Browsing by Author "Atukunda, Mucunguzi"

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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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    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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    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.