Objective: Although international guidelines recommend initiating antiretroviral therapy (ART) when a patient's CD4 cell count is ≤350 cells/μL, most patients in resource-limited settings present with much lower CD4 cell counts. The lowest level that their CD4 cell count reaches, the nadir, may have long-term consequences in terms of mortality. We examined this health state in a large cohort of HIV+ patients in Uganda.
Design: This was an observational study of HIV patients in Uganda aged 14 years or older, who were enrolled in 10 major clinics across Uganda.
Methods: We assessed the CD4 nadir of patients, using their CD4 cell count at initiation of ART, stratified into categories (,50, 50-99, 100-149, 150-249, 250+ cells/μL). We constructed Kaplan-Meier curves to assess the differences in survivorship for patients left-censored at 1 year and 2 years after treatment initiation. We used Cox proportional hazards regression to model the associations between CD4 nadir and mortality. We adjusted mortality for loss-to-follow-up.
Results: Of 22,315 patients, 20,129 patients had greater than 1 year of treatment follow-up. Among these patients, 327 (1.6%) died and 444 (2.2%) were lost to follow-up. After left-censoring at one year, relative to lowest CD4 strata, patients with higher CD4 counts had significantly lower rates of mortality (CD4 150-249, hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.45-0.82, P = 0.001; 250+, HR 0.66, 95% CI, 0.44-1.00, P = -0.05). Male sex, older age, and duration of time on ART were independently associated with mortality. When left-censoring at 2 years, CD4 nadir was no longer statistically significantly associated with mortality.
Conclusion: After surviving for 1 year on ART, a CD4 nadir was strongly predictive of longer-term mortality among patients in Uganda. This should argue for efforts to increase engagement with patients to ensure a higher CD4 nadir at initiation of treatment.
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http://dx.doi.org/10.2147/HIV.S35374 | DOI Listing |
J Hematop
January 2025
Cleveland Clinic Florida, Weston, USA.
A 56-year-old male presented to the clinic with complaints of multiple skin lesions. A complete blood count (CBC) was not available. No constitutional symptoms were present, and physical examination revealed tender skin lesions of the back, arms, legs, and scalp.
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January 2025
Inflammatory Immune-Mediated Chronic Skin Diseases Laboratory (GC26), Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba/Reina Sofia University Hospital, Menendez Pidal Ave, 14004, Córdoba, Spain.
Introduction: Non-segmental vitiligo (NSV) is an autoimmune condition characterized by melanocyte loss. While skin-specific mechanisms are well-studied, systemic immune dysregulation contributing to NSV pathogenesis remains unclear.
Objective: This study employs a multi-omic single-cell approach to investigate circulating immune cells in NSV, integrating transcriptional and chromatin accessibility data.
J Int AIDS Soc
February 2025
Children's National Hospital, Washington, DC, USA.
Introduction: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was efficacious and well tolerated in children/adolescents with HIV (aged ≥6 years, weighing ≥25 kg) in a Phase 2/3 study. Here, we report data from children aged ≥2 years and weighing ≥14-<25 kg.
Methods: This is an analysis of data from the youngest cohort in an open-label, multicentre, multi-cohort, single-group, international study of children/adolescents with HIV.
Adv Sci (Weinh)
January 2025
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China.
The immunosuppressive microenvironment in pancreatic cancer, characterized by low tumor-specific T cells and excessive fibrosis, limits the effectiveness of immunotherapy. Here, three datasets and multi-immunofluorescence staining of tissue microarrays in pancreatic cancer indicate that mesothelin (MSLN) expression negatively correlates with cytotoxic T cells in tumor. Anti-MSLN antibody (αMSLN) treatment of pancreatic cancer in vivo can significantly increase T cell infiltration.
View Article and Find Full Text PDFCell Biochem Funct
February 2025
Departamento de Ciências BioMoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
Increased oxidative stress and apoptosis are key mechanisms of thymic atrophy induced by cyclophosphamide (CYP). Atrophy leads to changes in the thymic microenvironment and disrupts T cell maturation. The hormone melatonin displays antioxidant and antiapoptotic effects.
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