Transmitted drug resistance mutations in antiretroviral-naïve injection drug users with chronic HIV-1 infection in Iran

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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.

Figures

  • Table 1. Demographics and laboratory data of study samples.
  • Fig 1. Summarized phylogenetic tree of 40 Sanandaj (SDJ) samples based on protease and reversetranscriptase (PR-RT, 1017 bp) sequences. Tree was constructed using neighbor-joining method with 1000 replicates. As a summarized representation, only reference sequences from HIV-1 subtypes/CRFs previously reported in Iran including B (●; closed circles), D (□; open squares), A1 (&; closed squares), A2 ( ; open circles), CRF01_AE (◆;; closed diamonds) and CRF35_AD (▲;; closed triangle) are included. GenBank accession numbers for the reference sequences, as well as, bootstrap values over 70% are shown. The scale bar represents nucleotidesubstitutions per site.
  • Table 2. Frequency of HIV-1 drug resistance-associated mutations among 40 sequenced samples.

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Memarnejadian, A., Menbari, S., Mansouri, S. A., Sadeghi, L., Vahabpour, R., Aghasadeghi, M. R., … Abdi, M. (2015). Transmitted drug resistance mutations in antiretroviral-naïve injection drug users with chronic HIV-1 infection in Iran. PLoS ONE, 10(5). https://doi.org/10.1371/journal.pone.0126955

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