Drug Resistance-Associated Genotypic Alterations in ART-Naives in North India

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Drug Resistance-Associated Genotypic Alterations in the pol Gene of

HIV Type 1 Isolates in ART-Naive Individuals in North India

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To cite this paper:

Sunil K. Arora, Sachin Gupta, Jaideep S. Toor, Anuj Singla. AIDS

Research and Human Retroviruses. February 1, 2008, 24(2): 125-130.

doi:10.1089/aid.2007.0156.

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Department of Immunopathology, Postgraduate Institute of Medical

Education and Research, Chandigarh, India.

ABSTRACT

We genotyped the RT and PI regions of the pol gene of HIV-1 from

treatment-naive infected individuals in North India and evaluated

their possible physiological relevance and association with drug

resistance.

Plasma samples from 52 newly diagnosed HIV-1-infected drug-naive

individuals were subjected to CD4+ cell count and plasma viral load.

For genotyping, the protease and RT regions of the pol gene were

amplified from cDNA reverse transcribed from plasma viral RNA by

single or nested polymerase chain reaction (PCR). Sequences of

amplified products were analyzed for mutations using the Stanford DR

and REGA database.

Two out of 49 amplicons showed mutations at known " major " subtype B

drug resistance positions (one each in protease and RT). In the

protease region it showed a major drug resistance mutation at M46I as

well as " minor " positions F53L and T74P. In the RT gene, one patient

showed a mutation at major NNRTI position G190V. Forty-nine percent

had mutations in the hinge (M36I, R41K, H69K) and á-helix (L89M)

regions of the C-virus protease, which has been linked to increased

catalytic activity. Our study indicates that a number of major

mutations associated with resistance to PIs, NNRTIs, and NRTIs do

exist, though at a low frequency, among HIV-1 isolates from treatment-

naive individuals in North India.

Many minor or accessory mutations related to resistance to PIs and

NRTIs are also present as the variants. These results point to the

greater biochemical fitness of subtype C protease and faster decrease

in drug sensitivity.