Background: Active tuberculosis is common among human immunodeficiency virus (HIV)-infected persons living in tuberculosis-endemic areas, but the hazard of subsequent tuberculosis disease has not been quantified in a single prospective cohort.
Methods: Among HIV-infected, BCG-immunized adults with CD4 counts ≥200 cells/μL who received placebo in the DarDar tuberculosis vaccine trial in Tanzania, we compared the prospective risk of active tuberculosis between subjects who did and who did not report prior active tuberculosis. All subjects with a positive tuberculin skin test without prior active tuberculosis were offered isoniazid preventive treatment. Definite or probable tuberculosis was diagnosed during active follow-up using rigorous published criteria.
Results: We diagnosed 52 cases of definite and 92 cases of definite/probable tuberculosis among 979 subjects during a median follow-up of 3.2 years. Among the 80 subjects who reported prior active tuberculosis, 11 (13.8%) subsequently developed definite tuberculosis and 17 (21.3%) developed definite/probable tuberculosis, compared with 41 (4.6%) and 75 (8.3%), respectively, of 899 subjects without prior active tuberculosis (definite tuberculosis risk ratio [RR], 3.01; 95% confidence interval [CI], 1.61-5.63, P < .001; definite/probable tuberculosis RR, 2.55; 95% CI, 1.59-4.09, P < .001). In a Cox regression model adjusting for age, CD4 count, and isoniazid receipt, subjects with prior active tuberculosis had substantially greater hazard of subsequent definite tuberculosis (hazard radio [HR], 3.69; 95% CI, 1.79-7.63, P < .001) and definite/probable tuberculosis (HR, 2.78; 95% CI, 1.58-4.87, P < .001).
Conclusions: Compared to subjects without prior tuberculosis, the hazard of active tuberculosis is increased 3-fold among HIV-infected adults with prior active tuberculosis. Clinical Trials Registration. NCT0052195.
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http://dx.doi.org/10.1093/cid/cis798 | DOI Listing |
Antimicrob Agents Chemother
December 2024
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Ethambutol is used to treat tuberculosis (TB) in individuals living with HIV. Low concentrations of ethambutol have been reported in patients dosed with the World Health Organization (WHO)-recommended first-line regimen. We analyzed the pharmacokinetics of ethambutol in 61 HIV-positive individuals diagnosed with drug-sensitive TB enrolled in the tuberculosis and highly active antiretroviral therapy (TB-HAART) study.
View Article and Find Full Text PDFJ Biomol Struct Dyn
December 2024
Amity Institute of Biotechnology, Amity University, Kolkata, India.
The first FDA approved, MDR-TB inhibitory drug bedaquiline (BDQ), entraps the c-ring of the proton-translocating F region of enzyme ATP synthase of , thus obstructing successive ATP production. Present-day BDQ-resistance has been associated with cardiotoxicity and mutation(s) in the atpE gene encoding the c subunit of ATP synthase (ATPc) generating five distinct ATPc mutants: Ala63→Pro, Ile66→Met, Asp28→Gly, Asp28→Val and Glu61→Asp. We created three discrete libraries, first by repurposing bedaquiline via scaffold hopping approach, second one having natural plant compounds and the third being experimentally derived analogues of BDQ to identify one drug candidate that can inhibit ATPc activity more efficiently with less toxic properties.
View Article and Find Full Text PDFAirway multiciliated cells (MCs) maintain respiratory health by clearing mucus and trapped particles through the beating of motile cilia. While it is known that ciliary lengths decrease along the proximal-distal (P-D) axis of the tracheobronchial tree, how this is regulated is unclear. Here, we demonstrate that canonical Notch signaling in MCs plays a critical role in stabilizing ciliary length.
View Article and Find Full Text PDFCureus
November 2024
Emergency Medicine & Neurology, University of Central Florida, Orlando, USA.
Dr. Soumya Swaminathan, a renowned Indian physician and scientist, revolutionized medical practices through her significant contributions to tuberculosis and human immunodeficiency virus research, yielding a lasting impact on global health. As the former Chief Scientist of the World Health Organization, her committed approach to healthcare has been instrumental in linking scientific research and evidence to policy development.
View Article and Find Full Text PDFCureus
November 2024
Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, MAR.
Hepatic sarcoidosis is rare, and its similarity to liver metastases complicates the diagnosis. This mimicry requires a thorough diagnostic investigations to exclude neoplasia and other granulomatous diseases, particularly tuberculosis. A 36-year-old male presented with a two-month history of right hypochondrial tenderness, anorexia, asthenia, and weight loss.
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