Genetic Changes in HIV-1 Gag-Protease Associated with Protease Inhibitor-Based Therapy Failure in Pediatric Patients

Overview

Journal AIDS Res Hum Retroviruses

Publisher Mary Ann Liebert

Specialty Infectious Diseases

Date 2015 Apr 29

PMID 25919760

Citations 9

Authors

Jennifer Giandhari

Adriaan E Basson

Ashraf Coovadia

Louise Kuhn

Elaine J Abrams

Renate Strehlau

Lynn Morris

Gillian M Hunt

Affiliations

Soon will be listed here.

Abstract

Studies have shown a low frequency of HIV-1 protease drug resistance mutations in patients failing protease inhibitor (PI)-based therapy. Recent studies have identified mutations in Gag as an alternate pathway for PI drug resistance in subtype B viruses. We therefore genotyped the Gag and protease genes from 20 HIV-1 subtype C-infected pediatric patients failing a PI-based regimen. Major protease resistance mutations (M46I, I54V, and V82A) were identified in eight (40%) patients, as well as Gag cleavage site (CS) mutations (at codons 373, 374, 378, 428, 431, 449, 451, and 453) in nine (45%) patients. Four of these Gag CS mutations occurred in the absence of major protease mutations at PI failure. In addition, amino acid changes were noted at Gag non-CS with some predicted to be under HLA/KIR immune-mediated pressure and/or drug selection pressure. Changes in Gag during PI failure therefore warrant further investigation of the Gag gene and its role in PI failure in HIV-1 subtype C infection.

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