The relationship between clinical changes in stavudine activity and stavudine resistance was investigated in 16 human immunodeficiency virus (HIV)-infected children who received stavudine monotherapy for 18 months. Seven patients responded well to stavudine therapy, 3 experienced transient reductions in virus load, and all others had no detectable virologic response. In both the responders and nonresponders, no changes in stavudine susceptibility or specific baseline/emergent mutations in reverse transcriptase were observed. Only posttherapy HIV isolates from transient responders had elevated IC(50) values for stavudine. In 2 of the 3 transient responders, substitutions at codons 41, 210, and 215 were selected. The significance of these mutations was confirmed in viral competition experiments, site-directed mutagenesis, and in vitro selection. Selection of mutations previously associated with zidovudine resistance can be an important mechanism through which HIV may escape stavudine. The effect of these mutations on phenotypic stavudine susceptibility is relatively small but apparently large enough to be clinically significant.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1086/339817 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Thymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 Subtype C Reverse Transcriptase to Islatravir.
Viruses
December 2024
HIV Pathogenesis Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL.
View Article and Find Full Text PDFRepurposing zidovudine and 5-fluoro-2'-deoxyuridine as antibiotic drugs made possible by synergy with both trimethoprim and the mitochondrial toxicity-reducing agent uridine.
J Antimicrob Chemother
December 2024
Ultupharma AB, Södra Rudbecksgatan 13, Uppsala SE-752 36, Sweden.
Objectives: The increasing frequency of antibiotic-resistant bacterial infections is a major public health challenge, and new antibiotic drugs are urgently needed. A rapid solution to the problem is to repurpose clinically approved compounds with antibacterial properties, such as the nucleoside analogues zidovudine (azidothymidine) or 5-fluoro-2'-deoxyuridine. Here we report the in vitro and in vivo antibacterial properties of double and triple combinations of azidothymidine or 5-fluoro-2'-deoxyuridine with uridine and/or trimethoprim.
View Article and Find Full Text PDFOutcomes of HIV-infected children on antiretroviral therapy for at least 10 years at the Essos Hospital Centre, Cameroon: contributing to the elimination of paediatric AIDS in tropical settings.
J Trop Pediatr
December 2024
African Population and Health Research Centre, Dakar, Dakar 12500, Senegal.
Evidence on long-term outcomes of children receiving antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is of utmost importance to optimize current and future therapeutic strategies for HIV. We sought to ascertain the long-term responses among ART-experienced children and their potential implications. A retrospective, observational, facility-based cohort study was conducted among 136 ART-experienced children monitored for 10 years (2007-2017) at the Essos Hospital Centre in Yaoundé, Cameroon.
View Article and Find Full Text PDFInvestigating the role of nucleoside reverse transcriptase inhibitors in modulating lipotoxicity: Effects on lipid dynamics stress pathways, and insulin resistance on the function of dopaminergic neurons.
Biomed Pharmacother
December 2024
Department of Toxicology, Faculty of Pharmacy, Wroclaw Medical University, Wrocław, Poland.
Despite decades of advancements in HIV treatment, the persistence of viral reservoirs necessitates lifelong therapy, complicating efforts to fully control the infection. Nucleoside reverse transcriptase inhibitors (NRTIs) remain a cornerstone of HIV treatment, but long-term use is associated with side effects, including lipid metabolism disruption and neurocognitive disorders. There is a gap in understanding the safety of antiretrovirals and their impact on lipid toxicity in the central nervous system.
View Article and Find Full Text PDFCost-effectiveness of viral load testing for transitioning antiretroviral therapy-experienced children to dolutegravir in South Africa: a modelling analysis.
Lancet Glob Health
December 2024
Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, MA, USA; Harvard University Center for AIDS Research, Boston, MA, USA. Electronic address:
Background: For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value.
Methods: We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir-lamivudine-efavirenz: (1) continue current ART (no dolutegravir; abacavir-lamivudine-efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir-lamivudine-dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir-lamivudine-dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine-lamivudine-dolutegravir, 30%).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!