Background: Human immunodeficiency virus type 1 (HIV-1) drug resistance mutation testing has become a useful tool in assessing antiretroviral treatment and managing patient care. As these complex molecular genotyping procedures move into routine use in clinical laboratories, the need arises for quality control procedures that will ensure that drug resistance associated mutations are accurately identified.
Objectives: The AcroMetrix HIV-1 Resistance Proficiency Program was designed to assess proficiency in the identification of HIV-1 drug resistance mutations using molecular genotyping methods. This study describes results obtained from a variety of laboratories participating in the 2001 proficiency program.
Study Design: The 2001 program included three challenges, each comprised of five blind-labeled panel members containing mutations in the reverse transcriptase (RT) and/or protease (PR) genes. Challenge HIV-R01 was distributed to 19 laboratories in May 2001, challenge HIV-R02 was shipped to 25 participants in August 2001, and challenge HIV-R03 was distributed to 31 laboratories in November 2001.
Results And Conclusion: Participants correctly identified 74% of the total number of mutations and 82% of the panel members (i.e. all appropriate mutations detected in each panel member) in HIV-R01, 88% of the mutations and 91% of the panel members in HIV-R02, and 75% of the mutations and 52% of the panel members in HIV-R03. The AcroMetrix HIV-1 Resistance Proficiency Program, along with AcroMetrix's Internet-based reporting system (http://www.labqc.org), provides a useful tool for assessing operator proficiency within individual laboratories, and for comparing HIV-1 resistance testing proficiency among laboratories and technology platforms worldwide.
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http://dx.doi.org/10.1016/s1386-6532(02)00191-9 | DOI Listing |
J Mol Diagn
January 2025
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States. Electronic address:
Single nucleotide variations (SNVs) and polymorphisms (SNPs) are characteristic biomarkers in various biological contexts, including pathogen drug resistances and human diseases. Tools that lower the implementation barrier of molecular SNV detection methods would provide greater leverage of the expanding SNP/SNV database. The oligonucleotide ligation assay (OLA) is a highly specific means for detection of known SNVs and is especially powerful when coupled with polymerase chain reaction (PCR).
View Article and Find Full Text PDFJ Virol
January 2025
SA MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa.
The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity.
View Article and Find Full Text PDFNarra J
December 2024
Department of Clinical Pathology, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
Indonesia has one of the highest HIV infection rates in Southeast Asia. The use of dolutegravir, an integrase strand transfer inhibitor (INSTI), as a first-line treatment underscores the need for detailed data on INSTI drug resistance mutations (DRMs). Currently, there is a lack of comprehensive data on DRMs INSTI and other HIV drug resistance in Indonesian patients, both pre- and post-treatment.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China; Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, China; Institute of Flow Chemistry and Engineering, School of Chemistry and Materials, Jiangxi Normal University, Nanchang, 330022, China. Electronic address:
In order to enhance the anti-HIV-1 potency and selectivity of the previously reported compound 3 (EC = 27 nM, SI = 1361), a series of novel biphenyl-diarylpyrimidine derivatives were developed by employing structure-based drug design strategy. Among these derivatives, compound M44 demonstrated the most potent inhibitory activity against wild-type (WT) HIV-1 as well as five drug-resistant mutants (EC = 5-148 nM), which were 5-173 times more potent than that of 3 (EC = 27-9810 nM). Furthermore, this analogue exhibited approximately 11-fold lower cytotoxicity (CC = 54 μM) than that of etravirine and rilpivirine.
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2025
Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière hospital, AP-HP, Pierre Louis Institute of Epidemiology and Public Health (iPLESP), INSERM U1136, Paris, France.
Background: Doravirine is licensed in patients living with HIV (PWH) harbouring no prior resistance to any NNRTIs. We aimed to evaluate in real life the efficacy of doravirine with prior NNRTI virological failure and NNRTI resistance-associated mutations (RAMs).
Methods: This observational study included PWH switched to a doravirine-containing regimen between 30 September 2019 and 1 May 2022, with an HIV-1 RNA of ≤50 copies/mL and past NNRTI-RAMs.
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