Transmitted Drug Resistance Mutations in Antiretroviral-Naïve Injection Drug Users with Chronic HIV-1 Infection in Iran.

Arash Memarnejadian,Ehsan Mostafavi,Rouhollah Vahabpour,Seyed Ali Mansouri,Mohammad Abdi,Leila Sadeghi,Mohammad Reza Aghasadeghi,Shahoo Menbari,Luis Menéndez-Arias

doi:10.1371/journal.pone.0126955

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-naïve, chronically infected individuals who are, in fact, the main candidates for ART initiation. To address this issue, we collected blood samples from 40 ART-naïve 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.

Highlights

Incorporation of highly active antiretroviral therapy (HAART) into clinical practice has resulted in a 60% to 80% decline in rates of Acquired Immunodeficiency Syndrome (AIDS) death and hospitalization [1]
K103N associated with resistance to efavirenz (EFV) and nevirapine (NVP) was the only mutation to non-nucleoside reverse transcriptase inhibitors (NNRTIs; 5%)
We found no surveillance drug-resistant mutations (SDRMs) to protease inhibitors (PIs); based on the mutations listed in the International Antiviral Society-USA (IAS-USA) panel, 13minor mutations were detected in the PR region, of which M36I, H69K, and L89M/V/I were found in all 40 (100%) andK20R/ T was detected in 37 (92.5%) samples

Summary

Introduction

Incorporation of highly active antiretroviral therapy (HAART) into clinical practice has resulted in a 60% to 80% decline in rates of Acquired Immunodeficiency Syndrome (AIDS) death and hospitalization [1]. Current treatment guidelines recommend routine laboratory testing to assess drug resistance-associated mutations (DRAMs) in patients with acute and chronic infections prior to ART initiation to optimize the treatment regimen [11,12,13]. These are recommended in countries scaling up ART and in areas where primary resistance has been consistently documented[12, 14]. Lack of testing for baseline resistance, in addition to, other factors including interruption in treatment due to disruption in drug supply, or as a result of financial restrictions and improper administration of drug regimens are the major causes for the occurrence and expansion of drug resistance in developing countries [2]

Methods

Results

Conclusion