Perspectives of female sex workers on HIV pre-exposure prophylaxis delivery in Uganda: A qualitative study.

Background: HIV pre-exposure prophylaxis (PrEP) is underutilized by cisgender female sex workers (FSW) despite its proven effectiveness. This study aimed to understand the experiences of FSW with PrEP services in Uganda to inform HIV programming for this key population. Methods: We conducted qualitative interviews with 19 FSW between June and July 2022 at the Most at Risk Populations Initiative clinic, Mulago Hospital, Kampala, to explore experiences with accessing PrEP Indepth interviews explored: (1) descriptions of where and how PrEP was obtained; (2) perspectives on current approaches for accessing PrEP; and (3) individual encounters with PrEP services. Data were analyzed through inductive thematic analysis. Results: Three key themes emerged for FSW perspectives on PrEP service delivery. FSW highlighted the positive impact of a welcoming clinic environment, which motivated FSW to initiate PrEP and fostered a sense of connectedness within their community. They also reported feeling accepted, secure, and free from prejudice when accessing PrEP through facility-based services. The second explores the obstacles faced by FSW, such as lengthy wait times at clinics, inadequate provider support, and lack of sensitivity training which hindered their access to PrEP The third sheds light on how HIV-related stigma negatively impacted the delivery of community-based PrEP for FSW. While community-based distribution offered convenience and helped mitigate stigma, clinic-based care provided greater anonymity and was perceived as offering higher-quality care. Overall, FSWs emphasized the critical role of friendly healthcare providers, social support, and non-stigmatizing environments in promoting successful utilization of PrEP. Conclusion: The study findings offer insights that can support HIV programs in optimizing PrEP delivery for FSW. Establishing easily accessible drug pick-up locations, prioritizing privacy, addressing and improving health workers' attitudes, and providing regular reminders could enhance PrEP access for FSW and decrease HIV acquisition.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective, cross-sectional, diagnostic accuracy study.

BACKGROUND: Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART). METHODS: 897 ART-initiators were recruited irrespective of symptoms and sputum induction offered. For triage (n=800), we evaluated point-of-care blood-based CRP testing, compared with the WHO-recommended four-symptom screen (W4SS). For sputum-based confirmatory testing (n=787), we evaluated Xpert Ultra versus Xpert MTB/RIF (Xpert). For urine-based confirmatory testing (n=732), we evaluated Xpert Ultra and LF-LAM. We used a sputum culture reference standard. FINDINGS: 463 (52%) of 897 participants were female. The areas under the receiver operator characteristic curves for CRP was 0·78 (95% CI 0·73-0·83) and for number of W4SS symptoms was 0·70 (0·64-0·75). CRP (≥10 mg/L) had similar sensitivity to W4SS (77% [95% CI 68-85; 80/104] vs 77% [68-85; 80/104]; p>0·99] but higher specificity (64% [61-68; 445/696] vs 48% [45-52; 334/696]; p<0·0001]; reducing unnecessary confirmatory testing by 138 (95% CI 117-160) per 1000 people and number-needed-to-test from 6·91 (95% CI 6·25-7·81) to 4·87 (4·41-5·51). Sputum samples with Xpert Ultra, which required induction in 49 (31%) of 158 of people (95% CI 24-39), had higher sensitivity than Xpert (71% [95% CI 61-80; 74/104] vs 56% [46-66; 58/104]; p<0·0001). Of the people with one or more confirmatory sputum or urine test results that were positive, the proportion detected by Xpert Ultra increased from 45% (26-64) to 66% (46-82) with induction. Programmatically done haemoglobin, triage test combinations, and urine tests showed comparatively worse results. INTERPRETATION: CRP is a more specific triage test than W4SS in those initiating ART. Sputum induction improves diagnostic yield. Sputum samples with Xpert Ultra is a more accurate confirmatory test than with Xpert. FUNDING: South African Medical Research Council, EDCTP2, US National Institutes of Health-National Institute of Allergy and Infectious Diseases.

HIV pre-exposure prophylaxis uptake, retention and adherence among female sex workers in sub-Saharan Africa: a systematic review.

OBJECTIVE: To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA). DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022. ELIGIBILITY CRITERIA FOR STUDIES: Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA. DATA EXTRACTION AND SYNTHESIS: Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention. RESULTS: Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26). CONCLUSIONS: A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs. PROSPERO REGISTRATION NUMBER: CRD42020219363.

Acceptance of assisted partner notification among HIV-positive adults with severe mental illness at a national referral hospital in Uganda: a cross-sectional study.

BACKGROUND: HIV mostly affects people with severe mental illnesses (SMIs) than the general population. In 2015, the World Health Organization (WHO) introduced assisted partner notification (APN) as a strategy to increase HIV testing. Although research has demonstrated the effectiveness of APN in the general population, its use among people living with HIV (PLHIV) who have SMI is not well understood. This study sought to determine the acceptance of the APN strategy among PLHIV who had a diagnosis of SMI. METHODS: This study used a cross-sectional study design that was retrospective to determine acceptance of APN among PLHIV with a documented diagnosis of SMI. We enrolled participants with a diagnosis of both HIV and SMI from August 2018 to January 2022, attending the HIV clinic at Butabika Hospital. We used pretested questionnaires to extract participants' demographic and clinical data from their existing clinical charts, antiretroviral therapy (ART) registers and APN registers. We defined acceptance of APN as the number of PLHIV with SMI diagnoses who agreed to provide information about their sexual partners. We used modified Poisson regression analysis to assess the factors associated with the acceptance of APN. RESULTS: A total of 125 participants were enrolled, of whom 83 (66.4%) were female. The median age was 30 (interquartile range (IQR) (25-34)), and 41 (33%) of them accepted APN (95% CI: 25.05-41.61). Receipt of at least three counselling sessions before enrollment in APN (aPR = 1.8, 95% CI: 1.72-1.98) was the most significant factor associated with increased acceptance of APN. Poor adherence to ART (aPR = 0.62, 95% CI: 0.54-0.80), being escorted to hospital by a distant relative (aPR = 0.55, 95% CI: 0.39-0.80), being married/cohabiting (aPR = 0.65, 95% CI: 0.60-0.81), and being a Seventh Day Adventist (SDA) (aPR = 0.53, 95% CI: 0.45-0.71) or Pentecostal (aPR = 0.44, 95% CI: 0.22-0.98) by faith were associated with reduced acceptance of APN. CONCLUSION AND RECOMMENDATION: The acceptance of APN is low among PLHIV with a diagnosis of SMI. More structured counselling would facilitate earlier identification of undiagnosed HIV-positive partners. We recommend a follow-up study to compare acceptance of APN among PLHIV with SMI and those without SMI.

Mortality and associated factors among people living with HIV admitted at a tertiary-care hospital in Uganda: a cross-sectional study.

BACKGROUND: Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. METHODS: We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. RESULTS: Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31-49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25-343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1-7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13-1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33-1.91, p < 0.001; undocumented CD4 + cell count status 2.08, 95%CI 1.73-2.50, p < 0.001; impaired function status 7.35, 95%CI 6.42-8.41, p < 0.001; COVID-19 1.70, 95%CI 1.22-2.37, p 0.002; liver disease 1.77, 95%CI 1.36-2.30, p < 0.001; co-infections 1.53, 95%CI 1.32-1.78, p < 0.001; home address > 20 km from hospital 1.23, 95%CI 1.04-1.46, p 0.014; hospital readmission 0.7, 95%CI 0.56-0.88, p 0.002; chronic lung disease 0.62, 95%CI 0.41-0.92, p 0.019; and neurologic disease 0.46, 95%CI 0.32-0.68, p < 0.001. CONCLUSION: One in four admitted PLHIV die during hospitalization. Identification of risk factors (such as ART interruption, function impairment, low/undocumented CD4 + cell count), early diagnosis and treatment of co-infections and liver disease could improve outcomes.

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.

Health provider perspectives of Village Health Team-delivered oral HIV self-testing among men in Central Uganda: a qualitative evaluation using RE-AIM framework.

Background: HIV self-testing (HIVST) is a practical and effective way to provide HIV testing services to at-risk and underserved populations, particularly men. Utilizing Village Health Teams (VHTs) could enhance community-based delivery of oral HIVST to reach the last un-tested individuals who may be at-risk of infection. However, little is known about what VHTs and facility-based healthcare workers think about facilitating oral HIVST and delivery of subsequent HIV services. We investigated the views of health providers on oral HIVST delivered by VHTs among men in rural communities in Central Uganda. Methods: We conducted a qualitative study in Mpigi district, interviewing 27 health providers who facilitated oral HIV self-testing among men. The providers consisting of 15 VHTs and 12 facility-based health workers were purposively selected. All interviews were audio-recorded, transcribed verbatim, and translated to English for a hybrid inductive-deductive thematic analysis. We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Implementation Science framework to generate and categorize open codes. Results: In terms of reaching men with HIV testing services, the providers considered HIVST to be a fast and convenient method, which could boost HIV testing. However, they also had concerns about its accuracy. In terms of effectiveness, HIVST was perceived as a reliable, user-friendly, and efficient approach to HIV testing. However, it depended on the user's preference for testing algorithms. Regarding adoption, HIVST was considered to enhance autonomy, well-suited for use in the community, and offered opportunities for linkage and re-linkage into care. However, at times HIVST faced hesitance. As for Implementation, VHTs had various support roles in HIVST but had concerns about social insecurities and delays in seeking subsequent facility-based services after HIVST. Regarding Maintenance, providers recommended several ways to improve oral HIVST including; optimizing tracking of HIVST distribution and use, improving linkage and retention in care after HIVST, diversifying HIVST for combined HIV prevention packages and including more languages, broadening sensitization among potential HIVST users and health providers, differentiating distribution models, and prioritizing targeted HIVST efforts. Conclusion: HIVST has the potential to increase testing rates and engagement of men in HIV services. However, for it to be implemented on a population-wide scale, continuous sensitization of potential users and health providers is necessary, along with streamlined structures for tracking kit distribution, use, and reporting of results. Further implementation research may be necessary to optimize the role of health providers in facilitating HIVST.

Determinants to Continuation on Hiv Pre-exposure Propylaxis Among Female Sex Workers at a Referral Hospital in Uganda: a Mixed Methods Study Using Com-b Model.

Background: Female sex workers (FSWs) have the highest HIV prevalence in Uganda. Pre exposure prophylaxis (PrEP) has been recommended as part of the HIV combination prevention strategy, with improved patient initiation, but continuation on the service is low. We evaluated PrEP continuation among FSWs and explored potential determinants of PrEP continuation within a public referral hospital in Urban Uganda. Methods: An explanatory sequential mixed method study was conducted at Kiruddu National referral hospital in Uganda. Secondary data on social demographic characteristics and follow up outcomes of at least one year was collected for all FSWs who were initiated PrEP between May 2020 and April 2021.We used Kaplan-Meier survival analysis to evaluate continuation on PrEP from time of initiation and follow-up period. The capability, opportunity, and motivation to change behaviour model was used to explore perspectives and practices of FSWs (n = 24) and health care providers (n = 8) on continuation on PrEP among FSWs, using semi structured interviews. The qualitative data was deductively coded and analyzed thematically, categorizing the themes related to PrEP continuation as facilitators and barriers. Results: Of the 292 FSWs initiated on PrEP during this period, 101 (34.6) % were active on PrEP, 137 (46.9%) were lost to follow-up, 45 (15.4%) were no longer eligible to continue PrEP, eight (2.7%) were transferred out and one (0.3%) had died. Median survival time on PrEP was 15 months (Interquartile range IQR, 3-21). The continuation rates on PrEP at six (6) and 12 months were, 61.1% and 53.1%, respectively. Facilitators of PrEP continuation included awareness of risk associated with sex work, integration of PrEP with other HIV prevention services, presence of PrEP Peer support and use of Drop-in centers. The barriers included low community awareness about PrEP, high mobility of sex workers, substance abuse, and the unfavorable daytime clinic schedules. Conclusion: Continuation on PrEP remains low among FSWs. Interventions for PrEP continuation should address barriers such as low community awareness on PrEP, substance abuse and restrictive health facility policies for scale of the PrEP program among FSWs in Uganda. Integration of PrEP with other services and scale up of community PrEP delivery structures may improve its continuation.

Clinical characteristics and morbidity among hospitalized adults with advanced HIV disease in Uganda during 'test and treat' era.

Nearly four decades after the first case of AIDS was described, the global number of AIDS-related deaths has steadily declined but falls short of the elimination targets, especially in sub-Saharan Africa. Despite interventions to promote early HIV diagnosis and treatment, hospitalization and mortality related to advanced HIV disease (AHD) remains a significant public health problem in Uganda. We assessed the HIV treatment history and causes of hospitalization among in-patients with AHD at a tertiary hospital in Uganda. In this cross-sectional study, pre-hospitalization HIV treatment history and clinical characteristics of HIV-positive in-patients with CD4<200 cells/µL or WHO stage 3 or 4 clinical events were assessed. Descriptive data were summarized using percentages and medians. Among hospitalized adults with AHD from November 2021 to June 2022, 74% (260/353) knew their HIV status prior to hospitalization and 62% (219/353) were ART experienced at presentation. The median time since ART initiation was 28 months (IQR; 2-97). Overall, 73% (258/353) had at least two etiological diagnoses and the majority (non-mutually exclusive) were diagnosed with tuberculosis (61.2%), cryptococcal meningitis (20.7%), mucosal candidiasis (16.1%) and bacterial infections (15%). In conclusion, nearly two-thirds of in-patients with advanced HIV disease were ART experienced prior to hospitalization and tuberculosis was the most common cause of hospitalization. Innovative strategies to strengthen HIV diagnosis, linkage, and retention in HIV care and to increase coverage of TB preventive therapy are urgently needed.

Perceptions and factors associated with the uptake of the community client-led antiretroviral therapy delivery model (CCLAD) at a large urban clinic in Uganda: a mixed methods study.

INTRODUCTION: Community Client-Led ART Delivery (CCLAD) is a community HIV care model. In this model, a group of persons living with HIV (PLHIV) in a specific location, take turns going to the HIV clinic to pick up Antiretroviral Treatment refills for members. The uptake of this model, however, remains low despite its improvements in patient retention. In this study, we explored PLHIV's perceptions of this model and identified the factors associated with its low uptake. METHODS: This was a mixed methods study based on a retrospective review of records of PLHIV and in-depth interviews. We reviewed the medical records of people receiving ART to determine their current model of ART delivery and conducted in-depth interviews with 30 participants who were eligible to be enrolled in the CCLAD model at the Mulago ISS clinic. We performed logistic regression to identify factors associated with the uptake of the CCLAD model and inductive thematic analysis to explore PLHIV's perceptions of the CCLAD model. RESULTS: A total of 776 PLHIV were sampled for the study, 545 (70.2%) of whom were female. The mean age (standard deviation) was 42 (± 9.3) years. Overall, 55 (7.1%) received ART using the CCLAD model. Compared to other ART-delivery models, CCLAD was associated with being on ART for at least eight years (AOR 3.72; 95% CI: 1.35-10.25) and having no prior missed clinic appointments (AOR 10.68; 95% CI: 3.31-34.55). Mixed perceptions were expressed about the CCLAD model. Participants interviewed appreciated CCLAD for its convenience and the opportunities it offered members to talk and support each other. Others however, expressed concerns about the process of group formation, and feeling detached from the health facility with consequences of lack of confidentiality. CONCLUSION: The current uptake of the CCLAD model is lower than the national recommended percentage of 15%. Its uptake was associated with those who had been in care for a longer period and who did not miss appointments. Despite CCLAD being perceived as convenient and as promoting support among members, several challenges were expressed. These included complexities of group formation, fear of stigma and feelings of detachment from health facilities among others. So, while CCLAD presents a promising alternative ART delivery model, more attention needs to be paid to the processes of group formation and improved patient monitoring to address the feelings of detachment from the facility and facility staff.

Preferences of people living with HIV for features of tuberculosis preventive treatment regimens - a discrete choice experiment.

Background: Tuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens. Methods: We conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. In nine random choice tasks, participants chose between two hypothetical TPT regimens with different features (pills per dose, frequency, duration, need for adjusted antiretroviral therapy [ART] dosage and side effects). We analyzed preferences using hierarchical Bayesian estimation, latent class analysis, and willingness-to-trade simulations. Results: Of 400 PLHIV, 392 (median age 44, 72% female, 91% TPT-experienced) had high quality choice task responses. Pills per dose was the most important attribute (relative importance 32.4%, 95% confidence interval [CI] 31.6 - 33.2), followed by frequency (20.5% [95% CI 19.7 - 21.3]), duration (19.5% [95% CI 18.6 - 20.5]), and need for ART dosage adjustment (18.2% [95% CI 17.2 - 19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing (N=222; 57%); another was averse to ART dosage adjustment (N=107; 27%); and the last prioritized short and tolerable regimens (N=63; 16%). All groups highly valued fewer pills per dose. Participants were willing to accept a regimen of 2.8 months' additional duration [95% CI: 2.4 - 3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4 - 4.8] months for weekly rather than daily dosing, and 2.2 [95% CI 1.3 - 3.0] months to avoid ART dosage adjustment. Conclusions: To align with preferences of PLHIV, decision-makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing, and no need for ART dosage adjustment, rather than focus primarily on duration of treatment.

HIV viral load suppression among people with mental disorders at two urban HIV clinics in Uganda: a parallel convergent mixed methods study using the social ecological model.

BACKGROUND: Uganda adopted and implemented the Universal Test and Treat (UTT) guidelines in 2017, which require HIV-infected persons to be initiated on antiretroviral therapy (ART) at any CD4 + cell count, and to be routinely monitored for viral load to assess response to ART. However, there is paucity of data on viral load suppression (VLS) among people living with HIV (PLHIV) with mental disorders. We conducted a parallel convergent mixed methods study to determine HIV VLS among people with a mental disorder and explored the socio-cultural determinants of VLS at Butabika hospital and Mulago (ISS) HIV Clinics in Uganda. METHODS: We conducted a retrospective medical records review; seven key informant interviews (KII) among purposively selected healthcare providers and 12 in-depth interviews (IDI) among clinically stable PLHIV with a mental disorder. Data was collected on demographics, mental disorder, ART, viral load status, social support, stigma, and disclosure of HIV status. Quantitative data was analysed using descriptive statistics and modified Poisson regression, while Inductive thematic analysis was used for the qualitative data. RESULTS: Of the 240 PLHIV with a mental disorder who were enrolled, 161 (67.1%) were female with mean age 38.9 (± 11.2) years. Overall, 88.8% (95% Cl: 84.0 - 92.2%) achieved VLS. Age (aPR = 1.00, 95%Cl = 1.00-1.00), male gender (aPR = 0.90, 95%Cl = 0.82-0.98), divorced (aPR = 0.88, 95%Cl = 0.82-0.94), widowed (aPR = 0.84, 95%Cl = 0.83-0.86), baseline CD4 count < 200 (aPR = 0.89, 95%Cl = 0.85-0.94), psychotic mental disorders (aPR = 1.11; 95%CI = 1.08-1.13) and fair (85-94%) ART adherence level (aPR = 0.69, 95%Cl = 0.55-0.87) and TDF/3TC/DTG (aPR = 0.92; 95%CI = 0.91-0.94) were associated with HIV VLS. Social support from family members, knowledge of impact of negative thoughts on VLS, fear of breaking up with partners and compassionate healthcare providers positively influenced VLS. Stigma and discrimination from the community, self-perceived stigma hindering social relations, socio-economic challenges and psychiatric drug stock-outs negatively affected VLS. CONCLUSION AND RECOMMENDATIONS: HIV VLS among PLHIV with mental disorders at institutions that provide integrated HIV and mental health care is still below the UNAIDS 95% target. Health promotion messaging focusing on benefits of VLS and countering stigma to create a safe environment; and active involvement of family members in care could improve HIV treatment outcomes for PLHIV with mental disorders.

Effect of the COVID-19 lockdown on the HIV care continuum in Southwestern Uganda: A time series analysis.

INTRODUCTION: In Uganda, COVID-19 lockdown policies curbed the spread of SARS-CoV-2, but their effect on HIV care is poorly understood. OBJECTIVES: We examined the effects of COVID-19 lockdown policies on ART initiation, missed visits, and viral suppression in Uganda. METHODS: We conducted a time series analysis using data from a dynamic cohort of persons with HIV enrolled between March 2017 and September 2021 at HIV clinics in Masaka and Mbarara Regional Referral Hospitals in Southwestern Uganda. Poisson and fractional probit regression were used to predict expected monthly antiretroviral therapy initiations, missed visits, and viral suppression based on pre-lockdown trends. Observed and expected trends were compared across three policy periods: April 2020-September 2021 (overall), April-May 2020 (1st lockdown), and June-August 2021 (2nd lockdown). RESULTS: We enrolled 7071 Persons living with HIV (PWH) (nMasaka = 4150; nMbarara = 2921). Average ART duration was 34 and 30 months in Masaka and Mbarara, respectively. During the 18-month post-lockdown period, monthly ART initiations were lower than expected in both Masaka (51 versus 63 visits; a decrease of 12 [95% CI: -2, 31] visits) and Mbarara (42 versus 55 visits; a decrase of 13 [95% CI: 0, 27] visits). Proportion of missed visits was moderately higher than expected post-lockdown in Masaka (10% versus 7%; 4% [95% CI: 1%, 7%] absolute increase), but not in Mbarara (13% versus 13%; 0% [95% CI: -4%, 6%] absolute decrease). Viral suppression rates were moderate-to-high in Masaka (64.7%) and Mbarara (92.5%) pre-lockdown and remained steady throughout the post-lockdown period. CONCLUSION: The COVID-19 lockdown in Uganda was associated with reductions in ART initiation, with minimal effects on retention and viral suppression, indicating a resilient HIV care system.

Perspectives of people living with HIV on barriers to timely ART initiation following referral for antiretroviral therapy: A qualitative study at an urban HIV clinic in Kampala, Uganda.

Early initiation of antiretroviral therapy (ART) after HIV diagnosis prevents HIV transmission, progression of HIV to AIDS and improves quality of life. However, little is known about the barriers to timely ART initiation among patients who test HIV positive in settings different from where they will receive HIV treatment, hence are referred in the routine setting. Therefore, we explored the perspectives of people living with HIV on barriers faced to initiate ART following HIV testing and referral for treatment. In this qualitative study, we purposively sampled and enrolled 17 patients attending the Mulago ISS clinic. We selected patients (≥18 years) who previously were received as referrals for HIV treatment and had delayed ART initiation, as ascertained from their records. We conducted in-depth interviews, which were audio recorded, transcribed and translated. We used Atlas.ti version 9 software for data management. Data analysis followed thematic and framework analysis techniques and we adopted the socio-ecological model to categorize final themes. Key themes were found at organizational level including; negative experiences at the place of HIV diagnosis attributed to inadequate counselling and support, unclear communication of HIV-positive results and ambiguous referral procedures; and, long waiting time when patients reached the HIV clinic. At individual level, the themes identified were; immediate denial with late acceptance of HIV-positive results attributed to severe emotional and psychological distress at receiving results, fear of perceived side effects and long duration on ART. At interpersonal level, we found that anticipated and enacted stigma after HIV diagnosis resulted in non-disclosure, discrimination and lack of social support. We found that challenges at entry (during HIV test) and navigation of the HIV care system in addition to individual and interpersonal factors contributed to delayed ART initiation. Interventions during HIV testing would facilitate early ART initiation among patients referred for HIV care.

Factors associated with willingness to take Pre-Exposure Prophylaxis (PrEP) among high-risk adolescent boys and young men in Masese fishing community, Uganda.

Pre-Exposure Prophylaxis (PrEP) is a known HIV prevention strategy for high-risk populations however, some high-risk communities have not yet fully embraced it. We sought to determine willingness to take PrEP and the associated factors among high-risk adolescent boys and young men (ABYM) in Masese fishing community, Jinja district, Eastern Uganda. We conducted a cross-sectional study, between October and November 2020, using a semi-structured questionnaire among ABYM aged 10-24 years in Masese fishing community, Eastern Uganda. We surveyed 479 participants, who had two or more sexual partners with inconsistent or no condom use. We carried out modified Poisson regression analysis to determine factors associated with willingness to take PrEP.Of 479 high-risk ABYM, 86.4% (n = 414) were willing to take PrEP. Confidence in PrEP safety (adj.PR = 1.56; 95%CI: 1.55, 2.24), availability of PrEP in areas easily accessible by ABYM (adj.PR = 1.40; 95%CI: 1.25, 1.57), and perceiving oneself as being at a very high risk of HIV infection (adj.PR = 1.11; 95%CI: 1.03, 1.20) were positively associated with willingness to take PrEP. On the other hand, being unmarried (adj.PR = 0.92; 95%CI: 0.87, 0.98) and earning more than USD 27 a month (adj.PR = 0.92; 95%CI: 0.87, 0.97) were negatively associated with willingness to take PrEP. There was high willingness to take PrEP among adolescent boys and young men in Masese fishing community. Confidence in PrEP safety, access to PrEP in their community and self-perception to be at high risk for HIV acquisition had a positive bearing on willingness to take PrEP while being unmarried and earning more than USD27 had a negative bearing on willingness to take PrEP. These findings suggest a need for target-specific interventions for unmarried men and those earning >USD27.

Uptake and perceptions of oral HIV self-testing delivered by village health teams among men in Central Uganda: A concurrent parallel mixed methods analysis.

The World Health Organization (WHO) recommends HIV self-testing (HIVST) to increase access to and utilization of HIV services among underserved populations. We assessed the uptake and perceptions of oral HIVST delivered by Village Health Teams (VHTs) among men in a peri-urban district in Central Uganda. We used a concurrent parallel mixed methods study design and analyzed data from 1628 men enrolled in a prospective cohort in Mpigi district, Central Uganda between October 2018 and June 2019. VHTs distributed HIVST kits and linkage-to-care information leaflets to participants in 30 study villages allowing up-to 10 days each to self-test. At baseline, we collected data on participant socio-demographics, testing history and risk behavior for HIV. During follow-up, we measured HIVST uptake (using self-reports and proof of a used kit) and conducted in-depth interviews to explore participants' perceptions of using HIVST. We used descriptive statistics to analyze the quantitative data and a hybrid inductive, and deductive thematic analysis for the qualitative data and integrated the results at interpretation. The median age of men was 28 years, HIVST uptake was 96% (1564/1628), HIV positivity yield was 4% (63/1564) and reported disclosure of HIVST results to sexual partners and significant others was 75.6% (1183/1564). Men perceived HIVST as a quick, flexible, convenient, and more private form of testing; allowing disclosure of HIV test results to sexual partners, friends and family, and receiving social support. Others perceived it as an opportunity for knowing or re-confirming their sero-status and subsequent linkage or re-linkage to care and prevention. Utilizing VHT networks for community-based delivery of HIVST is effective in reaching men with HIV testing services. Men perceived HIVST as highly beneficial but needed more training on performing the test and the integrating post-test counseling support to optimize use of the test for diagnosing HIV.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective diagnostic accuracy study.

Background: Tuberculosis (TB), a major cause of death in people living with HIV (PLHIV), remains challenging to diagnose. Diagnostic accuracy data are lacking for promising triage tests, such as C-reactive protein (CRP), and confirmatory tests, such as sputum and urine Xpert MTB/RIF Ultra (Ultra), and urine LAM, without prior symptom selection. Methods: 897 PLHIV initiating antiretroviral therapy were consecutively recruited in settings with high TB incidence, irrespective of symptoms. Participants were offered sputum induction, with a liquid culture reference standard. First, we evaluated point-of-care CRP testing on blood, compared to the World Health Organization (WHO)-recommended four-symptom screen (W4SS) for triage (n=800). Second, we evaluated Xpert MTB/RIF Ultra (Ultra) versus Xpert MTB/RIF (Xpert) for sputum-based confirmatory testing (n=787), with or without sputum induction. Third, we evaluated Ultra and Determine LF-LAM for urine-based confirmatory testing (n=732). Findings: CRP and number of W4SS symptoms had areas under the receiver operator characteristic curve of 0.78 (95% confidence interval 0.73, 0.83) and 0.70 (0.64, 0.75), respectively. For triage, CRP (≥10 mg/l) has similar sensitivity to W4SS [77% (68, 85) vs. 77% (68, 85); p>0.999] but higher specificity [64% (61, 68) vs. 48% (45, 52); p<0.001]; reducing unnecessary confirmatory testing by 138 per 1000 people and the number-needed-to-test from 6.91 (6.25, 7.81) to 4.87 (4.41, 5.51). Using sputum, which required induction in 31% (24, 39) of people, Ultra had higher sensitivity than Xpert [71% (61, 80) vs. 56% (46, 66); p<0.001] but lower specificity [98% (96, 100) vs. 99% (98, 100); p<0.001]. The proportion of people with ≥1 positive confirmatory result detected by Ultra increased from 45% (26, 64) to 66% (46, 82) when induction was done. Programmatically-done haemoglobin, triage test combinations, and urine tests showed comparatively worse performance. Interpretation: Among ART-initiators in a high burden setting, CRP is a more specific triage test than W4SS. Sputum induction improves yield. Sputum Ultra is a more accurate confirmatory test than Xpert. Funding: SAMRC (MRC-RFA-IFSP-01-2013), EDCTP2 (SF1401, OPTIMAL DIAGNOSIS), NIH/NIAD (U01AI152087). Research in context: Evidence before this study: Novel triage and confirmatory tests are urgently needed for TB, especially in key risk groups like PLHIV. Many TB cases do not meet World Health Organization (WHO)-recommended four-symptom screen (W4SS) criteria despite accounting for significant transmission and morbidity. W4SS also lacks specificity, which makes onward referral of triage-positive people for expensive confirmatory testing inefficient and hampers diagnostic scale-up. Alternative triage approaches like CRP have promise, but have comparatively little data in ART-initiators, especially when done without syndromic preselection and using point-of-care (POC) tools. After triage, confirmatory testing can be challenging due to sputum scarcity and paucibacillary early-stage disease. Next generation WHO-endorsed rapid molecular tests (including Xpert MTB/RIF Ultra; Ultra) are a standard-of-care for confirmatory testing. However, there are no supporting data in ART-initiators, among whom Ultra may offer large sensitivity gains over predecessors like Xpert MTB/RIF (Xpert). The added value of sputum induction to augment diagnostic sampling for confirmatory testing is also unclear. Lastly, the performance of urine tests (Ultra, Determine LF-LAM) in this population requires more data.Added value of this study: We evaluated repurposed and new tests for triage and confirmatory testing using a rigorous microbiological reference standard in a highly vulnerable high-priority patient population (ART-initiators) regardless of symptoms and ability to naturally expectorate sputum. We showed POC CRP triage is feasible, performs better than W4SS, and that combinations of different triage approaches offer no advantages over CRP alone. Sputum Ultra has superior sensitivity to Xpert; often detecting W4SS-negative TB. Furthermore, without induction, confirmatory sputum-based testing would not be possible in a third of people. Urine tests had poor performance. This study contributed unpublished data to systematic reviews and meta-analyses used by the WHO to inform global policy supporting use of CRP triage and Ultra in PLHIV.Implication of all the available evidence: POC CRP triage testing is feasible and superior to W4SS and, together with sputum induction in people who triage CRP-positive should, after appropriate cost and implementation research, be considered for roll-out in ART-initiators in high burden settings. Such people should be offered Ultra, which outperforms Xpert.

Uptake of community antiretroviral group delivery models for persons living with HIV in Arua district, Uganda: A parallel convergent mixed methods study.

Community antiretroviral groups (CAGs) is one of the innovative and efficient differentiated service delivery models (DSDM) for reaching persons needing human immunodeficiency virus (HIV) treatment in the community. Since DSDM adoption in Uganda, evidence suggests better care outcomes for patients in DSDM compared to counterparts in routine health facility care. However, uptake of CAG models for eligible community groups of persons living with HIV (PLHIV) has been slow in Arua district, Uganda and stakeholders' perceptions regarding its implementation unexplored. The objective of the study was to determine the uptake, barriers and facilitators influencing CAG model implementation in Arua district, Uganda. We conducted a parallel convergent mixed-methods study from March 2020 to December 2020 at Adumi health centre IV and Kuluva hospital in Arua district. We enrolled and extracted data for every fifth virally suppressed participant on antiretroviral therapy (ART) at the two health facilities. Data were analysed using STATA 13.0. Uptake was determined as the proportion of eligible PLHIV that were enrolled into a group. We performed logistic regression to determine factors associated with uptake. We conducted one focus group discussion per facility among healthcare workers involved in the management of PLHIV. We also conducted 7 focus group discussions among PLHIV across the two facilities. Thematic analysis was used to describe the data. A total of 399 PLHIV were eligible for CAG, 61.6% were female, and 44.9% were on dolutegravir (DTG) based regimen. Uptake was 6.8%, 95% CI (4.7-9.7) and was found to be significantly associated with being divorced or separated in a marriage (OR; 0.14, 95%CI; 0.02-0.92, P = 0.014). Members picking drugs in turns, comforting and encouraging others to take the drugs, and health workers advising them to join and stay with other group members were perceived as facilitators to uptake of community antiretroviral group delivery model. Having few and distant eligible members in the local area to form a group, lack of transport among the member to pick the drugs when it's their turn, misunderstandings and lack of confidentiality amongst the members, and lack of partner disclosure were perceived as barriers to uptake of community antiretroviral group delivery model. Uptake of community antiretroviral group delivery model in Arua district is very low. There may be a need to support community antiretroviral group delivery models with income- generating activities, transport facilitation, closer community drug pick-up points and improved partner disclosure support mechanisms among married group members.

Viral suppression among adults with HIV receiving routine dolutegravir-based antiretroviral therapy and 3 months weekly isoniazid-rifapentine.

OBJECTIVE: We aimed to evaluate safety of 3 months weekly isoniazid-rifapentine (3HP) for tuberculosis (TB) prevention when co-administered with dolutegravir-based antiretroviral therapy (TLD), and compare viral suppression among those initiating TLD + 3HP vs. TLD alone. DESIGN/METHODS: We analyzed data from an ongoing Phase 3 randomized trial comparing TB screening strategies among adults with CD4 + ≤350 cells/µl initiating routine antiretroviral therapy (ART) in Kampala, Uganda. TB screen-negative participants without contraindications are referred for self-administered 3HP. HIV viral load is routinely measured at 6 and 12 months. Here, we included TB-negative participants who initiated TLD with or without 3HP. We determined the number who discontinued 3HP due to drug toxicity. In addition, we assessed viral suppression at 6 and 12 months and used log-binomial regression to assess risk of viremia at 6 months for participants who initiated TLD + 3HP vs. TLD alone. RESULTS: Of 453 participants initiating TLD (287 [63.4%] female, median age 30 years [interquartile range (IQR) 25-37], median pre-ART CD4 + cell count 188 cells/µl [IQR 86-271]), 163 (36.0%) initiated 3HP. Of these, 154 (94.5%) completed 3HP and one (0.6%) had treatment permanently discontinued due to a possible 3HP-related adverse event. At 6 months, for participants who received TLD + 3HP, risk of viremia >50 copies/ml was 1.51 [95% confidence interval (CI) 1.07-2.14] times that of participants who received TLD alone. There was no difference in viral suppression between those who received TLD + 3HP vs. TLD alone at 12 months. CONCLUSIONS: Co-administration of TLD + 3HP was well tolerated. However, those who received TLD + 3HP were less likely to achieve viral suppression within six-months compared to those who received TLD alone.

Integration of COVID-19 and TB screening in Kampala, Uganda: healthcare provider perspectives.

BACKGROUND: Following the first wave of the COVID-19 outbreak, Uganda experienced a 40% drop in tuberculosis (TB) screening by June 2020. We sought to identify barriers to and facilitators of integrated COVID-19 and TB screening from the perspective of healthcare providers (HCPs) at a National Referral Hospital in Kampala, Uganda. DESIGN/METHODS: We conducted a cross-sectional study using in-depth interviews with 12 HCPs involved in TB activities in the outpatient and emergency departments at Kiruddu National Referral Hospital, Kampala, Uganda. We explored the HCP experiences at work in the setting of COVID-19, HCP perceived effect of COVID-19 on TB screening activities at the hospital, and perceptions about social and contextual factors that might influence the willingness of HCP to integrate screening of COVID-19 and TB. We analyzed the data using an inductive thematic approach and we denoted the emergent themes as barriers to and facilitators of COVID-19/TB integrated screening. We then mapped the themes to the Capability, Opportunity, Motivation, and Behavior (COM-B) model. RESULTS: The facilitators to integrated COVID-19 and TB screening included the availability of TB focal persons and already existing training forums at the hospital that could be utilized to strengthen the capacity of HCP to integrate COVID-19 and TB screening. The barriers included HCP's inadequate knowledge on how to integrate screening of COVID-19 and TB, the absence of simple easy-to-use standard operating procedures and data collection tools for integrated screening, inconsistent supply of personal protective equipment (PPE), understaffing, and fear of contracting COVID-19 infection. The identified intervention functions to address the facilitators or barriers included education, persuasion, enablement, and training. CONCLUSIONS: These findings provided a basis for designing contextually appropriate interventions targeting factors that are likely to influence HCP decisions and willingness to conduct TB screening in the context of COVID-19. Future studies should evaluate the effect of addressing these barriers to the integration of COVID-19 and TB as well as the effect of this on TB case finding in high-burden TB settings.