Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.

BACKGROUND: There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women. METHODS: We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAF by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF. RESULTS: Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P = 0.21), and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions. CONCLUSIONS: No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 1 ClinicalTrials.gov number, NCT04994509.).

Comparison of 3 optimized delivery strategies for completion of isoniazid-rifapentine (3HP) for tuberculosis prevention among people living with HIV in Uganda: A single-center randomized trial.

BACKGROUND: Expanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies. METHODS AND FINDINGS: In a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher's exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p < 0.001), SAT (0.92; 97.5% CI [0.89, 0.94] p < 0.001), and Choice (0.93; 97.5% CI [0.91, 0.96] p < 0.001) arms. There was no difference in acceptance and completion between any 2 arms overall or in prespecified subgroup analyses based on sex, age, time on antiretroviral therapy, and history of prior treatment for TB or TB infection. Only 14 (0.8%) participants experienced an adverse event prompting discontinuation of 3HP. The main limitation of the study is that it was conducted in a single center. Multicenter studies are now needed to confirm the feasibility and generalizability of the facilitated 3HP delivery strategies in other settings. CONCLUSIONS: Short-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers. TRIAL REGISTRATION: ClinicalTrials.gov NCT03934931.

Effectiveness of intensive adherence counselling in achieving an undetectable viral load among people on antiretroviral therapy with low-level viraemia in Uganda.

INTRODUCTION: Uganda was using a threshold of 1000 copies/mL to determine viral non-suppression for antiretroviral therapy monitoring among people living with HIV, prior to this study. It was not clear whether people living with HIV with low-level viraemia (LLV, ≥50 to <1000 copies/mL) would benefit from intensive adherence counselling (IAC). The purpose of this study was to determine the effectiveness of IAC among people living with HIV, receiving antiretroviral therapy, and with LLV in Uganda, to guide key policy decisions in HIV care, including the review of the viral load (VL) testing algorithm. METHODS: This cluster-randomized clinical trial comprised adults from eight HIV clinics who were living with HIV, receiving ART, and had recent VL results indicating LLV (tested from July 2022 to October 2022). Participants in the intervention arm clinics received three once-monthly sessions of IAC, and those in the comparison non-intervention arm clinics received the standard of care. At the end of the study, all participants were re-tested for VL to determine the proportions of those who then had an undetectable VL (<50 copies/mL). We assessed the statistical association between cross-tabulated variables using Fisher's exact test and then modified Poisson regression. RESULTS: A total of 136 participants were enrolled into the study at eight HIV clinics. All 68 participants in the intervention arm completed all IAC sessions. Only one participant in the non-intervention arm was lost to follow-up. The average follow-up time was 3.7 months (standard deviation [SD] 0.2) and 3.5 months (SD 0.1) in the intervention and non-intervention arms, respectively. In total, 59 (43.7%) of 135 people living with HIV achieved an undetectable VL during the study follow-up period. The effect of IAC on attaining an undetectable VL among people with LLV was nearly twice as high in the intervention arm (57.4%) than in the non-intervention arm (29.9%): adjusted risk ratio 1.9 (95% confidence interval 1.0-3.5), p = 0.037. CONCLUSION: IAC doubled the likelihood of an undetectable VL among people living with HIV with LLV. Therefore, IAC has been instituted as an intervention to manage people living with HIV with LLV in Uganda, and this should also be adopted in other Sub-Saharan African countries with similar settings. GOV IDENTIFIER: NCT05514418.

A randomized control trial to compare mortality in recipients of leucoreduced and non-leucoreduced whole blood transfusion in patients with cancer in Uganda.

BACKGROUND: Mortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting. METHODS: An open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality. RESULTS: There were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1-3) unit and 2 (IQR, 1-3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1-10) and was 6.2% (95% CI, 3.2-12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86-0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00-0.31, p < 0.01) were associated with reduced 30-day mortality. CONCLUSIONS: The study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed. TRIAL REGISTRATION: Pan African Clinical Trial Registry, https://pactr.samrc.ac.za/ (PACTR202302787440132). Registered on 06/02/2023.

Strengthening anthrax outbreak response and preparedness: simulation and stakeholder education in Namisindwa district, Uganda.

BACKGROUND: Anthrax is a zoonotic disease caused by Bacillus anthracis that poses a significant threat to both human health and livestock. Effective preparedness and response to anthrax outbreak at the district level is essential to mitigate the devastating impact of the disease to humans and animals. The current diseaae surveillance in animals and humans uses two different infrastructure systems with online platform supported by established diagnostic facilities. The differences in surveillance systems affect timely outbreak response especially for zoonotic diseases like anthrax. We therefore aimed to assess the feasibility of implementing a simulation exercise for a potential anthrax outbreak in a local government setting and to raise the suspicion index of different district stakeholders for a potential anthrax outbreak in Namisindwa District, Uganda. METHODS: We conducted a field-based simulation exercise and a health education intervention using quantitative data collection methods. The study participants mainly members of the District Taskforce (DTF) were purposively selected given their role(s) in disease surveillance and response at the sub-national level. We combined 26 variables (all dichotomized) assessing knowledge on anthrax and knowledge on appropriate outbreak response measures into an additive composite index. We then dichotomized overall score based on the 80% blooms cutoff i.e. we considered those scoring at least 80% to have high knowledge, otherwise low. We then assessed the factors associated with knowledge using binary logistic regression with time as a proxy for the intervention effect. Odds ratios (ORs) and 95% Confidence intervals (95%CI) have been reported. RESULTS: The overall district readiness score was 35.0% (24/69) and was deficient in the following domains: coordination and resource mobilization (5/16), surveillance (5/11), laboratory capacity (3/10), case management (4/7), risk communications (4/12), and control measures (4/13). The overall community readiness score was 7 out of 32 (22.0%). We noted poor scores of readiness in all domains except for case management (2/2). The knowledge training did not have an effect on the overall readiness score, but improved specific domains such as control measures. Instead tertiary education was the only independent predictor of higher knowledge on anthrax and how to respond to it (OR = 1.57, 95% CI = 1.07-2.31). Training did not have a significant association with overall knowledge improvement but had an effect on several individual knowledge aspects. CONCLUSION: We found that the district's preparedness to respond to a potential anthrax outbreak was inadequate, especially in coordination and mobilisation, surveillance, case management, risk communication and control measures. The health education training intervention showed increased knowledge levels compared to the pre-test and post-test an indicator that the health education sessions could increase the index of suspicion. The low preparedness underscores the urgency to strengthen anthrax preparedness in the district and could have implications for other districts. We deduce that trainings of a similar nature conducted regularly and extensively would have better effects. This study's insights are valuable for improving anthrax readiness and safeguarding public and animal health in similar settings.

Prevalence and factors associated with reported adverse-events among patients on multi-drug-resistant tuberculosis treatment in two referral hospitals in Uganda.

BACKGROUND: Multi-drug-resistant tuberculosis (MDR-TB) treatment involves toxic drugs that cause adverse events (AEs), which are life-threatening and may lead to death if not well managed. In Uganda, the prevalence of MDR-TB is increasingly high, and about 95% of the patients are on treatment. However, little is known about the prevalence of AEs among patients on MDR-TB medicines. We therefore estimated the prevalence of reported adverse events (AEs) of MDR-TB drugs and factors associated with AEs in two health facilities in Uganda. METHODS: A retrospective cohort study of MDR-TB was conducted among patients enrolled at Mulago National Referral and Mbarara Regional Referral hospitals in Uganda. Medical records of MDR-TB patients enrolled between January 2015 and December 2020 were reviewed. Data on AEs, which were defined as irritative reactions to MDR-TB drugs, were extracted and analyzed. To describe reported AEs, descriptive statistics were computed. A modified Poisson regression analysis was used to determine factors associated with reported AEs. RESULTS: Overall, 369 (43.1%) of 856 patients had AEs, and 145 (17%) of 856 had more than one. Joint pain (244/369, or 66%), hearing loss (75/369, or 20%), and vomiting (58/369, or 16%) were the most frequently reported effects. Patients started on the 24-month regimen (adj. PR = 1.4, 95%; 1.07, 1.76) and individualized regimens (adj. PR = 1.5, 95%; 1.11, 1.93) were more likely to suffer from AEs. Lack of transport for clinical monitoring (adj. PR = 1.9, 95%; 1.21, 3.11); alcohol consumption (adj. PR = 1.2, 95%; 1.05, 1.43); and receipt of directly observed therapy from peripheral health facilities (adj. PR = 1.6, 95%; 1.10, 2.41) were significantly associated with experiencing AEs. However, patients who received food supplies (adj. PR = 0.61, 95%; 0.51, 0.71) were less likely to suffer from AEs. CONCLUSION: The frequency of adverse events reported by MDR-TB patients is considerably high, with joint pain being the most common. Interventions such as the provision of food supplies, transportation, and consistent counseling on alcohol consumption to patients at initiation treatment facilities may contribute to a reduction in the rate of occurrence of AEs.

Evaluating the effectiveness of Uganda's Supranational TB Reference Laboratory quality management system training program.

BACKGROUND: Achieving the targeted organizational goals through effective training can increase employee satisfaction. Since 2015, the Supranational Reference Laboratory Uganda (SRL Uganda) has trained National Tuberculosis Reference Laboratories (NTRLs) from 21 countries in a variety of areas that cover both technical and programmatic aspects pertinent to TB laboratories. The Laboratory Quality Management System (LQMS) under SRL coordinates actions intended to ensure sustained quality of the laboratory services offered by the National TB Reference Laboratories. In order for laboratory results to be helpful in a clinical or public health setting, they must be accurate, reliable, and timely. The LQMS course aims to provide learners with knowledge on how to attain and maintain this quality. Prior to this study, there was hardly any data available on the effectiveness of LQMS trainings provided by SRL Uganda; using Kirkpatrick model, which is popular among researchers for evaluating the efficacy of the training program, this paper seeks to establish the effectiveness of the LQMS training offered by the SRL Uganda. METHOD: We evaluated the effectiveness of LQMS training within the Uganda's SRL network for courses offered during the period 2017 and 2021 for participants from the Southern and East African sub-Saharan region. RESULTS: In 2017 and 2021, respectively, test results from 10/17 and 9/17 showed overall post-test scores above 80%. Of the 18 labs evaluated, 14 showed improvement; of these, 7 labs were from the Eastern region and the other 7 were from Southern Africa; one facility in this region also maintained its accreditation. In the post-evaluation assessment, attendees of the LQMS course gave feedback of strongly agree and agree variety. CONCLUSION: More SRL Uganda network laboratories in the regions achieved a 5-star SLIPTA level rating and among these, 5 NTRLs got ISO 15189:2012 accredited by the end of 2021, while one maintained its accreditation status. This proves that the Laboratory Quality Management System training program was an effective tool in improving the quality of laboratory services, work practices, and processes.

A user-centred implementation strategy for tuberculosis contact investigation in Uganda: protocol for a stepped-wedge, cluster-randomised trial.

BACKGROUND: Tuberculosis(TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented. METHODS: We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including (1) a TB-education booklet, (2) a contact-identification algorithm, (3) an instructional sputum-collection video, and (4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including (1) collaborative improvement meetings, (2) regular audit-and-feedback reports, and (3) a digital group-chat application designed to develop a community of practice. Sites will cross-over from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB(#554), the Uganda National Council for Science and Technology(#HS1720ES), and the Yale Institutional Review Board(#2000023199) approved the study and waived informed consent for the main trial implementation-effectiveness outcomes. We will submit results for publication in peer-reviewed journals and disseminate findings to local policymakers and representatives of affected communities. DISCUSSION: This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden settings using contact investigation. It will also help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustaining evidence-based interventions in low-and-middle-income countries. TRIAL REGISTRATION: The trial was registered(ClinicalTrials.gov Identifier NCT05640648) on 16 November 2022, after the trial launch on 7 March 2022.

Excess Risk of Tuberculosis Infection Among Extra-household Contacts of Tuberculosis Cases in an African City.

BACKGROUND: Although households of tuberculosis (TB) cases represent a setting for intense transmission of Mycobacterium tuberculosis, household exposure accounts for <20% of transmission within a community. The aim of this study was to estimate excess risk of M. tuberculosis infection among household and extra-household contacts of index cases. METHODS: We performed a cross-sectional study in Kampala, Uganda, to delineate social networks of TB cases and matched controls without TB. We estimated the age-stratified prevalence difference of TB infection between case and control networks, partitioned as household and extra-household contacts. RESULTS: We enrolled 123 index cases, 124 index controls, and 2415 first-degree network contacts. The prevalence of infection was highest among household contacts of cases (61.5%), lowest among household contacts of controls (25.2%), and intermediary among extra-household TB contacts (44.9%) and extra-household control contacts (41.2%). The age-adjusted prevalence difference between extra-household contacts of cases and their controls was 5.4%. The prevalence of infection was similar among the majority of extra-household case contacts and corresponding controls (47%). CONCLUSIONS: Most first-degree social network members of TB cases do not have adequate contact with the index case to experience additional risk for infection, but appear instead to acquire infection through unrecognized exposures with infectious cases in the community.

Digital adherence technology for tuberculosis treatment supervision: A stepped-wedge cluster-randomized trial in Uganda.

BACKGROUND: Adherence to and completion of tuberculosis (TB) treatment remain problematic in many high-burden countries. 99DOTS is a low-cost digital adherence technology that could increase TB treatment completion. METHODS AND FINDINGS: We conducted a pragmatic stepped-wedge cluster-randomized trial including all adults treated for drug-susceptible pulmonary TB at 18 health facilities across Uganda over 8 months (1 December 2018-31 July 2019). Facilities were randomized to switch from routine (control period) to 99DOTS-based (intervention period) TB treatment supervision in consecutive months. Patients were allocated to the control or intervention period based on which facility they attended and their treatment start date. Health facility staff and patients were not blinded to the intervention. The primary outcome was TB treatment completion. Due to the pragmatic nature of the trial, the primary analysis was done according to intention-to-treat (ITT) and per protocol (PP) principles. This trial is registered with the Pan African Clinical Trials Registry (PACTR201808609844917). Of 1,913 eligible patients at the 18 health facilities (1,022 and 891 during the control and intervention periods, respectively), 38.0% were women, mean (SD) age was 39.4 (14.4) years, 46.8% were HIV-infected, and most (91.4%) had newly diagnosed TB. In total, 463 (52.0%) patients were enrolled on 99DOTS during the intervention period. In the ITT analysis, the odds of treatment success were similar in the intervention and control periods (adjusted odds ratio [aOR] 1.04, 95% CI 0.68-1.58, p = 0.87). The odds of treatment success did not increase in the intervention period for either men (aOR 1.24, 95% CI 0.73-2.10) or women (aOR 0.67, 95% CI 0.35-1.29), or for either patients with HIV infection (aOR 1.51, 95% CI 0.81-2.85) or without HIV infection (aOR 0.78, 95% CI 0.46-1.32). In the PP analysis, the 99DOTS-based intervention increased the odds of treatment success (aOR 2.89, 95% CI 1.57-5.33, p = 0.001). The odds of completing the intensive phase of treatment and the odds of not being lost to follow-up were similarly improved in PP but not ITT analyses. Study limitations include the likelihood of selection bias in the PP analysis, inability to verify medication dosing in either arm, and incomplete implementation of some components of the intervention. CONCLUSIONS: 99DOTS-based treatment supervision did not improve treatment outcomes in the overall study population. However, similar treatment outcomes were achieved during the control and intervention periods, and those patients enrolled on 99DOTS achieved high treatment completion. 99DOTS-based treatment supervision could be a viable alternative to directly observed therapy for a substantial proportion of patients with TB. TRIAL REGISTRATION: Pan-African Clinical Trials Registry (PACTR201808609844917).

Completion of isoniazid-rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness-implementation randomized trial.

BACKGROUND: Scaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid-rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization's (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa. METHODS AND FINDINGS: The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness-implementation randomized trial comparing 3 optimized strategies for delivering 3HP-facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid-to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (≥11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes. CONCLUSIONS: 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03934931.

Heme oxygenase-1 and neopterin plasma/serum levels and their role in diagnosing active and latent TB among HIV/TB co-infected patients: a cross sectional study.

BACKGROUND: Tuberculosis (TB) diagnosis in the context of HIV co-infection remains challenging. Heme oxygenase 1 (HO-1) and neopterin have been validated as potential biomarkers for TB diagnosis. Latent TB infection (LTBI) is diagnosed using tuberculin skin test (TST) and interferon gamma release assays (T-Spot and QuantiFERON TB gold tests, respectively). However, these tests have shown challenges and yet diagnosing LTBI is important for the overall control of TB. This study was conducted to determine the levels of H0-1 and neopterin, and their role in the diagnosis of TB among individuals enrolled in the Community Health and Social Network of Tuberculosis (COHSONET) study and the Kampala TB Drug Resistance Survey (KDRS). METHODS: This was a nested cross-sectional study. Plasma and serum samples collected from 140 patients at Mulago National Referral Hospital, Kampala Uganda were used. M.tb culture was performed on sputum to confirm active TB(ATB) and QuantiFERON TB gold test to confirm latent TB infection (LTBI). ELISAs were performed to determine the levels of HO-1 and neopterin. Data analysis was done using t-test and Receiver Operating Characteristic curves to determine the diagnostic accuracy. RESULTS: HO-1 levels among active tuberculosis (ATB)/HIV-infected patients and LTBI/HIV-infected patients were 10.7 ng/ml (IQR: 7.3-12.7 ng/ml) and 7.5 ng/ml (IQR: 5.4-14.1 ng/ml) respectively. Neopterin levels among ATB/HIV-positive patients and LTBI/HIV-positive patients were 11.7 ng/ml (IQR: 5.2.4 ng/ml) and 8.8 ng/ml (IQR: 2.4-19.8 ng/ml), respectively. HO-1 showed a sensitivity of 58.57% and a specificity of 67.14% with area under the curve (AUC) of 0.57 when used to discriminate between ATB and LTB. Neopterin showed an AUC of 0.62 with a sensitivity of 57.14% and a specificity of 60.0% when used to distinguish ATB from LTB. CONCLUSION: There was no in significant difference in HO-1 concentration levels of ATB individuals compared to LTB individuals. There was a significant difference in neopterin concentrations levels of ATB individuals compared to latently infected individuals. Findings from this study, show that HO-1 and neopterin have poor ability to distinguish between ATB and LTB.

Association between tuberculosis in men and social network structure in Kampala, Uganda.

BACKGROUND: Globally, tuberculosis disease (TB) is more common among males than females. Recent research proposes that differences in social mixing by sex could alter infection patterns in TB. We examine evidence for two mechanisms by which social-mixing could increase men's contact rates with TB cases. First, men could be positioned in social networks such that they contact more people or social groups. Second, preferential mixing by sex could prime men to have more exposure to TB cases. METHODS: We compared the networks of male and female TB cases and healthy matched controls living in Kampala, Uganda. Specifically, we estimated their positions in social networks (network distance to TB cases, degree, betweenness, and closeness) and assortativity patterns (mixing with adult men, women, and children inside and outside the household). RESULTS: The observed network consisted of 11,840 individuals. There were few differences in estimates of node position by sex. We found distinct mixing patterns by sex and TB disease status including that TB cases have proportionally more adult male contacts and fewer contacts with children. CONCLUSIONS: This analysis used a network approach to study how social mixing patterns are associated with TB disease. Understanding these mechanisms may have implications for designing targeted intervention strategies in high-burden populations.

Drivers and barriers to workplace-based HIV self-testing among high-risk men in Uganda: a qualitative study.

BACKGROUND: Men in Sub-Saharan Africa are less engaged than women in accessing HIV testing and treatment and, consequently, experience higher HIV-related mortality. Reaching men with HIV testing services is challenging, thus, increasing the need for innovative ways to engage men with low access and those at higher risk. In this study, we explore men's perceptions of drivers and barriers of workplace-based HIV self-testing in Uganda. METHODS: An exploratory study involving men working in private security companies employing more than 50 men in two districts, in central and western Uganda. Focus group discussions and key informant interviews were conducted. Data were analyzed using inductive content analysis. RESULTS: Forty-eight (48) men from eight private security companies participated in 5 focus group discussions and 17 key informant interviews. Of the 48 men, 14(29.2%) were ages 26-35 years. The majority 31(64.6%) were security guards. The drivers reported for workplace-based HIV self-testing included convenience, autonomy, positive influence from work colleagues, the need for alternative access for HIV testing services, incentives, and involvement of employers. The barriers reported were the prohibitive cost of HIV tests, stigma, lack of testing support, the fear of discrimination and isolation, and concerns around decreased work productivity in the event of a reactive self-test. CONCLUSIONS: We recommend the involvement of employers in workplace-based HIV self-testing to encourage participation by employees. There is need for HIV self-testing support both during and after the testing process. Both employers and employees recommend the use of non-monetary incentives, and regular training about HIV self-testing to increase the uptake and acceptability of HIV testing services at the workplace.

Hepatitis B prevalence and incidence in the fishing communities of Lake Victoria, Uganda: a retrospective cohort study.

INTRODUCTION: Hepatitis B is a serious potentially fatal hepatocellular disease caused by the hepatitis B virus. In the fishing communities of Lake Victoria Uganda, the hepatitis B virus infection burden is largely unknown. This study assessed the prevalence and incidence of hepatitis B in these communities. METHODS: This was a retrospective cohort study that tested serum samples collected from 13 to 49-year-old study participants that were residing in two Ugandan Lake Victoria fishing communities of Kasenyi (a mainland) and Jaana (an island). The samples were collected between 2013 and 2015 during the conduct of an HIV epidemiological cohort study in these communities. A total of 467 twelve-month follow-up and 50 baseline visit samples of participants lost to follow-up were tested for hepatitis B serological markers to determine prevalence. To determine hepatitis B virus incidence, samples that were hepatitis B positive at the follow-up visit had their baseline samples tested to identify hepatitis B negative samples whose corresponding follow-up samples were thus incident cases. RESULTS: The baseline mean age of the 517 study participants was 31.1 (SD ± 8.4) years, 278 (53.8%) of whom were females. A total of 36 (7%) study participants had hepatitis B virus infection, 22 (61.1%) of whom were male. Jaana had a higher hepatitis B virus prevalence compared to Kasenyi (10.2% vs 4.0%). In total, 210 (40.6%) study participants had evidence of prior hepatitis B virus infection while 48.6% had never been infected or vaccinated against this disease. A total of 20 (3.9%) participants had results suggestive of prior hepatitis B vaccination. Hepatitis B incidence was 10.5 cases/100PY (95% CI: 7.09-15.53). Being above 25 years of age and staying in Jaana were significant risk factors for hepatitis B virus acquisition (AOR 1.6, 95% CI: 1.1-2.2; p < 0.01 and 1.4, 95% CI: 1.1-1.8; p < 0.01 respectively). CONCLUSION: Hepatitis B virus incidence in Lake Victoria fishing communities of Uganda is very high, particularly in the islands. Interventions to lower hepatitis B virus transmission in these communities are urgently needed.

Mobility for maternal health among women in hard-to-reach fishing communities on Lake Victoria, Uganda; a community-based cross-sectional survey.

BACKGROUND: Maternal mortality is still a challenge in Uganda, at 336 deaths per 100,000 live births, especially in rural hard to reach communities. Distance to a health facility influences maternal deaths. We explored women's mobility for maternal health, distances travelled for antenatal care (ANC) and childbirth among hard-to-reach Lake Victoria islands fishing communities (FCs) of Kalangala district, Uganda. METHODS: A cross sectional survey among 450 consenting women aged 15-49 years, with a prior childbirth was conducted in 6 islands FCs, during January-May 2018. Data was collected on socio-demographics, ANC, birth attendance, and distances travelled from residence to ANC or childbirth during the most recent childbirth. Regression modeling was used to determine factors associated with over 5 km travel distance and mobility for childbirth. RESULTS: The majority of women were residing in communities with a government (public) health facility [84.2 %, (379/450)]. Most ANC was at facilities within 5 km distance [72 %, (157/218)], while most women had travelled outside their communities for childbirth [58.9 %, (265/450)]. The longest distance travelled was 257.5 km for ANC and 426 km for childbirth attendance. Travel of over 5 km for childbirth was associated with adolescent girls and young women (AGYW) [AOR = 1.9, 95 % CI (1.1-3.6)], up to five years residency duration [AOR = 1.8, 95 % CI (1.0-3.3)], and absence of a public health facility in the community [AOR = 6.1, 95 % CI (1.4-27.1)]. Women who had stayed in the communities for up to 5 years [AOR = 3.0, 95 % CI (1.3-6.7)], those whose partners had completed at least eight years of formal education [AOR = 2.2, 95 % CI (1.0-4.7)], and those with up to one lifetime birth [AOR = 6.0, 95 % CI (2.0-18.1)] were likely to have moved to away from their communities for childbirth. CONCLUSIONS: Despite most women who attended ANC doing so within their communities, we observed that majority chose to give birth outside their communities. Longer travel distances were more likely among AGYW, among shorter term community residents and where public health facilities were absent. TRIAL REGISTRATION: PACTR201903906459874 (Retrospectively registered). https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=5977 .

Defining adequate contact for transmission of Mycobacterium tuberculosis in an African urban environment.

BACKGROUND: The risk of infection from respiratory pathogens increases according to the contact rate between the infectious case and susceptible contact, but the definition of adequate contact for transmission is not standard. In this study we aimed to identify factors that can explain the level of contact between tuberculosis cases and their social networks in an African urban environment. METHODS: This was a cross-sectional study conducted in Kampala, Uganda from 2013 to 2017. We carried out an exploratory factor analysis (EFA) in social network data from tuberculosis cases and their contacts. We evaluated the factorability of the data to EFA using the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO). We used principal axis factoring with oblique rotation to extract and rotate the factors, then we calculated factor scores for each using the weighted sum scores method. We assessed construct validity of the factors by associating the factors with other variables related to social mixing. RESULTS: Tuberculosis cases (N = 120) listed their encounters with 1154 members of their social networks. Two factors were identified, the first named "Setting" captured 61% of the variance whereas the second, named 'Relationship' captured 21%. Median scores for the setting and relationship factors were 10.2 (IQR 7.0, 13.6) and 7.7 (IQR 6.4, 10.1) respectively. Setting and Relationship scores varied according to the age, gender, and nature of the relationship among tuberculosis cases and their contacts. Family members had a higher median setting score (13.8, IQR 11.6, 15.7) than non-family members (7.2, IQR 6.2, 9.4). The median relationship score in family members (9.9, IQR 7.6, 11.5) was also higher than in non-family members (6.9, IQR 5.6, 8.1). For both factors, household contacts had higher scores than extra-household contacts (p < .0001). Contacts of male cases had a lower setting score as opposed to contacts of female cases. In contrast, contacts of male and female cases had similar relationship scores. CONCLUSIONS: In this large cross-sectional study from an urban African setting, we identified two factors that can assess adequate contact between tuberculosis cases and their social network members. These findings also confirm the complexity and heterogeneity of social mixing.

Components of antenatal care received by women in fishing communities on Lake Victoria, Uganda; a cross sectional survey.

BACKGROUND: Uganda has one of the highest maternal deaths at a ratio of 336 per 100,000 live births. As Uganda strives to achieve sustainable development goals, appropriate antenatal care is key to reduction of maternal mortality. We explored women's reported receipt of seven of the Uganda guidelines components of antenatal care, and associated factors in hard to reach Lake Victoria island fishing communities of Kalangala district. METHODS: A cross sectional survey among 486 consenting women aged 15-49 years, who were pregnant at any time in the past 6 months was conducted in 6 island fishing communities of Kalangala district, Uganda, during January-May 2018. Interviewer administered questionnaires, were used to collect data on socio-demographics and receipt of seven of the Uganda guidelines components of antenatal care. Regression modeling was used to determine factors associated with receipt of all seven components. RESULTS: Over three fifths (65.0%) had at least one ANC visit during current or most recent pregnancy. Fewer than a quarter of women who reported attending care at least four times received all seven ANC components [(23.6%), P < 0.05]. Women who reported receipt of ANC from the mainland were twice as likely to have received all seven components as those who received care from islands (aOR = 1.8; 95% CI:0.9-3.7). Receipt of care from a doctor was associated with thrice likelihood of receiving all components relative to ANC by a midwife or nurse (aOR = 3.2; 95% CI:1.1-9.1). CONCLUSIONS: We observed that the delivery of antenatal care components per Ugandan guidelines is poor in these communities. Cost effective endeavors to improve components of antenatal care received by women are urgently needed. Task shifting some components of ANC to community health workers may improve care in these island communities. TRIAL REGISTRATION: PACTR201903906459874 (Retrospectively registered).

Acceptability of HIV testing for men attending televised football venues in Uganda.

BACKGROUND: Worldwide, HIV remains a major public health challenge, especially in Sub-Saharan Africa. Literature indicates that men's involvement in HIV testing, care, and treatment services is lower compared to women, therefore novel approaches are required to engage men in the cascade of HIV care. This study aimed to explore men's perception on the provision of HIV testing services in venues where English Premier League football games are televised. METHODS: An exploratory qualitative study was conducted between February and May 2018. Six focus group discussions were conducted with 50 conveniently selected men aged 18 years and older using a pre-tested discussion guide. All focus group discussions were audio recorded, transcribed verbatim, and analyzed thematically. RESULTS: Overall, HIV testing at venues telecasting English Premier League football games was acceptable to men. There was a very strong preference for health workers providing testing and counseling services be external or unknown in the local community. Possible motivators for testing services provided in these settings include subsidizing or eliminating entrance fee to venues telecasting games, integrating testing and counseling with health promotion or screening for other diseases, use of local football games as mobilization tools and use of expert clients as role models. CONCLUSIONS: This study suggests that HIV testing services at venues where EPL football games are televised is generally acceptable to men. In implementing such services, consideration should be given to preferences for external or unknown health workers and the motivating factors contributing to the use of these services. Given that HIV testing is currently not conducted in these settings, further research should be conducted to evaluate the feasibility of this approach as a means of enhancing HIV testing among Ugandan men.

Retention of HIV infected pregnant and breastfeeding women on option B+ in Gomba District, Uganda: a retrospective cohort study.

BACKGROUND: Lifelong antiretroviral therapy for HIV infected pregnant and lactating women (Option B+) has been rapidly scaled up but there are concerns about poor retention of women initiating treatment. However, facility-based data could underestimate retention in the absence of measures to account for self-transfers to other facilities. We assessed retention-in-care among women on Option B+ in Uganda, using facility data and follow-up to ascertain transfers to other facilities. METHODS: In a 25-month retrospective cohort analysis of routine program data, women who initiated Option B+ between March 2013 and March 2015 were tracked and interviewed quantitatively and qualitatively (in-depth interviews). Kaplan Meier survival analysis was used to estimate time to loss-to-follow-up (LTFU) while multivariable Cox proportional hazards regression was applied to estimate the adjusted predictors of LTFU, based on facility data. Thematic analysis was done for qualitative data, using MAXQDA 12. Quantitative data were analyzed with STATA® 13. RESULTS: A total of 518 records were reviewed. The mean (SD) age was 26.4 (5.5) years, 289 women (55.6%) attended primary school, and 53% (276/518) had not disclosed their HIV status to their partners. At 25 months post-ART initiation, 278 (53.7%) were LTFU based on routine facility data, with mean time to LTFU of 15.6 months. Retention was 60.2 per 1000 months of observation (pmo) (95% CI: 55.9-64.3) at 12, and 46.3/1000pmo (95% CI: 42.0-50.5) at 25 months. Overall, 237 (55%) women were successfully tracked and interviewed and 43/118 (36.4%) of those who were classified as LTFU at facility level had self-transferred to another facility. The true 25 months post-ART initiation retention after tracking was 71.3% (169/237). Women < 25 years, aHR = 1.71 (95% CI: 1.28-2.30); those with no education, aHR = 5.55 (95% CI: 3.11-9.92), and those who had not disclosed their status to their partners, aHR = 1.59 (95% CI: 1.16-2.19) were more likely to be LTFU. Facilitators for Option B+ retention based on qualitative findings were adequate counselling, disclosure, and the desire to stay alive and raise HIV-free children. Drug side effects, inadequate counselling, stigma, and unsupportive spouses, were barriers to retention in care. CONCLUSIONS: Retention under Option B+ is suboptimal and is under-estimated at health facility level. There is need to institute mechanisms for tracking of women across facilities. Retention could be enhanced through strategies to enhance disclosure to partners, targeting the uneducated, and those < 25 years.