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  1. Home
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Browsing by Author "Owaraganise, Asiphas"

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    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, Diane
    Antiretroviral 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.
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    Costs of Streamlined HIV Care Delivery in Rural Ugandan and Kenyan Clinics in the SEARCH Study
    (AIDS, 2018) Shade, Starley B.; Osmand, Thomas; Aine, Ronald; Mwebaza, Betty; Owaraganise, Asiphas; Mwangwa, Florence; Kwarisiima, Dalsone; Bukusi, Elizabeth A.; Kamya, Moses R.; Petersenk, Maya L.; Havlir, Diane V.; Jain, Vivek
    As antiretroviral therapy (ART) rapidly expands in sub-Saharan Africa using new efficient care models, data on costs of these approaches are lacking. We examined costs of a streamlined HIV care delivery model within a large HIV test-and-treat study in Uganda and Kenya. We calculated observed per-person-per-year (ppy) costs of streamlined care in 17 health facilities in SEARCH Study intervention communities (NCT: 01864603) via micro-costing techniques, time-and-motion studies, staff interviews, and administrative records. Cost categories included salaries, ART, viral load testing, recurring goods/services, and fixed capital/facility costs. We then modeled costs under three increasingly efficient scale-up scenarios: lowest-cost ART, centralized viral load testing, and governmental healthcare worker salaries. We assessed the relationship between community-specific ART delivery costs, retention in care, and viral suppression. Estimated streamlined HIV care delivery costs were $291/ppy. ART ($117/ppy for TDF/3TC/EFV [40%]) and viral load testing ($110/ppy for 2 tests/year [39%]) dominated costs versus salaries ($51/ppy), recurring costs ($5/ppy), and fixed costs ($7/ppy). Optimized ART scale-up with lowest-cost ART ($100/ppy), annual viral load testing ($24/ppy), and governmental healthcare salaries ($27/ppy), lowered streamlined care cost to $163/ppy. We found clinic-to-clinic heterogeneity in retention and viral suppression levels versus streamlined care delivery costs, but no correlation between cost and either retention or viral suppression. In the SEARCH Study, streamlined HIV care delivery costs were similar to or lower than prior estimates despite including viral load testing; further optimizations could substantially reduce costs further. These data can inform global strategies for financing ART expansion to achieve UNAIDS 90–90–90 targets.
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    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 Collaboration
    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. 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.
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    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, Carina
    Reducing 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.
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    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 Collaboration
    We 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.
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    HIV Incidence after Pre-exposure Prophylaxis Initiation among Women and Men at Elevated HIV Risk: A Population-Based Study in rural Kenya and Uganda
    (PLoS medicine, 2021) Kabami, Jane; Atukunda, Mucunguzi; Mwinike, Yusuf; Mwangwa, Florence; Owaraganise, Asiphas; Olilo, Winter; Tamara, D. Clark; Bukusi, Elizabeth A.; Charlebois, Edwin D.; Maya, L. Petersen; Kamya, Moses R.
    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. 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. 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.
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    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 Collaboration
    Isoniazid 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.
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    Mid-level managers’ perspectives on implementing isoniazid preventive therapy for people living with HIV in Ugandan health districts: a qualitative study
    (BioMed Central Ltd, 2024-03) Christian, Canice; Kakande, Elijah; Nahurira, Violah; Akatukwasa, Cecilia; Atwine, Fredrick; Bakanoma, Robert; Itiakorit, Harriet; Owaraganise, Asiphas; DiIeso, William; Rast, Derek; Kabami, Jane; Peretz, Jason Johnson; Shade, Starley B; Kamya, Moses R; Havlir, Diane V; Chamie, Gabriel; Camlin, Carol S
    Abstract Background Isoniazid preventive therapy (IPT) works to prevent tuberculosis (TB) among people living with HIV (PLHIV), but uptake remains low in Sub-Saharan Africa. In this analysis, we sought to identify barriers mid-level managers face in scaling IPT in Uganda and the mechanisms by which the SEARCH-IPT trial intervention influenced their abilities to increase IPT uptake. Methods The SEARCH-IPT study was a cluster randomized trial conducted from 2017-2021. The SEARCH-IPT intervention created collaborative groups of district health managers, facilitated by local HIV and TB experts, and provided leadership and management training over 3-years to increase IPT uptake in Uganda. In this qualitative study we analyzed transcripts of annual Focus Group Discussions and Key Informant Interviews, from a subset of SEARCH-IPT participants from intervention and control groups, and participant observation field notes. We conducted the analysis using inductive and deductive coding (with a priori codes and those derived from analysis) and a framework approach for data synthesis. Results When discussing factors that enabled positive outcomes, intervention managers described feeling ownership over interventions, supported by the leadership and management training they received in the SEARCH-IPT study, and the importance of collaboration between districts facilitated by the intervention. In contrast, when discussing factors that impeded their ability to make changes, intervention and control managers described external funders setting agendas, lack of collaboration in meetings that operated with more of a 'top-down' approach, inadequate supplies and staffing, and lack of motivation among frontline providers. Intervention group managers mentioned redistribution of available stock within districts as well as between districts, reflecting efforts of the SEARCH-IPT intervention to promote between-district collaboration, whereas control group managers mentioned redistribution within their districts to maximize the use of available IPT stock. Conclusions In Uganda, mid-level managers' perceptions of barriers to scaling IPT included limited power to set agendas and control over funding, inadequate resources, lack of motivation of frontline providers, and lack of political prioritization. We found that the SEARCH-IPT intervention supported managers to design and implement strategies to improve IPT uptake and collaborate between districts. This may have contributed to the overall intervention effect in increasing the uptake of IPT among PLHIV compared to standard practice. Trial registration ClinicalTrials.gov, NCT03315962, Registered 20 October 2017. Keywords: TB preventive therapy, Mid-level managers, Health systems
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    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 collaboration
    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.
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    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).
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    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.
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    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 Collaboration
    Optimal 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.

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