Drug resistance mutations in protease gene of HIV-1 subtype C infected patient population

Abstract

Failure of antiretroviral therapy (ART) in HIV-1 infection is a critical issue for the physicians treating HIV patients. The major cause of drug failure is the development of resistance mutations in reverse transcriptase (RT) and/or protease (PR) genes. Mutations associated with drug resistance decrease drug effectiveness. This study was conducted to assess drug resistance profile of the entire PR gene in 90 HIV-1 patients consisting of 23 ART non-responsive, 32 ART responsive and 35 drug naive patients. It was observed that the majority of the sequences (94.4%) belonged to subtype C and (5.5%) to subtype A1. The ART non-responsive and responsive patients were treated with either first line of ART regimen (two NRTI and one NNRTI) or second line of ART regimen that included additional one protease inhibitor (PI). All the patients in each group except one responsive patient had various minor resistance mutations. Thus, drug failures in ART non-responsive patients may not always be due to drug resistance mutations instead other factors may also be responsible for drug failures such as non-compliance, suboptimal dose or drug interaction. The presence of minor drug resistance mutations in drug naive patients is suggestive of transmitted resistance mutations.

Keywords: ART; Drug naive patients; Drug resistance; HIV-1; Protease gene; Protease inhibitors.

Fig. 1

Phylogenetic relationship based on protease gene sequences (non-responsive group) of HIV-1 with other reported subtypes and consensus sequences from other clades. Consensus sequences and other sequences included in the tree are obtained from Los Alamos HIV Sequence Database. The clusters are indicated in the callouts. The bootstrapping was done with SEQBOOT (replications set as 1000). The scale bar indicates nucleotide substitution. Our study populations have been indicated as INHNRP3

Fig. 2

Phylogenetic relationship based on protease gene sequences (responsive group) of HIV-1 with other reported subtypes and consensus sequences from other clades. Consensus sequences and other sequences included in the tree are obtained from Los Alamos HIV Sequence Database. The clusters are indicated in the callouts. The bootstrapping was done with SEQBOOT (replications set as 1000). The scale bar indicates nucleotide substitution. Our study populations have been indicated as INHRP02

Fig. 3

Phylogenetic relationship based on protease gene sequences (drug naive group) of HIV-1 with other reported subtypes and consensus sequences from other clades. Consensus sequences and other sequences included in the tree are obtained from Los Alamos HIV Sequence Database. The clusters are indicated in the callouts. The bootstrapping was done with SEQBOOT (replications set as 1000). The scale bar indicates nucleotide substitution. Our study populations have been indicated as INJMIHNP