Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users With Chronic Hiv-1 Infection in Iran Publisher Pubmed



Memarnejadian A^{1, 7} ; Menbari S² ; Mansouri SA³ ; Sadeghi L⁴ ; Vahabpour R⁵ ; Aghasadeghi MR¹ ; Mostafavi E⁶ ; Abdi M² Show Affiliations
Source: PLoS ONE Published:2015

Abstract

The growing incidence and transmission of drug resistant HIV-1 strains due to widespread use of antiretroviral therapy (ART) can jeopardize the success of first-line ART. While there is a known moderate prevalence of transmitted drug resistance (TDR) among newly infected Iranians, no data exist about the rate of these primary resistance mutations among the ART-naive, chronically infected individuals who are, in fact, the main candidates for ART initiation. To address this issue, we collected blood samples from 40 ART-naive injection drug-users (IDUs) with chronic HIV-1 infection (seroconversion time ranging from 2 to 9 years) living in Sanandaj, Iran, followed by sequencing of the protease and reverse-transcriptase regions from their HIV-1 genome. Phylogenetic analyses of the sequenced regions revealed that all samples were CRF35-AD. Transmitted resistance mutations were interpreted as surveillance drug-resistant mutations (SDRMs) based on the world health organization (WHO) algorithm. The frequency of SDRMs to any class of antiretroviral drugs was 15%, which included mutations to nucleoside reverse transcriptase inhibitors (NRTIs, 10%), with M41L and M184V as the most common (5%), and non-nucleoside reverse transcriptase inhibitors (NNRTIs, 5%), with K103N as the only detected mutation (5%). Although not in the WHO SDRMs list, several minor protease inhibitor resistant mutations listed in the International Antiviral Society-USA panel were identified, of which M36I, H69K, L89M/V/I (each one 100%) and K20R/T (92.5%) can be considered as polymorphic signatures for CRF35-AD.The relatively high rate of TDR mutations in our study raises concerns about the risk of treatment failure in chronically infected IDUs of Sanandaj city. These results suggest that routine resistance testing should be considered before the therapy initiation in this area. Additional surveillance studies are required to generalize this deduction to other cities of Iran. © 2015 Memarnejadian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.