Background: 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) contains an ethynyl moiety and the 3'-hydroxyl and exerts highly potent activity against various HIV type-1 (HIV-1) strains including multi-drug-resistant variants.
Methods: Comparative selection passages against EFdA, lamivudine (3TC), tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) or BMS-986001 (Ed4T) were conducted using a mixture of 11 highly multi-drug-resistant clinical HIV-1 isolates (HIV11MIX) as a starting virus population.
Results: Before selection, HIV11MIX was sensitive to EFdA with a 50% inhibitory concentration (IC50) of 0.032 μM, less susceptible to TDF and Ed4T with IC50s of 0.57 and 2.6 μM, respectively, and highly resistant to 3TC and FTC with IC50s>10 μM. IC50s of TDF against HIV11MIX exposed to EFdA and TDF for 17 (HIV11MIX(EFdA-P17)) and 14 (HIV11MIX(TDF-P14)) passages were 8 and >10 μM, respectively, while EFdA remained active against HIV11MIX(EFdA-P17) and HIV11MIX(TDF-P14) with IC50s of 0.15 and 0.1 μM, respectively. Both selected variants were highly resistant against zidovudine, 3TC, Ed4T and FTC (IC50 values >10 μM).
Conclusions: The present data demonstrate that HIV11MIX developed resistance more rapidly against 3TC, FTC, TDF and Ed4T than against EFdA and that EFdA remained substantially active against TDF- and EFdA-selected variants. Thus, EFdA has a favourable resistance profile and represents a potentially promising new-generation nucleoside reverse transcriptase inhibitor.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3851/IMP2697 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Post-marketing quality evaluation of oxytocin injection and assessment of associated factors among selected health facilities in Addis Ababa, Ethiopia.
Sci Rep
October 2024
Department of Pharmacy, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.
Oxytocin is the principal drug and the primary choice for labor induction and postpartum hemorrhage prevention and treatment. The problems associated with oxytocin are not usually from its effectiveness, but they are from its compromised quality which may occur at the point of manufacturing, transportation, and storage. The main objective of this study was to assess the status of oxytocin injection quality and associated factors in the health facilities located in Addis Ababa city, Ethiopia.
View Article and Find Full Text PDFQuality assessment of common anti-malarial medicines marketed in Gambella, National Regional State, South Western-Ethiopia.
Malar J
September 2024
Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, P.O Box.1176, Addis Ababa, Ethiopia.
Background: Over the past years, there has been a growing concern that a considerable amount of anti-malarial supply in the underdeveloped world particularly in the private sector, is of poor quality. The World Health Organization (WHO) has received about 1500 reports that mentions instances of substandard and falsified products since 2013. The majority of the reports concerned antibiotics and anti-malarials.
View Article and Find Full Text PDFPost-marketing quality surveillance of selected antibacterial agents marketed in porous borders; the case of Ethiopia-Sudan-Eritrea border.
PLoS One
August 2024
Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Background: The presence of poor-quality medicines is becoming a public health threat in many parts of the world, particularly in developing countries. Antibiotics are among the most common anti-infective medicines that are highly prone to this problem.
Objectives: The purpose of this study was to assess the quality of selected antibacterials that are marketed in Setit Humera and West Gondar Zones, North West Ethiopia, which are located on the Ethiopian side of the Ethiopia-Sudan-Eritrea border.
Applicability of selected Brighton Collaboration case definitions in low-resource settings: A prospective hospital-based active surveillance in Addis Ababa, Ethiopia.
Vaccine
October 2024
Brighton Collaboration, Task Force for Global Health, Decatur, GA, USA; Global Health Program, College of Public Health, National Taiwan University, Taipei, Taiwan; National Taiwan University Children's Hospital, Taipei, Taiwan.
Introduction: Standardizing case definitions for priority vaccine safety conditions facilitates uniform evaluation and consolidation of data obtained from different settings. The Brighton Collaboration case definitions (BCCD) were created to support this harmonization and enable classification from level 1 (most certain) to level 5 (not a case) of certainty. Assessing the performance of BCCD in practice is critical, particularly in resource-limited settings, where many new vaccines may be introduced without prior monitoring in high-income countries.
View Article and Find Full Text PDFAssessment of the extent and monetary loss in the selected public hospitals in Jimma Zone, Ethiopia: expired medicine perspectives.
Front Med (Lausanne)
February 2024
Jimma University Laboratory of Drug Quality (JuLaDQ) and School of Pharmacy, Institute of Health, Jimma University, Jimma, Oromia, Ethiopia.
Introduction: Medicine plays a crucial role in the field of healthcare as a therapeutically significant pharmaceutical product. By effectively preventing diseases, medicine has the power to save countless lives and improve the quality of life for people worldwide. However, despite hospitals' efforts to provide medical care to patients, a significant issue arises from the substantial amount of drugs that go unused due to expiration dates.
View Article and Find Full Text PDFWant 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!