Journal of Antivirals & Antiretrovirals
Open Access

Abstract

Polymorphisms in HIV-1 Subtype C Reverse Transcriptase and Protease Genes in a Patient Cohort from Mumbai

Ritwik Dahake, Shraddha Mehta, Sneha Yadav, Abhay Chowdhary and Ranjana A Deshmukh

Objectives: Developed countries have been alarmed at the rates of primary/transmitted drug resistance of HIV-1. There is a debate on the validity of certain polymorphisms in HIV-1 Subtype C mutations related to consensus Subtype B sequences being associated with and sometimes mistaken as, primary resistance. In this preliminary study, we have determined polymorphisms in reverse transcriptase (RT) and protease (PR) genes of HIV-1 Subtype C from a patient cohort in Mumbai, India.

Methods: The study was performed with plasma samples from twenty-four patients (antiretroviral therapy experienced as well as drug-naive) employing a ‘home-brew’ semi-nested reverse-transcriptase-PCR followed by sequencing and sequence analysis. The Stanford HIV drug-resistance database was used for analysis and interpretation of polymorphisms and other drug-resistance mutations. We also analysed Surveillance Drug Resistance Mutations (SDRMs) for PR gene.

Results: Polymorphisms were determined at a mutational frequency of 0.1337 ± 0.042 in PR gene and 0.067 ± 0.014 in RT gene, while 16.6% and 12.5% samples harboured drug-resistance mutations in PR and RT genes respectively. Substitutions greater than 50% were at positions at L19, V82, M36, R41, L63, H69, L89 and I93 for PR gene and D121, K122, T165, K166, K173, D177, T200, Q207 and R211 for RT gene. Additionally, PR gene SDRMs were observed in 15.0% samples.

Conclusions: Our findings concur with previous findings that polymorphisms in HIV-1 Subtype C from India exist and re-iterate that these polymorphisms may also include a number of major and minor/accessory mutations associated with resistance. Most of the drug-resistance databases available online are based on Subtype B; hence, we recommend that HIV Subtype-specific drug-resistance databases be created to empower routine and unambiguous surveillance of drug-resistance prior to initiating antiretroviral therapy, especially while including Protease Inhibitors.