Investigation of Drug-resistance substitutions in HIV-1 RT Protein in Iranian HIV Infected Patients
- Authors: Dehghani B.n.1, Hashempour T.N.1, Mousavi Z.n.1, Moayedi J.n.1, Hasanshahi Z.n.1, Rezaei E.n.1, Ghassabi F.n.1
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Affiliations:
- Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
- Section: SHORT COMMUNICATIONS
- URL: https://iimmun.ru/iimm/article/view/1383
- DOI: https://doi.org/10.15789/2220-7619-IOD-1383
- ID: 1383
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Full Text
Abstract
Background:
Currently, more than 37 million people are living with human immunodeficiency virus type 1. Reverse transcription (RT) is a main part in the life cycle of retroviruses which is responsible for synthesis of DNA complementary to an RNA or DNA template. Recently several inhibitors have been introduced to target RT protein; however, drug resistance is one of the greatest challenges in the improvement of effective treatment for human immunodeficiency virus (HIV) infection. Here, we determined the resistance mutations in the RT gene in treatment failure patients and searched for the dominant subtype among them.
Methods:
HIV viral load and a reverse transcriptase nested polymerase chain (RT-nested PCR) reactions were performed in 15 patients with treatment failure to amplify the RT gene. Drug resistance mutations, as well as the viral subtypes, were analyzed using by using several bioinformatics software and online tools.
Results:
The frequency of RT related drug-resistance mutations in patients was 33.3%, among which the major mutation consisted of 20% of all those occurring in codon 184. Moreover, the results showed 6.6% and 26.6% of patients were resistant to Non-Nucleoside RT Inhibitor (NNRTIs) and Nucleoside RT Inhibitors (NRTIs), respectively. In addition, the vast majority of samples (12 patients of 15) belonged to subtype CRF35-AD.
Conclusions:
The present study reports updates on the mutations related to RT resistance in Iranian HIV patients receiving treatment, show that 20% of the samples had a high-level of resistance to Lamivudine, and Emtricitabine which should be confirmed for further antiretroviral (AVR) regimens for HIV infected patients. Also, two new mutations related to resistance to Nevirapine, Doravirine, Zidovudine, and Stavudine were introduced in this investigation.
The present results could be used as predictive information on the response to anti-RT, and also highlight the importance of considering the periodic monitoring of HIV resistance test in HIV infected patients.
Keywords
About the authors
Behzad non Dehghani
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Email: dehghanibehzad@gmail.com
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Iran, Islamic Republic ofTayebeh Non Hashempour
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Email: thashem@iran.ir
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Iran, Islamic Republic ofZahra non Mousavi
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Email: Behzad1@iran.ir
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Iran, Islamic Republic ofJavad non Moayedi
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Email: jmoayaedi@gmail.com
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Zahra non Hasanshahi
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Email: 75hasanshai@gmail.com
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Esmaeil non Rezaei
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Email: behzad2@iran.ir
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Farzaneh non Ghassabi
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
Author for correspondence.
Email: fghasabi@iran.ir
Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
References
- Gilbert, M.T.P., et al., The emergence of HIV/AIDS in the Americas and beyond. Proceedings of the National Academy of Sciences, 2007. 104(47): p. 18566-18570.
- Dehghani, A., P. Dehghani, and B. Dehghani, HIV/AIDS knowledge and attitude among high school students in Shiraz, Iran in 2015. Journal of Midwifery and Reproductive Health, 2017. 5(2): p. 897-903.
- Blood, G.A.C., Human Immunodeficiency Virus (HIV). Transfusion Medicine and Hemotherapy, 2016. 43(3): p. 203.
- Das, K. and E. Arnold, HIV-1 reverse transcriptase and antiviral drug resistance. Part 1. Current opinion in virology, 2013. 3(2): p. 111-118.
- Cartwright, E.K., et al., Initiation of antiretroviral therapy restores CD4+ T memory stem cell homeostasis in simian immunodeficiency virus-infected macaques. Journal of virology, 2016. 90(15): p. 6699-6708.
- Santoro, M.M. and C.F. Perno, HIV-1 genetic variability and clinical implications. ISRN microbiology, 2013. 2013.
- Dehghani, B., et al., Functional and structural characterization of Ebola virus glycoprotein (1976–2015)—An in silico study. International Journal of Biomathematics, 2017. 10(08): p. 1750108.
- Dehghani, B., T. Hashempour, and Z. Hasanshahi, Using immunoinformatics and structural approaches to design a novel HHV8 vaccine. International Journal of Peptide Research and Therapeutics, 2019: p. 1-11.
- Dehghani, B., et al., Bioinformatics Analysis of Domain 1 of HCV-Core Protein: Iran. International Journal of Peptide Research and Therapeutics, 2019: p. 1-18.
- Behzad, D., H. Tayebeh, and H. Zahra, Interaction of Human Herpesvirus 8 Viral Interleukin-6 with Human Interleukin-6 Receptor Using In silico Approach: The Potential Role in HHV-8 Pathogenesis. Current Proteomics, 2019. 16: p. 1-1.
- Sadeghi, L., et al., HIV-1 Drug Resistance Profiles for the HIV Protease and Reverse Transcriptase Gene in Patients Receiving Combination Therapy in Tehran, Iran. Infectious Disorders-Drug Targets (Formerly Current Drug Targets-Infectious Disorders), 2018. 18(3): p. 241-248.
- Gol Mohammadi, R., et al., Drug-Resistant HIV-1 RT Gene Mutations in Patients under Treatment with Antiretroviral Drugs (HAART) in Iran. Medical Laboratory Journal, 2015. 9(1): p. 1-8.
- Farrokhi, M., et al., HIV drug resistance among naïve HIV-infected patients in Iran. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences, 2019. 24.
- Farrokhi, M., et al., Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. Iranian journal of public health, 2017. 46(9): p. 1256.
- Mohraz, M., et al., Evaluation of Acquired HIV Drug Resistance among People Living with HIV Who Have Taken Antiretroviral Therapy for 9–15 Months in 14 Triangular Clinics in Iran, 2015–2016. Intervirology, 2018. 61(6): p. 292-300.
- Davarpanah, M.A., et al., Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran. Archives of virology, 2018. 163(1): p. 99-104.
- Baesi, K., et al., Phylogeny and drug resistance of HIV PR gene among HIV patients receiving RT inhibitors in Iran. Asian Pacific Journal of Tropical Biomedicine, 2016. 6(5): p. 451-454.
- Baesi, K., et al., Subtype classification of Iranian HIV-1 sequences registered in the HIV databases, 2006-2013. PloS one, 2014. 9(9): p. e105098.
- Rolland, M. and K. Modjarrad, Multiple co-circulating HIV-1 subtypes in the Middle East and North Africa. AIDS (London, England), 2015. 29(11): p. 1417.
- Naderi, H., et al., Molecular and phylogenetic analysis of HIV-1 variants circulating among injecting drug users in Mashhad-Iran. Infectious agents and cancer, 2006. 1(1): p. 4.
- Baesi, K., et al., Drug resistance profile and subtyping of HIV-1 RT gene in Iranian patients under treatment. 2012.
- Sarrami‐Forooshani, R., et al., Molecular analysis and phylogenetic characterization of HIV in Iran. Journal of medical virology, 2006. 78(7): p. 853-863.