Abstract: RESULTS: Of 15 infants, tested at a median age of 3.4 months after birth, 2 (13%) had non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs (K103N and Y181C) by bulk sequencing, whereas PGM detected 4 (26%) and MiSeq 5 (30%).
Introduction: A recent study found good correlation of Roche 454 sequencing for K103N and Y181C, when screening PMTCT exposed children (less than 2 years of age) prior to cART initiation.
Result: For the infant with K103N, detected by bulk sequencing, both Ion PGM and MiSeq additionally detected V106A/M and Y181C DRMs.
Discussion: The additional detection of Y181C in the infa
Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches.
PMID: 25626145
2015
European journal of medicinal chemistry
Abstract: Additionally, 7d demonstrated weak activity against the double mutant HIV-1 strain (K103N + Y181C), and was more efficient than NVP in a RT inhibition assay.
Prevention of mother-to-child HIV-1 transmission in Burkina Faso: evaluation of vertical transmission by PCR, molecular characterization of subtypes and determination of antiretroviral drugs resistance.
Structure-based evaluation of non-nucleoside inhibitors with improved potency and solubility that target HIV reverse transcriptase variants.
PMID: 25700160
2015
Journal of medicinal chemistry
Method: Final clones for the RT (Y181C) and RT (K103N/Y181C) were verified by DNA sequencing.
Method: For the RT (K103N/Y181C):1 complexes, crystals were first obtained using cocrystallization then dehydrated using similar methods described previously.
Method: For the RT (Y181C):1, RT (Y181C):2, and RT (K103N/Y181C):2 complexes, crystal soaking techniques were used to obtain the C2 crystal forms.
Method: Initially, the
Predicted residual activity of rilpivirine in HIV-1 infected patients failing therapy including NNRTIs efavirenz or nevirapine.
PMID: 25704446
2015
Clinical microbiology and infection
Abstract: Most prevalent RPV-RAMs after nevirapine experience were Y181C and H221Y, whereas L100I+K103N, Y188L and K101E occurred most in efavirenz-experienced patients.
Characterization of HIV drug resistance mutations among patients failing first-line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia.
Abstract: Analysis of reverse transcriptase revealed M184V (88%), K103N/S (32%), and Y181C/I/V (41%) DRMs, with the latter conferring reduced susceptibility to the salvage therapy candidates etravirine and rilpivirine.
Result: Of note, there was a high prevalence of Y181C/I/V (n = 28, 41% cumulatively) that confers reduced susceptibility to both rilpivirine (RPV) and etravirine (ETR), and Y188L (n = 5, 7%) which leads to reduced susceptibility to RPV.
Result: The most prevalent NNRTI mutations were Y181C/I/V (n = 24, 35%), (n = 3, 4%), and (n = 1 (1%), respectively, K103N/S (n = 21 (32%) and n = 1 [1%]), PMID: 25788547
2015
Journal of clinical microbiology
Abstract: ARMS-PCR's limits of detection for mutations M184V, T215Y/F, K103N, and Y181C were <75 copies/ml, 143 copies/ml, 143 copies/ml, and 836 copies/ml, respectively.
Abstract: The ARMS-PCR assay was able to detect M184V, T215Y/F, K103N, and Y181C mutations with sensitivities of 96.8%, 85.7%, 91.3%, and 70%, respectively, and specificities of 90.6%, 95%, 100%, 96.9%, respectively, compared with data on sequencing.