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Background HIV disclosure is vital in HIV management. Community Health Workers (CHW) were reported to support partner disclosure among HIV affected heterosexual partners with disclosure difficulties. However, time to disclosure attributed to use of CHW led disclosure support mechanism was not documented. This study compared the incidence of sexual partner disclosure among adults living with HIV (ALHIV) with CHW support and those without in the greater Luwero region, Uganda. Methods We conducted a quasi-experimental study with two arms allocated by geographically determined clusters and adjusted for between-group differences; among ALHIV in the greater Luwero region of Uganda who had never disclosed to their current primary sexual partners. We allocated study clusters to either a CHW-led intervention or control arm. In both arms, we consecutively recruited participants; those in the intervention arm received CHW disclosure support in addition to routine care. The overall follow-up was six months, and the primary outcome was disclosure to the partner. We used survival analysis with proportional hazard ratios to determine the time to partner disclosure in both arms. Results A total of 245 participants were enrolled, and 230 (93.9%) completed the study; of these, 112 (48.7%) were in the intervention and 118 (51.3%) in the control arm. The mean age was 31 ± 8 years with a range of 18 to 55 years; the majority were females, 176 (76.5%). The cumulative incidence of disclosure was higher in the intervention arm, 8.76 [95% CI: 7.20–10.67] per 1,000 person-days versus 5.15 [95%CI: 4.85–6.48] per 1,000 person-days in the control arm, log-rank test, X2 = 12.93, P  < 0.001. Male gender, aHR = 1.82, tertiary education, aHR = 1.51, and relationship duration of > six months, aHR = 1.19 predicted disclosure. Prior disclosure to a relative, aHR = 0.55, and having more than one sexual partner in the past three months, aHR = 0.74, predicted non-disclosure. Conclusion CHW-led support mechanism increased the rate of sexual partner disclosure among ALHIV with disclosure difficulties. Therefore, to achieve the global targets of ending HIV, near location CHW-led disclosure support mechanism may be used to hasten HIV disclosure in rural settings.

Background Tuberculosis (TB) is a significant public health problem that causes substantial morbidity and mortality. Current first-line anti-TB chemotherapy, although very effective, has limitations including long-treatment duration with a possibility of non-adherence, drug interactions, and toxicities. Dose escalation of rifampicin, an important drug within the regimen, has been proposed as a potential route to higher treatment efficacy with shorter duration and some studies have suggested that dose escalation is safe; however, these have almost entirely been conducted among human immunodeficiency (HIV)-negative TB patients. TB-HIV co-infected patients on antiretroviral therapy (ART) are at increased risk of drug-drug interactions and drug-related toxicities. This study aims to determine the safety of higher doses of rifampicin and its effect on the pharmacokinetics of efavirenz (EFV) and dolutegravir (DTG) in TB-HIV co-infected patients. Methods This study is a randomized, open-label, phase IIb clinical trial among TB-HIV infected adult outpatients attending an HIV clinic in Kampala, Uganda. Patients newly diagnosed with TB will be randomized to either standard-dose or high-dose rifampicin (35 mg/kg) alongside standard TB treatment. ART-naïve patients will be randomly assigned to first-line ART regimens (DTG or EFV). Those who are already on ART (DTG or EFV) at enrollment will be continued on the same ART regimen but with dose adjustment of DTG to twice daily dosing. Participants will be followed every 2 weeks with assessment for toxicities at each visit and measurement of drug concentrations at week 6. At the end of intensive-phase therapy (8 weeks), all participants will be initiated on continuation-phase treatment using standard-dose rifampicin and isoniazid. Discussion This study should avail us with evidence about the effect of higher doses of rifampicin on the pharmacokinetics of EFV and DTG among TB-HIV co-infected patients. The trial should also help us to understand safety concerns of high-dose rifampicin among this vulnerable cohort. Trial registration ClinicalTrials.gov , ID: NCT03982277 . Registered retrospectively on 11 June 2019.

Background HIV status disclosure among sexual partners is vital in HIV management. Community health workers (CHW) support HIV disclosure among adults living with HIV (ALHIV) in sexual relationships with disclosure difficulties. However, experiences and challenges of using CHW-led disclosure support mechanism were not documented. This study explored experiences and challenges involved in using CHW-led disclosure support mechanism among ALHIV in heterosexual relationships in the rural Uganda. Methods This was a phenomenological qualitative study involving in-depth interviews among CHWs and ALHIV with HIV disclosure difficulties to sexual partners in greater Luwero region, Uganda. We conducted 27 interviews among purposively selected CHWs and participants who had participated in the CHW-led disclosure support mechanism. Interviews were conducted until saturation was reached; and analysis was done using inductive and deductive content analysis in Atlas. Results All respondents viewed HIV disclosure as an important strategy in HIV management. Provision of adequate counseling and support to those intending to disclose was instrumental for successful disclosure. However, fear of the negative disclosure outcomes was viewed as a barrier to disclosure. The CHWs were viewed as having an added advantage in supporting disclosure as opposed to the routine disclosure counseling. However, HIV disclosure using CHW-led support mechanism would be limited by possible bleach of client’s confidentiality. Therefore, respondents thought that appropriate selection of CHWs would improve their trust in the community. Additionally, providing CHWs with adequate training and facilitation during the disclosure support mechanism was viewed to improve their work. Conclusion Community health workers were viewed as being more supportive in HIV disclosure among ALHIV with disclosure difficulties to sexual partners compared to routine facility based disclosure counseling. Therefore, near location CHW-led disclosure mechanism was acceptable and useful in supporting HIV disclosure among HIV-affected sexual partners in rural settings.

Background Malaria prevention during pregnancy significantly minimizes maternal–fetal adverse events. However, optimal uptake of malaria preventive therapy in pregnancy (MPTp) remains a major challenge for both women living with HIV and those without. In Uganda, suboptimal uptake of MPTp is primarily due to inadequate knowledge among women. This study aimed to develop and assess the feasibility and acceptability of an educational video to improve knowledge of MPTp among pregnant women living with and without HIV. Methods This study describes the second phase of a mixed methods study conducted among pregnant women (living with and without HIV) and midwives from a public antenatal care clinic in Kampala, Uganda. The study was conducted from October 2022 to Jan 2024, and the first phase involved qualitative data collection from pregnant women, health workers, and Ministry of Health officials to develop a video-based intervention to enhance uptake of MPTp. The second phase involved administration of the developed intervention to a group of purposively selected pregnant women living with and without HIV. Questionnaires, focus group discussions, and interviews were used to collect data among women and midwives, and to assess feasibility and acceptability of the intervention. Quantitative data were summarized using descriptive statistics and analysed using different scales of measurement including the modified system usability scale and the Evidence-based Practice and Attitude Scale (EBPAS), which assessed acceptability among pregnant women and midwives, respectively. The qualitative data were coded and analysed using inductive and deductive thematic methods in Atlas ti.8. Results A total of 45 women and six midwives were enrolled in the current study phase. The mean age (± standard deviation, SD) of the women was 26 ± 6 years, and the median gestational age (interquartile range, IQR) was 24 (20–32) weeks, and less than half (42%, n = 19) were living with HIV. On the system usability scale, most women (91%, n = 41) rated the intervention as good or excellent, and most (93%, n = 42) were satisfied or very satisfied with the intervention. On the EBPAS, midwives perceived the intervention as reliable with Cronbach’s alpha of 0.74, and all midwives found the intervention appropriate and feasible in their facility. All women comprehended and highly accepted the intervention. Conclusion The video-based intervention for uptake of MPTp was found acceptable among women and midwives and was feasible and appropriate to a public health facility. Future studies would test the effectiveness of the intervention in improving knowledge and uptake of MPTp.

Background Malaria in pregnancy remains a major global public health problem. Intermittent prophylaxis treatment of malaria in pregnancy with Sulphadoxine-pyrimethamine and co-trimoxazole is efficacious for prevention of malaria in pregnancy HIV negative and positive women, respectively. However, uptake of the recommended doses of therapies has remained suboptimal in Uganda, majorly due to inadequate knowledge among pregnant women. Therefore, this study aimed to explore attitudes and perceptions towards developing an educational video for malaria preventive therapy. Methods We conducted an exploratory study with qualitative methods among pregnant women attending antenatal care at Kisenyi Health Center IV (KHCIV), health workers from KHCIV, and officials from the Ministry of Health. The study was conducted at KHCIV from October 2022 to March 2023. Focus group discussions (FGD) were conducted among purposively selected pregnant women and key informant interviews (KII) among health workers and Ministry of Health officials. Data were analyzed using inductive and deductive thematic methods in atlas ti.8. Results A total of five FGDs comprising of 7–10 pregnant women were conducted; and KIIs were conducted among four mid-wives, two obstetricians, and two Ministry of Health officials. Generally, all respondents mentioned a need for interventions to improve malaria preventive knowledge among pregnant women; were positive about developing an educative video for malaria preventive therapy in pregnancy; and suggested a short, concise, and edutaining video focusing both the benefits of taking and risks of not taking malaria preventive therapy. They proposed that women may be encouraged to view the video as soon as they conceive and throughout the pregnancy. It also was suggested that the video may be viewed on television sets in maternal and reproductive health clinics and homes, and on smart phones. Conclusion Pregnant women, health workers, and Ministry of Health officials were positive about the development of a short edutaining video on malaria preventive therapy that focuses on both benefits of taking and risks of not taking the malaria preventive therapy in pregnancy. This information guided the video development and therefore, in the development of health educative videos, client and stakeholder inputs may always be solicited.

IntroductionTuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings.MethodsThis is an observational cohort study with a nested case–control study. We enrolled consecutive patients who had been initiated on TPT using the 3HP regimen. These are followed up biweekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2, AADAC and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes.AnalysisThe safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. χ2 tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modelling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.Ethics and disseminationEthical approval of this study inclusive of all the appropriate documents was obtained from the Infectious Diseases Institute Research and Ethics Committee and the Uganda National Council of Science and Technology. The study adheres to legal, ethical and Good Clinical Practice (GCP) guidelines. Deidentified genotype data from 300 patients will be shared after publication. The protocol and phenotype data will be publicly accessible. Abstracts will be submitted to conferences, and a manuscript will be published poststudy.

WHO recommends a 2-month optimal duration for new drug regimens for rifampicin-susceptible tuberculosis. We aimed to investigate the efficacy and safety of the 8-week regimens that were assessed as part of the TRUNCATE management strategy of the TRUNCATE-TB trial. TRUNCATE-TB was a multi-arm, multi-stage, open-label, randomised controlled trial in which participants aged 18–65 years with rifampicin-susceptible pulmonary tuberculosis were randomly assigned via a web-based system, using permuted blocks, to 24-week standard treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol) or the TRUNCATE management strategy comprising initial 8-week treatment, then post-treatment monitoring and re-treatment where needed. The four 8-week regimens comprised five drugs, modified from standard treatment: high-dose rifampicin and linezolid, or high-dose rifampicin and clofazimine, or bedaquiline and linezolid, all given with isoniazid, pyrazinamide, and ethambutol; and rifapentine, linezolid, and levofloxacin, given with isoniazid and pyrazinamide. Here, we report the efficacy (proportion with unfavourable outcome; and difference from standard treatment, assessed via Bayesian methods) and safety of the 8-week regimens, assessed in the intention-to-treat population. This prespecified exploratory analysis is distinct from the previously reported 96-week outcome of the strategy in which the regimens were deployed. This trial is registered with ClinicalTrials.gov (NCT03474198). Between March 21, 2018, and March 26, 2020, 675 participants (674 in the intention-to-treat population) were enrolled and randomly assigned to the standard treatment group or one of the four 8-week regimen groups. Two 8-week regimens progressed to full enrolment. An unfavourable outcome (mainly relapse) occurred in seven (4%) of 181 participants on standard treatment; 46 (25%) of 184 on the high-dose rifampicin and linezolid-containing regimen (adjusted difference 21·0%, 95% Bayesian credible interval [BCI] 14·3–28·1); and 26 (14%) of 189 on the bedaquiline and linezolid-containing regimen (adjusted difference 9·3% [4·3–14·9]). Grade 3–4 adverse events occurred in 24 (14%) of 181 participants on standard treatment, 20 (11%) of 184 on the rifampicin-linezolid regimen, and 22 (12%) of 189 on the bedaquiline-linezolid regimen. Efficacy was worse with 8-week regimens, although the difference from standard treatment varied between regimens. Even the best 8-week regimen (bedaquiline-linezolid) should only be used as part of a management strategy involving post-treatment monitoring and re-treatment if necessary. Singapore National Medical Research Council; UK Department of Health and Social Care; UK Foreign, Commonwealth, and Development Office; UK Medical Research Council; Wellcome Trust; and UK Research and Innovation Medical Research Council.

Background Pediatric tuberculosis is a major global public health challenge, with reliable diagnosis being a main obstacle to identifying and treating affected children. New and improved diagnostics, ideally on non-sputum samples, are urgently required, especially in the most vulnerable group of children under five years of age. Studies to date have been limited by small sample sizes and few bacteriologically-confirmed cases. Here, we describe the study protocol of the NIH-funded NOD-pedFEND study, which will be one of the largest diagnostic studies to date of children at greatest risk of tuberculosis. Methods In this prospective observational cohort study, we aim to evaluate existing and novel diagnostic assays, including pathogen- and host-based tests and combinations of tests. A consecutive cohort of children under five years of age with signs and symptoms of tuberculosis is enrolled in Uganda and Peru. All children undergo an extensive baseline workup with signs- and symptoms recording, microbiological reference tests, chest X-ray and tuberculin skin test for rigorous classification according to internationally recognized microbiological, composite reference and strict standards. An array of samples is collected for investigational tests. Follow-up visits are conducted at 2 weeks, 2 months and 6 months. A small cohort of healthy controls is enrolled to evaluate the specificity of selected diagnostics. The study has been approved by the relevant institutional review boards. Discussion With this large cohort study of children under five years of age, we aim to make an important contribution to the evaluation of new diagnostics for pediatric tuberculosis. By establishing a comprehensive biorepository, the study will also enable the assessment of novel tests as they become available during and after the study.