Abstract
The use of anti-retroviral therapy has been effective in controlling the spread of HIV-1, and has prolonged life expectancy, but this success can be affected by the emergence of drug resistance. The main goal of this study was to investigate drug resistance in the reverse transcriptase (RT), and protease (PR) genes among HIV-1 infected individuals. We systematically selected 59 HIV-1 infected individuals from Shiraz Voluntary Counseling and Testing Center (29 treatment- naïve and 30 treated). In this study intravenous drug users older than 18 were included in this study. Using specific primers, nested RT-PCR was performed on RNA extracted from patient samples. The genes targeted for RT and PCR were successfully amplified and sequenced. The sequences of these two genes were compared with mutations related to drug resistance against nucleotide reverse transcriptase inhibitors (NRTI), non-nucleotide reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) using the latest database from the International AIDS society – USA, Stanford University, and the patterns were recorded. Among treatment-naïve, the detected NRTI and NNRTI resistance mutations were V179T, V75 M and E138A. V179T causes high level resistance to Efavirenze and Nevirapin. V75 M causes intermediate resistance to Stavudine. Regarding NRTI and NNRTI resistance mutations among treated patients, the most frequent mutation (7%) was M184 V, which causes high level resistance to zidovudin and emtricitabine. The interesting result from this study was the detection of NRTI and NNRTI resistance mutations before the initiation of treatment, which signifies the transmission of resistant strains of virus between individuals. This mutation highlights the importance of drug resistance HIV-1 genotyping before commencing treatment.
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Abbreviations
- ART:
-
Ant-Retroviral Therapy
- DR:
-
Drug Resistance
- TDR:
-
Transmitted Drug Resistance
- RT:
-
Reverse Transcriptase
- NRTIs:
-
Nucleoside Reverse Transcriptase Inhibitor
- NNRTIs:
-
Non-Nucleoside Reverse Transcriptase Inhibitor
- PI:
-
Protease Inhibitors
- IDU:
-
Intravenous Drug Use
- VCT:
-
Voluntary Counseling and Testing
- AZT:
-
Zidovudine
- 3TC:
-
Lamivudine
- EFV:
-
Efavirenz
- NJ:
-
Neighbor-Joining
References
World Health Organization (2012) HIV drug resistance report. http://www.who.int/hiv/pub/drugresistance/report2012/en/
Joulaei H, Maharlouei N, Salehi M, Kazemi A, Motazedian N (2016) Nutritional status of HIV-infected patients in Fars Province, Southern Iran. J HIV AIDS Soc Serv 15(2):147–157
Clavel F, Hance AJ (2004) HIV drug resistance. N Engl J Med 350(10):1023–1035
Palma AC, Araujo F, Duque V, Borges F, Paixão MT, Camacho R (2007) Molecular epidemiology and prevalence of drugresistance-associated mutations in newly diagnosed HIV-1patients in Portugal. Infect Genet Evol 7(3):391–398 Epub 2007 Feb 8
Coffin JM (1995) HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267:483–489
Chan PA, Kantor R (2009) Transmitted drug resistance in non-subtype B HIV-1 infection. HIV Ther 3(5):447–465. doi:10.2217/hiv.09.30
Zolopa AR, Shafer RW, Warford A et al (1999) HIV-1 genotypic resistance patterns predict response to saquinavir–ritonavir therapy in patients in whom previous protease inhibitor therapy had failed. Ann Intern Med 131(11):813–821
Baesi K, Ravanshad M, Hosseini Y, Abdolbaghi MH (2012) Drug resistance profile and subtyping of HIV-1 RT gene in Iranian patients under treatment. Iran J Biotechnol 10(1):1–7
National AIDS Committee Secretariat, Ministry of Health and Medical Education Islamic Republic of Iran AIDS Progress Report (2014). http://www.unaids.org/sites/default/files/en/dataanalysis/knowyourresponse/countryprogressreports/2014countries/IRN_narrative_report_2014_en.pdf
Sarrami-Forooshani R, Das SR, Sabahi F et al (2006) Molecular analysis and phylogenetic characterization of HIV in Iran. J Med Virol 78(7):853–863
Memarnejadian A, Menbari S, Mansouri SA et al (2015) Transmitted drug resistance mutations in antiretroviral-naïve injection drug users with chronic HIV-1 infection in Iran. PLoS One 10(5):e0126955. doi:10.1371/journal.pone.0126955 (e Collection 2015)
Werb D, Mills EJ, Montaner JS, Wood E (2010) Risk of resistance to highly active antiretroviral therapy among HIV-positive injecting drug users: a meta-analysis. Lancet Infect Dis 10(7):464–469. doi:10.1016/S1473-3099(10)70097-9
Hirsch MS, Brun-Vézinet F, D’Aquila RT et al (2000) Antiretroviral drug resistance testing in adult HIV-1 infection: recommen-dations of an International AIDS Society-USA Panel. JAMA 283:2417–2426
Bennett DE, Camacho RJ, Otelea D et al (2009) Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One 4:e4724
Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24(8):1596–1599 (epub 2007 May 7)
Jahanbakhsh F, Hattori J, Matsuda M et al (2013) Prevalence of transmitted HIV drug resistance in Iran between 2010 and 2011. PLoS One 8(4):e61864. doi:10.1371/journal.pone.0061864 (print 2013)
Mousavi SM, Hamkar R, Gouya MM et al (2010) Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study. Arch Virol 155(3):329–334. doi:10.1007/s00705-009-0583-6 (Epub 2010 Jan 6)
Gupta R, Hill A, Sawyer AW, Pillay D (2008) Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Clin Infect Dis 47(5):712–722. doi:10.1086/590943
Hamkar R, Mohraz M, Lorestani S et al (2010) Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients. AIDS 24(suppl 2):S85–S91. doi:10.1097/01.aids.0000386738.32919.67
Koigi P, Ngayo MO, Khamadi S, Ngugi C, Nyamache AK (2014) HIV type 1 drug resistance patterns among patients failing first and second line antiretroviral therapy in Nairobi, Kenya. BMC Res Notes 7:890. doi:10.1186/1756-0500-7-890
McFaul K, Lim C, Jones R, Asboe D et al (2014) Transmitted antiretroviral drug resistance in treatment naïve HIV-infected persons in London in 2011 to 2013. J Int AIDS Soc 17(4 Suppl 3):19747. doi:10.7448/IAS.17.4.19747 (e Collection 2014)
Bennett DE, Bertagnolio S, Sutherland D, Gilks CF (2008) The World Health Organization’s global strategy for prevention and assessment of HIV drug resistance. Antivir Ther 13(Suppl 2):1–13
Acknowledgements
The authors would like to thank the Research Consultation Center (RCC) for their invaluable assistance in editing this article. The authors also wish to thank treatment deputy, research deputy of Shiraz University of Medical Sciences, and Mr. Vahapour for invaluable help and support.
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Our study was approved by the Ethical Committee of Shiraz University of Medical Sciences and informed written consent was taken from all patients. (Committee’s reference number: 59-5056)
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Handling editor: Li Wu.
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Davarpanah, M.A., Motazedian, N., Joulaei, H. et al. Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran. Arch Virol 163, 99–104 (2018). https://doi.org/10.1007/s00705-017-3549-0
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DOI: https://doi.org/10.1007/s00705-017-3549-0