An estimated 1.5 million Kenyans are HIV-seropositive, with 1.1 million on antiretroviral therapy (ART), with the majority of them unaware of their drug resistance status. In this study, we assessed the prevalence of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors, and the variables associated with drug resistance in patients failing treatment in Nairobi, Kenya.This cross-sectional study utilized 128 HIV-positive plasma samples obtained from patients enrolled for routine viral monitoring in Nairobi clinics between 2015 and 2017. The primary outcome was human immunodeficiency virus type 1 (HIV-1) drug resistance mutation counts determined by Sanger sequencing of the polymerase (pol) gene followed by interpretation using Stanford's HIV Drug Resistance Database. Poisson regression was used to determine the effects of sex, viral load, age, HIV-subtype, treatment duration, and ART-regimen on the primary outcome.HIV-1 drug resistance mutations were found in 82.3% of the subjects, with 15.3% of subjects having triple-class ART resistance and 45.2% having dual-class resistance. NRTI primary mutations M184 V/I and K65R/E/N were found in 28.8% and 8.9% of subjects respectively, while NNRTI primary mutations K103N/S, G190A, and Y181C were found in 21.0%, 14.6%, and 10.9% of subjects. We found statistically significant evidence (P = .013) that the association between treatment duration and drug resistance mutations differed by sex. An increase of one natural-log transformed viral load unit was associated with 11% increase in drug resistance mutation counts (incidence rate ratio [IRR] 1.11; 95% CI 1.06-1.16; P < .001) after adjusting for age, HIV-1 subtype, and the sex-treatment duration interaction. Subjects who had been on treatment for 31 to 60 months had 63% higher resistance mutation counts (IRR 1.63; 95% CI 1.12-2.43; P = .013) compared to the reference group (<30 months). Similarly, patients on ART for 61 to 90 months were associated with 133% higher mutation counts than the reference group (IRR 2.33; 95% CI 1.59-3.49; P < .001). HIV-1 subtype, age, or ART-regimen were not associated with resistance mutation counts.Drug resistance mutations were found in alarmingly high numbers, and they were associated with viral load and treatment time. This finding emphasizes the importance of targeted resistance monitoring as a tool for addressing the problem.
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http://dx.doi.org/10.1097/MD.0000000000027460 | DOI Listing |
Microbiol Res
January 2025
State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:
Pseudomonas aeruginosa is a prominent respiratory pathogen in cystic fibrosis (CF) patients, thriving in the hypoxic airway mucus. Previous studies have established the role of the oxygen-binding hemerythrin, Mhr, in enhancing P. aeruginosa's fitness under microaerobic conditions.
View Article and Find Full Text PDFHepatol Commun
February 2025
Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Background: Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.
Methods: Rats with MASLD were randomly assigned to undergo DJB or sham surgery.
ACS Appl Mater Interfaces
January 2025
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Multidrug resistance (MDR) facilitates tumor recurrence and metastasis, which has become a main cause of chemotherapy failure in clinical. However, the current therapeutic effects against MDR remain unsatisfactory, mainly hampered by the rigid structure of drug-resistant cell membranes and the uncontrolled drug release. In this study, based on a sequential drug release strategy, we engineered a core-shell nanoparticle (DOX-M@CaP@ATV@HA) depleting cholesterol for reverse tumor MDR.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Biological Sciences, Purdue University Fort Wayne, Fort Wayne, Indiana, United States of America.
Present study aimed at improving the immune and antioxidant response of Pacific white shrimp (Litopenaeus vannamei) cultured at high stocking density fed with 0.2% supplementation of lauric acid (LA) and N-acetyl-L-cysteine (NAC). Shrimp (initial average weight = 0.
View Article and Find Full Text PDFProtein Cell
January 2025
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China.
Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering.
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