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HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy.

ABSTRACT: BACKGROUND:Virological failure (VF) to boosted PIs with a high genetic barrier is not usually linked to the development of resistance-associated mutations in the protease gene. METHODS:From a cohort of 520 HIV-infected subjects treated with lopinavir/ritonavir or darunavir/ritonavir monotherapy, we retrospectively identified nine patients with VF. We sequenced the HIV-1 Gag-protease region and generated clonal virus from plasma samples. We characterized phenotypically clonal variants in terms of replicative capacity and susceptibility to PIs. Also, we used VESPA to identify signature mutations and 3D molecular modelling information to detect conformational changes in the Gag region. RESULTS:All subjects analysed harboured Gag-associated polymorphisms in the absence of resistance mutations in the protease gene. Most Gag changes occurred outside Gag cleavage sites. VESPA analyses identified K95R and R286K (P?

SUBMITTER: Blanch-Lombarte O

PROVIDER: S-EPMC7443716 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy.

Blanch-Lombarte Oscar O Santos José R JR Peña Ruth R Jiménez-Moyano Esther E Clotet Bonaventura B Paredes Roger R Prado Julia G JG

The Journal of antimicrobial chemotherapy 20200901 9

<h4>Background</h4>Virological failure (VF) to boosted PIs with a high genetic barrier is not usually linked to the development of resistance-associated mutations in the protease gene.<h4>Methods</h4>From a cohort of 520 HIV-infected subjects treated with lopinavir/ritonavir or darunavir/ritonavir monotherapy, we retrospectively identified nine patients with VF. We sequenced the HIV-1 Gag-protease region and generated clonal virus from plasma samples. We characterized phenotypically clonal varia ...[more]

PMID: 32556165

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Project description:Rationale and objectiveThe Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) published a set of minimum technical standards (MTS) to improve image quality and reduce variability in multiparametric prostate MRI. The effect of PIRADSv2 MTS on image quality has not been validated. We aimed to determine whether adherence to PI-RADSv2 MTS improves study adequacy and perceived quality.Materials and methodsSixty-two prostate MRI examinations including T2 weighted (T2W) and diffusion weighted image (DWI) consecutively referred to our center from 62 different institutions within a 12-month period (September 2017 to September 2018) were included. Six readers assessed images as adequate or inadequate for use in PCa detection and a numerical image quality ranking was given using a 1-5 scale. The PI-RADSv2 MTS were synthesized into sets of seven and 10 rules for T2W and DWI, respectively. Image adherence was assessed using Digital Imaging and Communications in Medicine (DICOM) metadata. Statistical analysis of survey results and image adherence was performed based on reader quality scoring (Kendall Rank tau-b) and reader adequate scoring (Wilcoxon test for association) for T2 and DWI quality assessment.ResultsOut of 62 images, 52 (83%) T2W and 38 (61%) DWIs were rated to be adequate by a majority of readers. Reader adequacy scores showed no significant association with adherence to PI-RADSv2. There was a weak (tau-b = 0.22) but significant (p value = 0.01) correlation between adherence to PIRADSv2 MTS and image quality for T2W. Studies following all PI-RADSv2 T2W rules achieved a higher median average quality score (3.58 for 7/7 vs. 3.0 for <7/7, p = 0.012). No statistical relationship with PI-RADSv2 MTS adherence and DWI quality was found.ConclusionAmong 62 sites performing prostate MRI, few were considered of high quality, but the majority were considered adequate. DWI showed considerably lower rates of adequate studies in the sample. Adherence to PI-RADSv2 MTS did not increase the likelihood of having a qualitatively adequate T2W or DWI.

Dataset Information

HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy.

Publications

HIV-1 Gag mutations alone are sufficient to reduce darunavir susceptibility during virological failure to boosted PI therapy.

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