Enhanced Oral Pre-exposure Prophylaxis (PrEP) Implementation for Ugandan Fisherfolk: Pilot Intervention Outcomes.

Mobile populations such as fisherfolk show high HIV incidence and prevalence. We pilot-tested implementation strategies to enhance pre-exposure prophylaxis (PrEP) uptake and adherence in the context of healthcare outreach events in two mainland fisherfolk communities on Lake Victoria, Uganda from September 2021 to February 2022. The implementation strategies included PrEP adherence supporters (selected from PrEP users' social networks), community workshops (to address misconceptions and stigma, and empower PrEP advocacy), and check-in calls (including refill reminders). PrEP medical records data were collected from 6-months pre-intervention to 6-months post-intervention. Qualitative interviews with 20 PrEP users (10 who continued, 10 who discontinued), 9 adherence supporters, and 7 key partners (providers, community leaders) explored acceptability. Percentages of PrEP initiators (of those eligible) were significantly higher during the intervention (96.5%) than 6-months before the intervention (84.5%), p < 0.0001; percentages of PrEP users who persisted (i.e., possessed a refill) 6-months post-initiation (47.9% vs. 6.7%) and had at least 80% PrEP coverage (based on their medication possession ratio) from the initiation date to 6-months later (35.9% vs. 0%) were higher during versus pre-intervention, p < 0.0001. A comparison fisherfolk community with better healthcare access had lower uptake (78.3%; p < 0.0001) and persistence at 6-months (34.0%; p < 0.001), but higher coverage during the intervention period (70.4%; p < 0.0001). Qualitative data suggested the strategies promoted PrEP use through reduced stigma and misconceptions. The intervention bundle cost was $223.95, $172.98, and $94.66 for each additional person for PrEP initiation, persistence, and coverage, respectively. Enhanced community-based PrEP implementation that fosters a supportive community environment can improve PrEP use in mobile populations without easy access to healthcare. (NCT05084716).

Behavioral Modeling and its Association with PrEP and ART Use in Ugandan HIV-Serodifferent Couples.

Integrating Pre-Exposure Prophylaxis (PrEP) delivery into Antiretroviral Therapy (ART) programs bridges the Human Immunodeficiency Virus (HIV) prevention gap for HIV-serodifferent couples prior to the partner living with HIV achieving viral suppression. Behavioral modeling is one mechanism that could explain health-related behavior among couples, including those using antiretroviral medications, but few tools exist to measure the extent to which behavior is modeled. Using a longitudinal observational design nested within a cluster randomized trial, this study examined the factor structure and assessed the internal consistency of a novel 24-item, four-point Likert-type scale to measure behavioral modeling and the association of behavioral modeling with medication-taking behaviors among heterosexual, cis-gender HIV-serodifferent couples. In 149 couples enrolled for research, a five-factor model provided the best statistical and conceptual fit, including attention to partner behavior, collective action, role modeling, motivation, and relationship quality. Behavioral modeling was associated with medication-taking behaviors among members of serodifferent couples. Partner modeling of ART/PrEP taking could be an important target for assessment and intervention in HIV prevention programs for HIV serodifferent couples.

A prospective cohort study of outcomes for isoniazid prevention therapy: a nested study from a national QI collaborative in Uganda.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection constitute a deadly infectious disease synergy disease and major public health problem throughout the world. The risk of developing active TB in people living with HIV (PLHIV) is 21 times higher than the rest of the world population. The overlap of latent TB infection and HIV infection has resulted in marked increases in TB incidence in countries with dual epidemics. Although antiretroviral therapy (ART) is the single most significant way to reduce incident TB in PLHIV, besides early ART initiation, isoniazid preventive therapy (IPT) is the key intervention to prevent TB among PLHIV. This prospective cohort and longitudinal study aimed to document; retention, adherence, development of active TB disease, possible adverse drug reactions and completion among patients initiated on IPT in Jan 2019. METHODS: This was both a prospective cohort and longitudinal study nested within a national quality improvement collaborative in which multiple quality improvement teams tested changes in care delivery to improve the delivery of IPT. The prospective cohort were HIV patients without TB disease initiated on a dosage of Isoniazid 300 mg/day for adults and 150 mg/day for children for a period of 6 months. Association statistics were used to describe patient characteristics and outcomes. Variables with p-value < 0.05 were used to determine linear by linear associations between patient characteristics assumed to influence both primary and secondary outcomes. Variables with a p-value < 0.05 were included in the logistical regression model. The final model included those factors that retained statistical significance. The odds ratios (OR) and adjusted OR (AOR) along with its 95% confidence interval were used to determine the power of relationship in determining the outcomes of interest. The model was tested for fitness using goodness-of-fit Hosmer-Lemeshow tests. RESULTS: The completion of IPT was at 89%. A significant proportion of patients adhered to treatment (89%) and kept their appointment schedules-retention (89%). All patients (100%) received IPT at each appointment visit. Only 4% of patients experienced side effects of isoniazid (INH) but none of them developed active TB at the end of the 6 month INH dose. Multivariate logistic regression analysis of covariates of IPT completion revealed a strong and statistical association between IPT completion and age, gender, retention and side effects of INH. Our multivariate model found that children below 15 years were less likely to complete INH than patients ≥ 15 years (AOR = 0.416, p = 0.230, df = 1). Female patients were 2 times more likely to complete INH dose than male patients (AOR = 1.598, p = 0.018). Patients who kept all their appointment schedules were 10 times more likely to complete IPT than those who missed one or more schedules (AOR = 10.726, p = 0.000, df = 1). We also found that patients who did not report any side effects associated with INH were 2 times more likely to complete INH (AOR = 1.958, p = 0.016, df = 1) than patients who reported one or more side effects. CONCLUSION: Treatment completion is the end-point of the IPT initiation strategy in Uganda. With a completion rate of 89%, our results seem re-assuring and suggest that improvement collaborative is an effective approach to achieving results through combined efforts. The high rates of completion are encouraging indicators of progress in the implementation of collaborative activities in the study setting. However, such collaboratives would require periodic evaluation to prevent possible relapses in progress attained.

Applying a Three-Tier Approach to Address Gaps in Oral Pre-Exposure Prophylaxis Uptake and Continuity in Uganda: A Mixed Methods Approach.

BACKGROUND: We describe a 3-tier approach involving a gap analysis, root cause analysis, and pre-exposure prophylaxis (PrEP) collaborative to understand the gap and identify and address the main barriers to oral PrEP uptake and continuity in Uganda. METHODS: We used a mixed methods design with retrospective, cross-sectional, and prospective components. The gap analysis involved descriptive analysis of PrEP uptake and continuity. The RCA identified the main barriers to initiation and continuity on PrEP among 1,334 clients who declined to start PrEP and 1,266 who missed their appointment but were at risk. The PrEP collaborative tested changes mapped onto specific barriers to optimize the PrEP clinical service delivery. A trend analysis of routinely collected data of the PrEP cascade determined significant shifts and trends in PrEP uptake and continuity. RESULTS: Only 60% of the high-risk population eligible for PrEP were enrolled, while fewer than 30% of the cumulative number of PrEP users were refilled each quarter. Uncertainty and fear of side effects, perceptions about the harmfulness of the medication, perceived inability to adhere to PrEP, and stigma were the main reasons why clients rejected PrEP. Lack of access to the facility, side effects, pill burden, stigma, perceived low-risk exposure to HIV, and preference of staying at work as opposed to picking up refills affected continuity on PrEP. The collaborative registered statistically significant shifts in PrEP enrollment from 64% to 89% and continuity from 51% to 78% between July 21 and November 22 following the collaborative intervention. CONCLUSIONS: We recommend using a 3-tier approach for other similar implementation contexts to strengthen PrEP programming, given the marked statistical shift in PrEP uptake and continuity. This begins with understanding the gap and barriers to use among clients, followed by mapping interventions to specific barriers through a quality improvement collaborative.

"Take services to the people": strategies to optimize uptake of PrEP and harm reduction services among people who inject drugs in Uganda.

BACKGROUND: People who inject drugs (PWID) are at increased risk of HIV acquisition and often encounter barriers to accessing healthcare services. Uganda has high HIV prevalence among PWID and lacks integrated pre-exposure prophylaxis (PrEP) and harm reduction services. Understanding PWID experiences accessing and using harm reduction services and PrEP will inform strategies to optimize integration that align with PWID needs and priorities. METHODS: Between May 2021 and March 2023, we conducted semi-structured interviews with PWID in Kampala, Uganda. We recruited participants with and without previous experience accessing harm reduction services and/or PrEP using purposive and snowball sampling. Interviews were audio recorded, translated, and transcribed. We used thematic analysis to characterize motivations for uptake of harm reduction and HIV prevention services, and strategies to optimize delivery of needle and syringe programs (NSP), medications for opioid use disorder (MOUD), and PrEP. RESULTS: We conducted interviews with 41 PWID. Most participants were relatively aware of their personal HIV risk and accurately identified situations that increased risk, including sharing needles and engaging in transactional sex. Despite risk awareness, participants described engaging in known HIV risk behaviors to satisfy immediate drug use needs. All reported knowledge of harm reduction services, especially distribution of sterile needles and syringes, and many reported having experience with MOUD. Participants who had accessed MOUD followed two primary trajectories; limited resources and relationships with other PWID caused them to discontinue treatment while desire to regain something they believed was lost to their drug use motivated them to continue. Overall, PrEP knowledge among participants was limited and few reported ever taking PrEP. However, participants supported integrating PrEP into harm reduction service delivery and advocated for changes in how these services are accessed. Stigma experienced in healthcare facilities and challenges acquiring money for transportation presented barriers to accessing current facility-based harm reduction and HIV prevention services. CONCLUSIONS: Meeting the HIV prevention needs of PWID in Uganda will require lowering barriers to access, including integrated delivery of PrEP and harm reduction services and bringing services directly to communities. Additional training in providing patient-centered care for healthcare providers may improve uptake of facility-based services.

Recommendations for Improving Oral Pre-exposure Prophylaxis Implementation and Social Marketing in Ugandan Fisherfolk Communities: A Qualitative Exploration.

Background: HIV is hyperendemic among fisherfolk in Sub-Saharan Africa, especially around Lake Victoria, Uganda. Purpose/Research Design: We conducted cross-sectional semi-structured interviews about oral pre-exposure prophylaxis (PrEP) implementation with 35 Ugandan fisherfolk (15 women, 20 men) and 10 key stakeholders (healthcare providers, policymakers, community leaders). We used a directed content analysis approach based on implementation science and social marketing frameworks. Results: Participants showed high acceptability for PrEP. Anticipated barriers among fisherfolk included stigma (due to similar medications/packaging as HIV treatment); misconceptions; mobility, competing needs, poverty, and partner conflict. Anticipated provider barriers included insufficient staffing and travel support. Recommendations included: change PrEP packaging; integrate PrEP with other services; decrease PrEP refill frequency; give transportation resources to providers; train more healthcare workers to provide PrEP to fisherfolk; and use positively framed messages to promote PrEP. Conclusions: Results can inform policymakers and healthcare organizations on how to overcome barriers to PrEP scale-up in most at-risk populations with poor healthcare access.

Intimate Partner Violence and Adherence to PrEP and ART Among Ugandan HIV Serodifferent Couples.

BACKGROUND: Intimate partner violence (IPV) is associated with increased risk of HIV acquisition and reduced engagement in HIV care. There is limited understanding of the ways in which IPV exposure and other maladaptive relationship dynamics may influence adherence to antiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP) for individuals in committed, HIV serodifferent partnerships. METHODS: We used binomial generalized linear mixed-effect regression models to evaluate the association between IPV exposure and ART/PrEP adherence among members of serodifferent couples in Uganda. Secondarily, we assessed the association between relationship powerlessness and ART/PrEP adherence. RESULTS: We enrolled and followed both partners in 149 heterosexual serodifferent couples. The partner living with HIV was female in 64% of couples. IPV exposure was associated with low ART adherence (15% vs. 5% in quarters with no IPV, odds ratio: 4.78, 95% confidence interval: 1.48 to 15.42), but not low PrEP adherence (33% vs. 36%, P = 0.69). Among HIV-negative individuals, those reporting moderate relationship powerlessness were less likely to have poor PrEP adherence compared with those with low relationship powerlessness (20% vs. 30%, odds ratio: 0.57, 95% confidence interval: 0.36 to 0.90). We observed no association between relationship powerlessness and ART adherence. CONCLUSIONS: We found that IPV exposure was associated with low adherence to ART and that relationship powerlessness was associated with good adherence to PrEP. These findings contribute to the evidence base outlining the influence of IPV and relationship power on ART/PrEP adherence for individuals in HIV serodifferent unions.

Clients in Uganda accessing preferred differentiated antiretroviral therapy models achieve higher viral suppression and are less likely to miss appointments: a cross-sectional analysis.

INTRODUCTION: The Uganda Ministry of Health recommends facility- and community-based differentiated antiretroviral therapy (DART) models to support person-centred care for eligible clients receiving antiretroviral therapy (ART). Healthcare workers assess client eligibility for one of six DART models upon initial enrolment; however, client circumstances evolve, and their preferences are not routinely adjusted. We developed a tool to understand the proportion of clients accessing preferred DART models and compared the outcomes of clients accessing preferred DART models to the outcomes of clients not receiving preferred DART models. METHODS: We conducted a cross-sectional study. A sample of 6376 clients was selected from 113 referrals, general hospitals and health centres purposely selected from 74 districts. Clients receiving ART accessing care from the sampled sites were eligible for inclusion. Healthcare workers interviewed clients (caretakers of clients under 18), over a 2-week period between January and February 2022 using a client preference tool to elicit whether clients were receiving DART services through their preferred model. Treatment outcomes of viral load test, viral load suppression and missed appointment date were extracted from clients' medical files before or immediately after the interview and de-identified. The descriptive analysis determined the interaction between client preferences and predefined treatment outcomes by comparing outcomes of clients whose care aligned with their preferences to outcomes of clients whose care misaligned with their preferences. RESULTS: Of 25% (1573/6376) of clients not accessing their preferred DART model, 56% were on facility-based individual management and 35% preferred fast-track drug refills model. Viral load coverage was 87% for clients accessing preferred DART models compared to 68% among clients not accessing their preferred model. Viral load suppression was higher among clients who accessed the preferred DART model (85%) compared to (68%) clients who did not access their preferred DART model. Missed appointments were lower at 29% for clients who accessed preferred DART models compared to 40% among clients not enrolled in the DART model of their choice. CONCLUSIONS: Clients who accessed their preferred DART model have better clinical outcomes. Preferences should be integrated throughout health systems, improvement interventions, policies and research efforts to ensure client-centred care and client autonomy.

PrEP uptake and HIV viral suppression when PrEP is integrated into Ugandan ART clinics for HIV-negative members of HIV-serodifferent couples: A stepped wedge cluster randomized trial.

Background: Global scale-up of HIV pre-exposure prophylaxis (PrEP) includes services to HIV-negative people in partnerships with people living with HIV (serodifferent couples). Data are needed on HIV outcomes, including uptake and adherence to PrEP and antiretroviral treatment (ART), to describe the impact of integrating PrEP into an existing HIV program. Methods: Using a stepped-wedge cluster randomized trial design, we launched PrEP delivery for HIV-negative members of serodifferent couples in Uganda by integrating PrEP into existing ART programs for people living with HIV. The program provided PrEP training for ART providers, ongoing technical assistance, and a provisional supply chain mechanism for PrEP medication. Primary data on PrEP initiation, PrEP refills, ART initiation, and HIV viremia at 6 months (measured at 42-270 days) were collected through data abstraction of medical records from HIV-serodifferent couples sequentially enrolling at the ART clinics. Modified Poisson regression models, controlling for time and cluster, compared viral suppression (<1000 copies/ml) before and after launch of the PrEP program. This trial was registered at ClinicalTrials.gov, NCT03586128. Findings: From June 1, 2018-December 15, 2020, 1,381 HIV-serodifferent couples were enrolled across 12 ART clinics in Kampala and Wakiso, Uganda, including 730 enrolled before and 651 after the launch of PrEP delivery. During the baseline period, 99.4% of partners living with HIV initiated ART and 85.0% were virally suppressed at 6 months. Among HIV-negative partners enrolled after PrEP launched, 81.0% (527/651) initiated PrEP within 90 days of enrolling; among these 527, 11.2% sought a refill 6 months later. In our powered intent-to-treat analysis, 82.1% and 76.7% of partners living with HIV were virally suppressed, respectively, which was not a statistically significant difference (RR=0.94, 95% CI: 0.82-1.07) and was stable across sensitivity analyses. Interpretation: Integration of PrEP into ART clinics reached a high proportion of people in HIV-serodifferent relationships and did not improve the already high frequency of HIV viral suppression among partners living with HIV. Funding: National Institute of Mental Health (R01MH110296).