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ItemEstimating the effect of pretreatment loss to follow up on TB associated mortality at public health facilities in Uganda(Plos one, 2020)Introduction Tuberculosis (TB) mortality estimates derived only from cohorts of patients initiated on TB treatment do not consider outcomes of patients with pretreatment loss to follow-up (LFU). We aimed to assess the effect of pretreatment LFU on TB-associated mortality in the six months following TB diagnosis at public health facilities in Uganda. Methods At ten public health facilities, we retrospectively reviewed treatment data for all patients with a positive Xpert®MTB/RIF test result from January to June 2018. Pretreatment LFU was defined as not initiating TB treatment within two weeks of a positive test. We traced patients with pretreatment LFU to ascertain their vital status. We performed Kaplan Meier survival analysis to compare the cumulative incidence of mortality, six months after diagnosis among patients who did and did not experience pretreatment LFU. We also determined the health facility level estimates of TB associated mortality before and after incorporating deaths prior to treatment initiation among patients who experienced pretreatment LFU. Results Of 510 patients with positive test, 100 (19.6%) experienced pretreatment LFU. Of these, we ascertained the vital status of 49 patients. In the six months following TB diagnosis, mortality was higher among patients who experienced pretreatment LFU 48.1/1000py vs 22.9/1000py. Hazard ratio [HR] 3.18, 95% confidence interval [CI] (1.61–6.30). After incorporating deaths prior to treatment initation among patients who experienced pretreatment LFU, health facility level estimates of TB associated mortality increased from 8.4% (95% CI 6.1%-11.6%) to 10.2% (95% CI 7.7%-13.4%). Conclusion Patients with confirmed TB who experience pretreatment LFU have high mortality within the first six months. Efforts should be made to prioritise linkage to treatment for this group of patients. Deaths that occur prior to treatment initation should be included when reporting TB mortality in order to more accurately reflect the health impact of TB.
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ItemEfficacy of HIV interventions in African fishing communities: A systematic review and qualitative synthesis(Elsevier, 2020)Objectives: This systematic review aims to qualitatively synthesize existing evidence on the efficacy of HIV interventions in African fishing communities. Methods: Five databases (NCBI PubMed, EMBASE, Web of Science Core Collection, The Cochrane Library, and CABI Global Health Database) were searched in March 2019 for eligible studies. All peer-reviewed papers with a defined HIV intervention explicitly mentioning African fishing communities were included. Outcomes included any measure of the efficacy of HIV interventions. Results: Of 22,289 search results, data was extracted from 25 eligible studies that passed critical appraisal; seven involved HIV prevention, six HIV testing and counseling, three treatment, and nine combinations of more than one intervention. Findings include a high coverage of safe male circumcision (SMC) but low condom use among fisher folk, and a preference for PrEP over other HIV prevention services. Uptake of HIV testing and ART coverage are below levels required to reach UNAIDS 90-90-90 targets, and there is a high demand for ART and HIV self-testing kits. Conclusions: Greater provision of services to combat HIV, specifically amongst fishing communities, is required; there is limited information on retaining fisher folk in care and achieving an undetectable viral load. Interventions tailored to individual fishing populations, offered in parallel to education or counseling services are likely to be most effective. Use of innovations, including mobile health and medical drones, could assist these hard-to-reach populations. Our findings will inform future HIV service provision in fishing communities.
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ItemIncreased levels of caspase-1 and IL-1β among adults with persistent immune activation after 12 years of suppressive antiretroviral therapy in the Infectious Diseases Institute HIV Treatment Cohort(Oxford Academic, 2023)Background We sought evidence of activated pyroptosis and the inflammasome pathways among human immunodeficiency virus (HIV)–infected adults after 12 years of suppressive antiretroviral therapy (ART) and persistent immune activation in the Infectious Diseases Institute HIV treatment cohort in Uganda. Methods In a cross-sectional study, using peripheral blood mononuclear cells of HIV-infected individuals with high and low immune activation (CD4/CD8+CD38+HLA-DR+ cells) relative to HIV-negative reference group, caspase-1 expression was measured using flow cytometry and plasma interleukin 18 and interleukin 1β (IL-1β) levels using enzyme-linked immunosorbent assay. Results There was higher expression of caspase-1 by CD4 T cells of ART-treated individuals with high immune activation relative to those with lower immune activation (P = .04). Similarly, plasma levels of IL-1β were higher among ART-treated individuals with high immune activation levels relative to those with low immune activation levels (P = .009). We observed a low positive correlation between caspase-1 expression by CD4/CD8 T cells and immune activation levels (r = 0.497 and r = 0.329, respectively). Conclusions Caspase-1 and IL-1β were high among individuals with high immune activation despite 12 years of suppressive ART. There is a need to further understand the role of persistent abortive infection and the latent HIV reservoir characteristics as drivers of persistent activation and inflammation and to subsequently intervene to prevent the complications of chronic immune activation during long-term ART.
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ItemImpact of differentiated service delivery models on quality of life among people living with HIV in Uganda – A quasi-experimental study(Research Square, 2024-12)Background Differentiated service delivery (DSD) models in resource-limited settings have reduced strain on health services and improved client experience, retention and viral suppression, but little is known about the impact of HIV DSD models on quality of life (QoL), which is essential for optimizing person-centered care. This study assessed the impact of DSD models on QoL, loss to follow-up (LTFU), and mortality among persons living with HIV (PLHIV) on ART over time at a large urban HIV clinic in Uganda. Methods We analyzed records of 1,000 PLHIV who had been on ART for 10 years and followed up for eight years, starting in 2014 or 2015 at the Infectious Diseases Institute clinic in Kampala, Uganda. The primary outcome, QoL, was assessed using an adapted Medical Outcomes Study (MOS-HIV) tool. Secondary outcomes included sustained viral suppression (< 200 copies/mL), all-cause mortality, and loss to follow-up or LTFU (missing clinic visits for ≥ 3 months). Outcomes were compared across three DSD models—fast-track drug refill (FTDR), facility-based groups (FBG), and a composite model combining FTDR and FBG against the facility-based individual management (FBIM), the standard of care (SOC). Inverse probability treatment weighting was used to achieve comparability in measured covariates across the DSD models followed by mixed effects modeling. Robustness of results was checked using G-computation analysis. Results Of 1,000 records for PLHIV, 980 were analyzed. 62% were female and 95% virally suppressed at baseline. After eight years of follow-up, participants on DSD models had higher QoL (90.4% vs 89.1%; weighted mean ratio 3.66, 95% CI 2.10–6.37, p-value < 0.001), better sustained viral suppression, lower mortality, and reduced LTFU rates compared to SOC. Conclusion These findings support the broader adoption of DSD models in delivering ART across HIV programs to enhance the QoL and clinical outcomes among PLHIV.
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ItemHealth research mentorship in low-income and middle-income countries: a global qualitative evidence synthesis of data from a crowdsourcing open call and scoping review(BMJ, 2024)Introduction: Research mentorship is critical for advancing science, but there are few practical strategies for cultivating mentorship in health research resource-limited settings. WHO/TDR Global commissioned a group to develop a practical guide on research mentorship. This global qualitative evidence synthesis included data from a crowdsourcing open call and scoping review to identify and propose strategies to enhance research mentorship in low/middle-income country (LMIC) institutions. Methods: The crowdsourcing open call used methods recommended by WHO/TDR and solicited descriptions of strategies to enhance research mentorship in LMICs. The scoping review used the Cochrane Handbook and predefined the approach in a protocol. We extracted studies focused on enhancing health research mentorship in LMICs. Textual data describing research mentorship strategies from the open call and studies from the scoping review were coded into themes. The quality of evidence supporting themes was assessed using the Confidence in the Evidence from Reviews of Qualitative research approach. Results: The open call solicited 46 practical strategies and the scoping review identified 77 studies. We identified the following strategies to enhance research mentorship: recognising mentorship as an institutional responsibility that should be provided and expected from all team members (8 strategies, 15 studies; moderate confidence); leveraging existing research and training resources to enhance research mentorship (15 strategies, 49 studies; moderate confidence); digital tools to match mentors and mentees and sustain mentorship relations over time (14 strategies, 11 studies; low confidence); nurturing a culture of generosity so that people who receive mentorship then become mentors to others (7 strategies, 7 studies; low confidence); peer mentorship defined as informal and formal support from one researcher to another who is at a similar career stage (16 strategies, 12 studies; low confidence). Interpretation: Research mentorship is a collective institutional responsibility, and it can be strengthened in resource-limited institutions by leveraging already existing resources. The evidence from the crowdsourcing open call and scoping review informed a WHO/TDR practical guide. There is a need for more formal research mentorship programmes in LMIC institutions.