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

SUBMITTER: Blanch-Lombarte O 

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

REPOSITORIES: biostudies-literature