Browsing by Author "Ayieko, James"
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Item The Age-specific Burden and Household and School-Based Predictors of Child and Adolescent Tuberculosis Infection in Rural Uganda(PloS one, 2020) Mwangwa, Florence; Charlebois, Edwin D.; Ayieko, James; Olio, Winter; Kwarisiima, Dalsone; Kabami, Jane; Kapogiannis, Bill; Kamya, Moses R.; Havlir, Diane V.; Ruel, Theodore D.The age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection. From 2015–2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5–11 years old) and adolescents (12–19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities. TB infection was defined as a positive TST (induration ≥10mm or ≥5mm if living with HIV). Age-specific prevalence was estimated using inverse probability weighting to adjust for incomplete measurement. Generalized estimating equations were used to assess the association between TB infection and multi-level predictors. The adjusted prevalence of TB infection was 8.5% (95%CI: 6.9–10.4) in children and 16.7% (95% CI:14.0–19.7) in adolescents. Nine percent of children and adolescents with a prevalent TB infection had a household TB contact. Among children, having a household TB contact was strongly associated with TB infection (aOR 5.5, 95% CI: 1.7–16.9), but the strength of this association declined among adolescents and did not meet significance (aOR 2.3, 95% CI: 0.8–7.0). The population attributable faction of TB infection due to a household TB contact was 8% for children and 4% among adolescents. Mobile children and adolescents who travel outside of their community for school had a 1.7 (95% CI 1.0–2.9) fold higher odds of TB infection than those who attended school in the community. Children and adolescents in this area of rural eastern Uganda suffer a significant burden of TB. The majority of TB infections are not explained by a known household TB contact. Our findings underscore the need for community-based TB prevention interventions, especially among mobile youth.Item Association of Implementation of a Universal Testing and Treatment Intervention With HIV Diagnosis, Receipt of Antiretroviral Therapy, and Viral Suppression in East Africa(Jama, 2017) Maya, Petersen; Balzer, Laura; Kwarsiima, Dalsone; Ayieko, James; Kabami, Jane; Owaraganise, Asiphas; Mwangwa, Florence; Kadede, Kevin; Bukusi, Elizabeth A.; Tamara, D. Clark; Charlebois, Edwin; Kamya, Moses; Havlir, DianeAntiretroviral treatment (ART) is now recommended for all HIV-positive persons. UNAIDS has set global targets to diagnose 90% of HIV-positive individuals, treat 90% of diagnosed individuals with ART, and suppress viral replication among 90% of treated individuals, for a population-level target of 73% of all HIV-positive persons with HIV viral suppression. To describe changes in the proportions of HIV-positive individuals with HIV viral suppression, HIV-positive individuals who had received a diagnosis, diagnosed individuals treated with ART, and treated individuals with HIV viral suppression, following implementation of a community-based testing and treatment program in rural East Africa. Observational analysis based on interim data from 16 rural Kenyan (n = 6) and Ugandan (n = 10) intervention communities in the SEARCH Study, an ongoing cluster randomized trial. Community residents who were 15 years or older (N = 77 774) were followed up for 2 years (2013-2014 to 2015-2016). HIV serostatus and plasma HIV RNA level were measured annually at multidisease health campaigns followed by home-based testing for nonattendees. All HIV-positive individuals were offered ART using a streamlined delivery model designed to reduce structural barriers, improve patient-clinician relationships, and enhance patient knowledge and attitudes about HIV. Primary outcome was viral suppression (plasma HIV RNA<500 copies/mL) among all HIV-positive individuals, assessed at baseline and after 1 and 2 years. Secondary outcomes included HIV diagnosis, ART among previously diagnosed individuals, and viral suppression among those who had initiated ART. Among 77 774 residents (male, 45.3%; age 15-24 years, 35.1%), baseline HIV prevalence was 10.3% (7108 of 69 283 residents). The proportion of HIV-positive individuals with HIV viral suppression at baseline was 44.7% (95% CI, 43.5%-45.9%; 3464 of 7745 residents) and after 2 years of intervention was 80.2% (95% CI, 79.1%-81.2%; 5666 of 7068 residents), an increase of 35.5 percentage points (95% CI, 34.4-36.6). After 2 years, 95.9% of HIV-positive individuals had been previously diagnosed (95% CI, 95.3%-96.5%; 6780 of 7068 residents); 93.4% of those previously diagnosed had received ART (95% CI, 92.8%-94.0%; 6334 of 6780 residents); and 89.5% of those treated had achieved HIV viral suppression (95% CI, 88.6%-90.3%; 5666 of 6334 residents). Among individuals with HIV in rural Kenya and Uganda, implementation of community-based testing and treatment was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy. In these communities, the UNAIDS population-level viral suppression target was exceeded within 2 years after program implementation.Item Characteristics of HIV Seroconverters in the Setting of Universal Test and Treat: Results from the SEARCH trial in rural Uganda and Kenya(PloS one, 2021) Nyabuti, Marilyn N.; Maya, L. Petersen; Bukusi, Elizabeth A.; Kamya, Moses R.; Mwangwa, Florence; Kabami, Jane; Charlebois, Edwin D.; Tamara, D. Clark; Chamie, Gabriel; Havlir, Diane V.; Ayieko, JamesAdditional 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. 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. 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%). 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.Item Early Adopters of Human Immunodeficiency Virus Pre-exposure Prophylaxis in a Population-based Combination Prevention Study in Rural Kenya and Uganda(Clinical Infectious Diseases, 2018) Koss, Catherine A.; Ayieko, James; Mwangwa, Florence; Owaraganise, Asiphas; Kwarisiima, Dalsone; Kabami, Jane; Bukusi, Elizabeth A.; Charlebois, Edwin D.; Petersen, Maya L.; Kamya, Moses R.; Havlir, Diane V.; for the SEARCH CollaborationGlobal 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. 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. 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). 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.Item Gaps in the Child Tuberculosis Care Cascade in 32 Rural Communities in Uganda and Kenya(Journal of clinical tuberculosis and other mycobacterial diseases, 2017) Mwangwa, Florence; Chamie, Gabriel; Kwarisiima, Dalsone; Ayieko, James; Owaraganise, Asiphas; Tamara, D. Clark; Bukusi, Elizabeth A.; Kamya, Moses R.; Charlebois, Edwin D.; Marquez, CarinaReducing tuberculosis (TB) deaths among children requires a better understanding of the gaps in the care cascade from TB diagnosis to treatment completion. We sought to assess the child TB care cascade in 32 rural communities in Uganda and Kenya using programmatic data. This is a retrospective cohort study of 160,851 children (ages < 15 years) living in 12 rural communities in Kenya and 22 in Uganda. We reviewed national TB registries from health centers in and adjacent to the 32 communities, and we included all child TB cases recorded from January 1, 2013 to June 30, 2016. To calculate the first step of the child TB care cascade, the number of children with active TB, we divided the number of reported child TB diagnoses by the 2015 World Health Organization (WHO) child TB case detection ratio for Africa of 27%. The remaining components of the Child TB Care Cascade were ascertained directly from the TB registries and included: diagnosed with TB, started on TB treatment, and completed TB treatment. In two and a half years, a total of 42 TB cases were reported among children living in 32 rural communities in Uganda and Kenya. .40% of the children were co-infected with HIV. Using the WHO child TB case detection ratio, we calculated that 155 children in this cohort had TB during the study period. Of those 155 children, 42 were diagnosed and linked to TB care, 42 were started on treatment, and 31 completed treatment. Among the 42 children who started TB treatment, reasons for treatment non-completion were loss to follow up (7%), death (5%), and un-recorded reasons (5%). Overall, 20% (31/155) of children completed the child TB care cascade. In 32 rural communities in Uganda and Kenya, we estimate that 80% of children with TB fell off the care cascade. Reducing morbidity and mortality from child TB requires strengthening of the child TB care cascade from diagnosis through treatment completion.Item High Levels of Retention in Care with Streamlined Care and Universal Test-and-Treat in East Africa(AIDS, 2016) Brown, Lillian B.; Havlir, Diane V.; Ayieko, James; Mwangwa, Florence; Owaraganise, Asiphas; Kwarisiima, Dalsone; Tamara, Clark; Bukusi, Elizabeth A.; Kamya, Moses R.; Petersen, Maya L.; Charlebois, Edwin D.; The Search CollaborationWe sought to measure retention in care and identify predictors of non-retention among patients receiving ART with streamlined delivery during the first year of the ongoing SEARCH “test-and-treat” trial (NCT 01864603) in rural Uganda and Kenya. Prospective cohort of patients in the intervention arm of the SEARCH Study. We measured retention in care at 12 months among HIV-infected adults who linked to care and were offered ART regardless of CD4 cell count, following community-wide HIV-testing. Kaplan-Meier estimates and Cox proportional hazards modeling were used to calculate the probability of retention at one year and identify predictors of non-retention. Among 5,683 adults (age ≥ 15) who linked to care, 95.5% (95% CI: 92.9 – 98.1%) were retained in care at 12 months. The overall probability of retention at one year was 89.3% (95% CI: 87.6 – 90.7%) among patients newly linking to care and 96.4% (95% CI: 95.8 – 97.0%) among patients previously in care. Younger age and pre-ART CD4 below country treatment initiation guidelines were predictors of non-retention among all patients. Among those newly linking, taking more than 30 days to link to care after HIV diagnosis was additionally associated with non-retention at one year. HIV viral load suppression at 12 months was observed in 4,227/4736 (89%) of patients retained with valid viral load results. High retention in care and viral suppression after 1 year were achieved in a streamlined HIV care delivery system in the context of a universal test-and-treat intervention.Item Isoniazid Preventive Therapy Completion in the Era of Differentiated HIV Care(Journal of acquired immune deficiency syndromes, 2017) Tram, Khai Hoan; Mwangwa, Florence; Atukunda, Mucunguzi; Owaraganise, Asiphas; Ayieko, James; Plenty, Albert; Kwariisima, Dalsone; Tamara, D. Clark; Maya, L. Petersen; Charlebois, Edwin D.; Kamya, Moses R.; Chamie, Gabriel; Havlir, Diane V.; Marquez, Carina; The Search CollaborationIsoniazid preventive therapy (IPT) reduces incidence of TB by up to 60% and reduces mortality among people living with HIV (PLWH),1–4 but implementation of IPT remains poor. In East Africa, use of IPT by patients in HIV care ranges from 0.5% in Uganda to 19% in Kenya.5 Even where IPT programs are implemented, completion rates in East Africa range between 36–98%.6–11 Countries in sub-Saharan Africa are scaling up both IPT and differentiated HIV care, but there is little data to guide optimal integration of IPT into differentiated HIV care models. In differentiated HIV care stable patients typically receive quarterly ART refills either in a clinic or via community adherence groups to enhance retention in care and to decongest clinics.12,13 This less frequent scheduling is at odds with guideline recommended monthly IPT visit frequencies and could challenge successful IPT completion. To our knowledge, there are no studies assessing IPT treatment completion in the setting of well-engaged patients receiving differentiated HIV care. As such, we sought to characterize (1) baseline IPT completion rates and (2) predictors of IPT completion among HIV-infected adults, with a high rate of virologic suppression, who were receiving differentiated HIV care in 5 rural clinics in Uganda. These patients were accustomed to quarterly visits for ART refills, but to receive IPT, had to increase their visit frequency to monthly.Item Predictors of Isoniazid Preventive Therapy Completion Among HIV-Infected Patients Receiving Differentiated and non-Differentiated HIV Care in Rural Uganda(AIDS care, 2020) Tram, Khai Hoan; Mwangwa, Florence; Chamie, Gabriel; Atukunda, Mucunguzi; Owaraganise, Asiphas; Ayieko, James; Jain, Vivek; Tamara, D. Clark; Kwarisiima, Dalsone; Maya, L. Petersen; Kamya, Moses R.; Charlebois, Edwin D.; Havlir, Diane V.; Marquez, Carina; SEARCH collaborationRates 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.Item Predictors of Retention in HIV Care among Youth (15–24) in a Universal Test-and-Treat Setting in Rural Kenya(Journal of acquired immune deficiency syndromes, 2017) Brown, Lillian B.; Ayieko, James; Mwangwa, Florence; Owaraganise, Asiphas; Kwarisiima, Dalsone; Bukusi, Elizabeth A.; Kamya, Moses R.; Petersen, Maya L.; Charlebois, Edwin D.; Havlir, Diane V.n 2013, 4 million youth age 15–24 years were living with HIV and 85% of HIV-infected youth live in sub-Saharan Africa1, where AIDS is the number-one cause of death of adolescents2. The magnitude of the HIV epidemic among youth in sub-Saharan Africa is expected to increase as demographic projections predict a “youth bulge”, increasing the population at risk for new infections, and leading to a doubling of the 15–24 year old HIV-infected cohort in sub-Saharan Africa by 20203. Retention in HIV care among this age group is essential to maximizing the benefits of antiretroviral therapy (ART), including improved quality of life, greater life expectancy, and prevention of new infections. Prior to guidelines for universal treatment, HIV-infected youth who started ART were more likely to be lost to follow-up4–6, report lower adherence4,6, and were more likely to have detectable viral loads than older age groups4,5,7. After two years of universal HIV testing and treatment in rural east Africa as part of the Sustainable East Africa Research in Community Health (SEARCH) trial, 82% of all adults with HIV in intervention communities were virally suppressed compared to only 67% of those age 15–248. These data suggest that even when high levels of viral suppression are achieved at the population level, current disparities could be exacerbated under universal treatment unless engagement in care among youth is specifically addressed. Understanding factors associated with retention in care, including any unique predictors, among this vulnerable age group will help develop additional interventions. We describe predictors of 12-month retention in HIV care among youth (15–24 years) who are linking to HIV care for the first time in rural Kenya as part of the ongoing SEARCH universal test-and-treat trial and compare these to young adults (25–29 years) and older adults (≥30 years).Item 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(AIDS care, 2022) Mwangwa, Florence; Ayieko, James; Olio, Winter; Peng, James; Kwarisiima, Dalsone; Kabami, Jane; Kapogiannis, Bill; Kamya, Moses R.; Havlir, Diane V.; Ruel, Theodore D.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.Item Understanding Demand for PrEP and Early Experiences of PrEP Use Among Young Adults in Rural Kenya and Uganda: A Qualitative Study(AIDS and Behavior, 2020) Camlin, Carol S.; Koss, Catherine A.; Owino, Lawrence; Akatukwasa, Cecilia; Bakanoma, Robert; Onyango, Anjeline; Atwine, Frederick; Ayieko, James; Kabami, Jane; Mwangwa, Florence; Atukunda, Mucunguzi; Owaraganise, Asiphas; Kwarisiima, Dalsone; Bukusi, Elizabeth A.; Kamya, Moses R.; Maya, L. Petersen; Cohen, Craig R.; Charlebois, Edwin D.; Havlir, Diane V.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.Item Uptake and Outcomes of a Novel Community-Based HIV Post-exposure Prophylaxis (PEP) Programme in Rural Kenya and Uganda(Journal of the International AIDS Society, 2021) Ayieko, James; Petersen, Maya L.; Kabami, Jane; Mwangwa, Florence; Nyabuti, Marilyn; Charlebois, Edwin D.; Bukusi, Elizabeth A.; Kamya, Moses R.; Havlir, Diane V.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. 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. 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. 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.Item Uptake, Engagement, and Adherence to Pre-Exposure Prophylaxis offered after Population HIV Testing in Rural Kenya and Uganda: 72-Week Interim Analysis of Observational Data from the SEARCH Study(The Lancet HIV, 2020) Koss, Catherine A.; Charlebois, Edwin D.; Ayieko, James; Kwarisiima, Dalsone; Kabami, Jane; Balzer, Laura B.; Atukunda, Mucunguzi; Mwangwa, Florence; Peng, James; Mwinike, Yusuf; Owaraganise, Asiphas; Olilo, Winter; Marquez, Carina; Tamara, D. Clark; Bukusi, Elizabeth A.; Maya, L. Petersen; Kamya, Moses R.; Havlir, Diane V.; for the SEARCH CollaborationOptimal strategies for pre-exposure prophylaxis (PrEP) engagement in generalised HIV epidemics are unknown. We aimed to assess PrEP uptake and engagement after population-level HIV testing and universal PrEP access to characterise gaps in the PrEP cascade in rural Kenya and Uganda. We did a 72-week interim analysis of observational data from the ongoing SEARCH (Sustainable East Africa Research in Community Health) study. Following community sensitisation and PrEP education, we did HIV testing and offered PrEP at health fairs and facilities in 16 rural communities in western Kenya, eastern Uganda, and western Uganda. We provided enhanced PrEP counselling to individuals 15 years and older who were assessed as having an elevated HIV risk on the basis of serodifferent partnership or empirical risk score, or who otherwise self-identified as being at high risk but were not in serodifferent partnerships or identified by the risk score. PrEP follow-up visits were done at facilities, homes, or community locations. We assessed PrEP uptake within 90 days of HIV testing, programme engagement (follow-up visit attendance at week 4, week 12, and every 12 weeks thereafter), refills, self-reported adherence up to 72 weeks, and concentrations of tenofovir in hair samples from individuals reporting HIV risk and adherence during follow-up, and analysed factors associated with uptake and adherence. This study is registered with ClinicalTrials.gov, NCT01864603. Between June 6, 2016, and June 23, 2017, 70 379 community residents 15 years or older who had not previously been diagnosed with HIV were tested during population-level HIV testing. Of these individuals, 69 121 tested HIV-negative, 12 935 of whom had elevated HIV risk (1353 [10%] serodifferent partnership, 6938 [54%] risk score, 4644 [36%] otherwise self-identified risk). 3489 (27%) initiated PrEP, 2865 (82%) of whom did so on the same day as HIV testing and 1733 (50%) of whom were men. PrEP uptake was lower among individuals aged 15–24 years (adjusted odds ratio 0·55, 95% CI 0·45–0·68) and mobile individuals (0·61, 0·41–0·91). At week 4, among 3466 individuals who initiated PrEP and did not withdraw or die before the first visit, 2215 (64%) were engaged in the programme, 1701 (49%) received medication refills, and 1388 (40%) self-reported adherence. At week 72, 1832 (56%) of 3274 were engaged, 1070 (33%) received a refill, and 900 (27%) self-reported adherence. Among participants reporting HIV risk at weeks 4–72, refills (89–93%) and self-reported adherence (70–76%) were high. Among sampled participants self-reporting adherence at week 24, the proportion with tenofovir concentrations in the hair reflecting at least four doses taken per week was 66%, and reflecting seven doses per week was 44%. Participants who stopped PrEP accepted HIV testing at 4274 (83%) of 5140 subsequent visits; half of these participants later restarted PrEP. 29 participants of 3489 who initiated PrEP had serious adverse events, including seven deaths. Five adverse events (all grade 3) were assessed as being possibly related to the study drug. During population-level HIV testing, inclusive risk assessment (combining serodifferent partnership, an empirical risk score, and self-identification of HIV risk) was feasible and identified individuals who could benefit from PrEP. The biggest gap in the PrEP cascade was PrEP uptake, particularly for young and mobile individuals. Participants who initiated PrEP and had perceived HIV risk during follow-up reported taking PrEP, but one-third had drug concentrations consistent with poor adherence, highlighting the need for novel approaches and long-acting formulations as PrEP roll-out expands.