior change, it may be helpful to attend to the full set of factors- psychological, interpersonal, social and structural- that militate against the behavior change required to achieve behavioral outcomes. To be effective, incentives may need to be combined with other interventions to address the spectrum of barriers to care engagement.

Provider and Patient Perspectives of Rapid ART Initiation and Streamlined HIV Care: Qualitative Insights From Eastern African Communities.

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.

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.

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.

The Drinkers' Intervention to Prevent Tuberculosis (DIPT) trial among heavy drinkers living with HIV in Uganda: study protocol of a 2×2 factorial trial.

BACKGROUND: The risk of tuberculosis (TB) is high among people with HIV (PWH). Heavy alcohol drinking independently increases TB risk and approximately 25% of PWH globally engage in heavy drinking. While isoniazid (INH) preventive therapy decreases TB incidence and mortality among PWH, heavy drinking during INH is associated with liver toxicity and poor adherence. Interventions are, therefore, urgently needed to decrease alcohol use and improve adherence to INH in this population in settings with high prevalence of HIV and TB like Uganda. METHODS: The Drinkers' Intervention to Prevent TB (DIPT) study is a 2×2 factorial randomized controlled trial among HIV/TB co-infected adults (≥18 years) who engage in heavy alcohol drinking and live in Uganda. The trial will allocate 680 participants with a 1:1:1:1 individual randomization to receive 6 months of INH and one of the following interventions: (1) no incentives (control), (2) financial incentives contingent on low alcohol use, (3) financial incentives contingent on high adherence to INH, and (4) escalating financial incentives for both decreasing alcohol use and increasing adherence to INH. Incentives will be in the form of escalating lottery-based monetary rewards. Participants will attend monthly visits to refill isoniazid medications, undergo liver toxicity monitoring, and, except for controls, determine eligibility for prizes. We will estimate (a) the effect of incentives contingent on low alcohol use on reduction in heavy drinking, measured via a long-term objective and self-reported metric of alcohol use, at 3- and 6-month study visits, and (b) the effect of incentives contingent on high adherence to INH, measured as >90% pill-taking days by medication event monitoring system cap opening. We will use qualitative methods to explore the mechanisms of any influence of financial incentives on HIV virologic suppression. DISCUSSION: This study will provide new information on low-cost strategies to both reduce alcohol use and increase INH adherence among people with HIV and TB infection who engage in heavy drinking in low-income countries with high HIV and TB prevalence. TRIAL REGISTRATION: ClinicalTrials.gov NCT03492216 . Registered on April 10, 2018.

Dimensions of HIV-related stigma in rural communities in Kenya and Uganda at the start of a large HIV 'test and treat' trial.

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.

Costs of integrating hypertension care into HIV care in rural East African clinics.

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.

Predicting HIV Incidence in the SEARCH Trial: A Mathematical Modeling Study.

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%.

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 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.

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).

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.

Planning prompts to promote uptake of HIV services among men: a randomised trial in rural Uganda.

INTRODUCTION: Interventions informed by behavioural economics, such as planning prompts, have the potential to increase HIV testing at minimal or no cost. Planning prompts have not been previously evaluated for HIV testing uptake. We conducted a randomised clinical trial to evaluate the effectiveness of low-cost planning prompts to promote HIV testing among men. METHODS: We randomised adult men in rural Ugandan parishes to receive a calendar planning prompt that gave them the opportunity to make a plan to get tested for HIV at health campaigns held in their communities. Participants received either a calendar showing the dates when the community health campaign would be held (control group) or a calendar showing the dates and prompting them to select a date and time when they planned to attend (planning prompt group). Participants were not required to select a date and time or to share their selection with study staff. The primary outcome was HIV testing uptake at the community health campaign. RESULTS: Among 2362 participants, 1796 (76%) participants tested for HIV. Men who received a planning prompt were 2.2 percentage points more likely to test than the control group, although the difference was not statistically significant (77.1% vs 74.9%; 95% CI -1.2 to 5.7 percentage points, p=0.20). The planning prompt was more effective among men enrolled ≤40 days before the campaigns (3.6 percentage-point increase in testing; 95% CI -2.9 to 10.1, p=0.27) than among men enrolled >40 days before the campaigns (1.8 percentage-point increase; 95% CI -2.3 to 5.8, p=0.39), although the effects within the subgroups were not significant. CONCLUSION: These findings suggest that planning prompts may be an effective behavioural intervention to promote HIV testing at minimal or no cost. Large-scale studies should further assess the impact and cost-effectiveness of such interventions.

Pathways for reduction of HIV-related stigma: a model derived from longitudinal qualitative research in Kenya and Uganda.

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.

Improved Viral Suppression With Streamlined Care in the SEARCH Study.

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.

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.