Genetic Changes in HIV-1 Gag-Protease Associated with Protease Inhibitor-Based Therapy Failure in Pediatric Patients. AIDS Res Hum Retroviruses, 31(8): 776-82 (2015).

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Title: Genetic Changes in HIV-1 Gag-Protease Associated with Protease Inhibitor-Based Therapy Failure in Pediatric Patients
Authors: Giandhari J, Basson AE, Coovadia A, Kuhn L, Abrams AJ, Strehlau R, Morris L, Hunt GM.
Journal: AIDS Res Hum Retroviruses,31(8):776-82 (2015)

Journal Impact Factor (I.F.): 2.457
Number of citations (Google Scholar): 3

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 Cinfected 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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Citation: Giandhari J, Basson AE, Coovadia A, Kuhn L, Abrams AJ, Strehlau R, Morris L, Hunt GM. Genetic Changes in HIV-1 Gag-Protease Associated with Protease Inhibitor-Based Therapy Failure in Pediatric Patients AIDS Res Hum Retroviruses,31(8):776-82 (2015).


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