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.

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.

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.

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.

Predictors of delayed Anti-Retroviral Therapy initiation among adults referred for HIV treatment in Uganda: a cross-sectional study.

BACKGROUND: Uganda's current guidelines recommend immediate initiation of Anti-Retroviral Therapy (ART) for persons living with HIV in order to reduce HIV/AIDS related morbidity and mortality. However, not all eligible PLHIV initiate ART within the recommended time following HIV diagnosis. We assessed the prevalence and factors associated with delayed ART initiation among PLHIV referred for ART initiation, five years since rolling out the test and treat guidelines. METHODS: In this cross-sectional study, we enrolled adult patients referred to Mulago Immune Suppressive Syndrome (Mulago ISS) clinic for ART initiation from January 2017 to May 2021. We collected data on socio-demographics, HIV diagnosis and referral circumstances, and time to ART initiation using a questionnaire. The outcome of interest was proportion of patients that delayed ART, defined as spending more than 30 days from HIV diagnosis to ART initiation. We performed multivariable logistic regression and identified significant factors. RESULTS: A total of 312 patients were enrolled of which 62.2% were female. The median (inter-quartile range [IQR]) age and baseline CD4 count of the patients were 35 (28-42) years and 315 (118.8-580.5) cells/µL respectively. Forty-eight (15.4%) patients delayed ART initiation and had a median (IQR) time to ART of 92 (49.0-273.5) days. The factors associated with delayed ART initiation were; 1) having had the HIV diagnosis made from a private health facility versus public, (adjusted odds ratio [aOR] = 2.4 (95% confidence interval [CI] 1.1-5.5); 2) initial denial of positive HIV test results, aOR = 5.4 (95% CI: 2.0-15.0); and, 3) having not received a follow up phone call from the place of HIV diagnosis, aOR = 2.8 (95% CI: 1.2-6.8). CONCLUSION: There was significant delay of ART initiation among referred PLHIV within 5 years after the rollout of test and treat guidelines in Uganda. Health system challenges in the continuity of HIV care services negatively affects timely ART initiation among referred PLHIV in Uganda.

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.

Improved hypertension control at six months using an adapted WHO HEARTS-based implementation strategy at a large urban HIV clinic in Uganda.

OBJECTIVES: To adapt a World Health Organization HEARTS-based implementation strategy for hypertension (HTN) control at a large urban HIV clinic in Uganda and determine six-month HTN and HIV outcomes among a cohort of adult persons living with HIV (PLHIV). METHODS: Our implementation strategy included six elements: health education, medication adherence, and lifestyle counseling; routine HTN screening; task shifting of HTN treatment; evidence-based HTN treatment protocol; consistent supply of HTN medicines free to patients; and inclusion of HTN-specific monitoring and evaluation tools. We conducted a pre-post study from October 2019 to March 2020 to determine the effect of this strategy on HTN and HIV outcomes at baseline and six months. Our cohort comprised adult PLHIV diagnosed with HTN who made at least one clinic visit within two months prior to study onset. FINDINGS: We enrolled 1,015 hypertensive PLHIV. The mean age was 50.1 ± 9.5 years and 62.6% were female. HTN outcomes improved between baseline and six months: mean systolic BP (154.3 ± 20.0 to 132.3 ± 13.8 mmHg, p < 0.001); mean diastolic BP (97.7 ± 13.1 to 85.3 ± 9.5 mmHg, p < 0.001) and proportion of patients with controlled HTN (9.3% to 74.1%, p < 0.001). The HTN care cascade also improved: treatment initiation (13.4% to 100%), retention in care (16.2% to 98.5%), monitoring (16.2% to 98.5%), and BP control among those initiated on HTN treatment (2.2% to 75.2%). HIV cascade steps remained high (> 95% at baseline and six months) and viral suppression was unchanged (98.7% to 99.2%, p = 0.712). Taking ART for more than two years and HIV viral suppression were independent predictors of HTN control at six months. CONCLUSIONS: A HEARTS-based implementation strategy at a large, urban HIV center facilitates integration of HTN and HIV care and improves HTN outcomes while sustaining HIV control. Further implementation research is needed to study HTN/HIV integration in varied clinical settings among diverse populations.

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.

Adoption of evidence-informed guidelines in prescribing protease inhibitors for HIV-Tuberculosis co-infected patients on rifampicin and effects on HIV treatment outcomes in Uganda.

BACKGROUND: We aimed to determine how emerging evidence over the past decade informed how Ugandan HIV clinicians prescribed protease inhibitors (PIs) in HIV patients on rifampicin-based tuberculosis (TB) treatment and how this affected HIV treatment outcomes. METHODS: We reviewed clinical records of HIV patients aged 13 years and above, treated with rifampicin-based TB treatment while on PIs between1st-January -2013 and 30th-September-2018 from twelve public HIV clinics in Uganda. Appropriate PI prescription during rifampicin-based TB treatment was defined as; prescribing doubled dose lopinavir/ritonavir- (LPV/r 800/200 mg twice daily) and inappropriate PI prescription as prescribing standard dose LPV/r or atazanavir/ritonavir (ATV/r). RESULTS: Of the 602 patients who were on both PIs and rifampicin, 103 patients (17.1% (95% CI: 14.3-20.34)) received an appropriate PI prescription. There were no significant differences in the two-year mortality (4.8 vs. 5.7%, P = 0.318), loss to follow up (23.8 vs. 18.9%, P = 0.318) and one-year post TB treatment virologic failure rates (31.6 vs. 30.7%, P = 0.471) between patients that had an appropriate PI prescription and those that did not. However, more patients on double dose LPV/r had missed anti-retroviral therapy (ART) days (35.9 vs 21%, P = 0.001). CONCLUSION: We conclude that despite availability of clinical evidence, double dosing LPV/r in patients receiving rifampicin-based TB treatment is low in Uganda's public HIV clinics but this does not seem to affect patient survival and viral suppression.

An assessment of implementation science research capacity in Uganda.

BACKGROUND: In Uganda and other resource-poor countries, relevant research findings face a tortuous path to translation into policy and routine practice. Implementation science (ImSc) research could facilitate faster translation. Presently it is unclear what ImSc research capacity and possible training needs exist among Ugandan researchers. To assess both components, we interviewed potential trainees in Kampala, Uganda. METHODS: We used a cross-sectional design to survey potential ImSc trainees who had some research training and involvement in generating or utilizing research. Using a questionnaire, we documented eligibility for ImSc training, knowledge and interest in training, existing self-assessed confidence in initiating clinical research (SCICR) and self-assessed confidence in initiating ImSc research (SCIIR), availability for training and preferred modes of training. We developed scores from the Likert scales and used descriptive statistics, logistic regression and ordinal logistic regression to evaluate predictors of SCIIR. RESULTS: Between November 2016 and April 2017, we interviewed 190 participants; 60% were men, with a median age of 37 years. Among participants, 33% comprised faculty, 37% were graduate students and 30% were project staff. The majority of respondents knew about ImSc (73%) and were research-trained (80%). Only 9% reported any ImSc-related training. Previous ImSc training was associated with higher odds of a SCIIR score ≥ 75th percentile. Previous ImSc training compared to not having any training was associated with higher odds of reporting abilities in behaviour change theory integration (OR: 3.3, 95% CI: 1.3-8.5, p = 0.01) and framework use in intervention design and implementation (OR: 2.9, 95% CI: 1.1-7.4, p = 0.03), accounting for age, sex and current employment. In addition, 53% of participants preferred in-person (face-to-face) short ImSc courses compared to a year-long training, while 33% preferred online courses. Participants reported median availability of 6 hours per week (IQR: 4, 10) for training. CONCLUSION: Most participants had some understanding of ImSc research, had research training and were interested in ImSc training. Those with previous ImSc training had better skills and SCIIR, compared to those without previous training. A hybrid approach with modular face-to-face training and online sessions would suit the preferences of most potential trainees.

Yield and Efficiency of Novel Intensified Tuberculosis Case-Finding Algorithms for People Living with HIV.

RATIONALE: The recommended tuberculosis (TB) intensified case finding (ICF) algorithm for people living with HIV (symptom-based screening followed by Xpert MTB/RIF [Xpert] testing) is insufficiently sensitive and results in unnecessary Xpert testing. OBJECTIVES: To evaluate whether novel ICF algorithms combining C-reactive protein (CRP)-based screening with urine Determine TB-LAM (TB-LAM), sputum Xpert, and/or sputum culture could improve ICF yield and efficiency. METHODS: We compared the yield and efficiency of novel ICF algorithms inclusive of point-of-care CRP-based TB screening and confirmatory testing with urine TB-LAM (if CD4 count ≤100 cells/µl), sputum Xpert, and/or a single sputum culture among consecutive people living with HIV with CD4 counts less than or equal to 350 cells/µl initiating antiretroviral therapy in Uganda. MEASUREMENTS AND MAIN RESULTS: Of 1,245 people living with HIV, 203 (16%) had culture-confirmed TB including 101 (49%) patients with CD4 counts less than or equal to 100 cells/µl. Compared with the current ICF algorithm, point-of-care CRP-based TB screening followed by Xpert testing had similar yield (56% [95% confidence interval, 49-63] vs. 59% [95% confidence interval, 51-65]) but consumed less than half as many Xpert assays per TB case detected (9 vs. 4). Addition of TB-LAM did not significantly increase diagnostic yield relative to the current ICF algorithm but provided same-day diagnosis for 26% of TB patients with advanced HIV. Addition of a single culture to TB-LAM and Xpert substantially improved ICF yield, identifying 78% of all TB cases. CONCLUSIONS: Point-of-care CRP-based screening can improve ICF efficiency among people living with HIV. Addition of TB-LAM and a single culture to Xpert confirmatory testing could enable HIV programs to increase the speed of TB diagnosis and ICF yield.

A Novel, 5-Transcript, Whole-blood Gene-expression Signature for Tuberculosis Screening Among People Living With Human Immunodeficiency Virus.

BACKGROUND: Gene-expression profiles have been reported to distinguish between patients with and without active tuberculosis (TB), but no prior study has been conducted in the context of TB screening. METHODS: We included all the patients (n = 40) with culture-confirmed TB and time-matched controls (n = 80) enrolled between July 2013 and April 2015 in a TB screening study among people living with human immunodeficiency virus (PLHIV) in Kampala, Uganda. We randomly split the patients into training (n = 80) and test (n = 40) datasets. We used the training dataset to derive candidate signatures that consisted of 1 to 5 differentially-expressed transcripts (P ≤ .10) and compared the performance of our candidate signatures with 4 published TB gene-expression signatures, both on the independent test dataset and in 2 external datasets. RESULTS: We identified a novel, 5-transcript signature that met the accuracy thresholds recommended for a TB screening test. On the independent test dataset, our signature had an area under the curve (AUC) of 0.87 (95% confidence interval [CI] 0.72-0.98), with sensitivity of 94% and specificity of 75%. None of the 4 published TB signatures achieved desired accuracy thresholds. Our novel signature performed well in external datasets from both high (AUC 0.81, 95% CI 0.74-0.88) and low (0.81, 95% CI 0.77-0.85) TB burden settings. CONCLUSIONS: We identified the first gene-expression signature for TB screening. Our signature has the potential to be translated into a point-of-care test to facilitate systematic TB screening among PLHIV and other high-risk populations.

Loss to follow-up and associated factors among adult people living with HIV at public health facilities in Wakiso district, Uganda: a retrospective cohort study.

BACKGROUND: Loss to follow-up (LTFU) from care among people living with HIV (PLHIV) is thought to be more common in the public setting compared to the private health care. It is anticipated that the problem may become worse with the current "test and treat" policy in Uganda due to the likely increases in patient loads and its attendant pressure on health care providers to support patient counseling. This study determined the incidence and factors associated with LTFU from HIV care among adult PLHIV in public health facilities in Wakiso district, Uganda. METHODS: This was a retrospective cohort study that involved the review of 646 records of patients initiated on antiretroviral therapy (ART) between January 1st, 2015 and December 31st, 2017 at 13 randomly selected public health facilities in Wakiso district. The cox proportional hazards regression was used to determine the factors associated with LTFU. The results were supported by sequential in-depth and key informant interviews to explore reasons for LTFU. RESULTS: Of the 646 patients enrolled, 391 were female (60.5%), 282 were below 30 years (43.6%) and 207 were married (50.1%). A total of 216 patients (33.4%) had no documented outcomes and were considered LTFU. The incidence of LTFU was 21 per 1000 person months (95% confidence interval (CI): 18-25 per 1000 person months). Factors associated with LTFU included having normal weight compared to underweight (adjusted hazard ratio (aHR) 0.64, 95% CI: 0.45-0.90, p = 0.011), receiving HIV care from hospitals compared to lower level facilities (aHR 0.22, 95% CI: 0.12-0.41, p < 0.001), and no telephone contact compared to those with a telephone contact (aHR 2.16, 95% CI: 1.33-3.51, p = 0.002). Stigmatization and long waiting times were the prominent reasons for LTFU reported from the in-depth and key informant interviews. CONCLUSIONS: The incidence of LTFU in public health facilities in Uganda is quite high and is associated with being underweight, not having a telephone contact to receive reminders and receiving care at lower level facilities. Early diagnosis, routine use of patient address locator forms and improved quality of HIV care at lower level health facilities may reduce LTFU among PLHIV.

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.

Prevalence, Associated Factors, Barriers and Facilitators for Oral HIV Self-Testing among Partners of Pregnant Women Attending Antenatal Care Clinics in Wakiso, Uganda.

Background: Oral HIV self-testing (HIVST) among men is relatively low and still inadequate in Sub-Saharan Africa. Delivering HIVST kits by pregnant women attending antenatal care to their partners is a promising strategy for increasing HIV testing among men. However, even amidst the interventions, most men do not know their HIV status. This study, aimed to determine the proportion of partners who received and used oral HIVST kits delivered by pregnant women, associated factors, barriers, and facilitators for uptake among partners. Methods: We conducted an exploratory sequential mixed methods study among 380 sampled partners. Lists of partners in the HIVST log books whose women picked an HIVST kit were obtained and systematic random sampling was done to obtain participants. 14 male partners were purposively selected for in-depth interviews (IDIs) to identify barriers and facilitators. We used modified poison regression to determine the association between oral HIVST and independent variables. We used an inductive analysis for the qualitative analysis. Results: Out of 380 participants, 260(68.4%) received an oral HIVST kit from their pregnant women, and 215(82.7%) used the kit for HIVST. Oral HIVST was associated with; Information Education and Communication (CPR = 1.64, 95%CI 1.48-1.82), being reached at home (CPR = 1.04, 95%CI 1.01-1.08), and being aware of the woman's HIV status (CPR = 1.04, 95%CI 0.99-1.09). In-depth results identified barriers to uptake as, lack of trust in the HIVST kit results, fear of test outcome in the presence of the partner and inclination that the HIV status of their women is the same as theirs, and facilitators included convenience, ease to use, prior awareness of their HIV status, and fear of relationship consequences and breakup. Conclusion: Delivery of oral HIVST kits to men through pregnant women reached a high number of men and achieved a high uptake. Accessing information, education, communication and convenience nature were the major reasons for uptake among men who received the Oral HIVST kit as trust issues of the kit affected use among partners. Scaling up the delivery of oral HIVST kits at all departments of the hospital through women seeking health services is paramount to support HIV screening among men to reach the UNAIDS 95 strategy.

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.

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.

Low COVID-19 vaccine uptake in people living with HIV and those with hypertension and diabetes without HIV at Mbarara and Masaka regional referral hospitals: A cross-sectional survey.

Chronic diseases such as HIV, hypertension, and diabetes increase the risk of severe coronavirus disease 2019 (COVID-19) and death. Thus, COVID-19 vaccine uptake data among these priority populations are needed to inform immunization programs. We assessed COVID-19 vaccine uptake among people living with HIV (PLWH) and those with hypertension/diabetes without HIV (PWoH) in Southwestern and Southcentral Uganda and determined factors influencing vaccination. We conducted a cross-sectional study from January to April 2023. We enrolled a random sample of participants aged 18 years and older seeking HIV, hypertension, or diabetes care at two regional referral hospitals (RRHs) in Mbarara and Masaka in Uganda. Using vaccination records abstraction and interviewer-administered questionnaires, we collected data on COVID-19 vaccine uptake, sociodemographic data, and reasons for non-uptake in unvaccinated persons. We compared COVID-19 vaccination uptake between PLWH and PWoH and applied modified Poisson regression to determine sociodemographic factors associated with vaccine uptake. The reasons for non-vaccine uptake were presented as percentages. Of the 1,376 enrolled participants, 65.6% were fully vaccinated against COVID-19. Vaccination coverage was 65% among PWLH versus 67% among PWoH. Higher education attainment and older age were associated with COVID vaccination. Participants with secondary education and those aged ≥50 years achieved >70% coverage. Fear of side effects was the most cited reason (67%) for non-vaccination among 330 unvaccinated participants, followed by vaccine mistrust (24.5%). People with chronic diseases in Southwestern Uganda had slightly lower than 70% COVID-19 vaccine coverage as recommended by WHO. Higher educational attainment and older age were linked to increased vaccine uptake. However, mistrust and fear of vaccine side effects were the main reasons for non-vaccination. To increase COVID-19 vaccine uptake, programs must reach those with lower educational attainment and younger age groups, and address the fear of vaccine side effects and mistrust among persons with underlying diseases in Uganda.

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.