RESEARCH PAPER
Drug-selective pressure effect on HIV integrase mutations in antiretroviral naïve and experienced patients
1
Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran
2
Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
3
Department of Microbial Biotechnology, Faculty of Biological Science, Tehran North Branch, Islamic Azad University, Tehran, Iran
4
Department of Infectious Diseases and Tropical Medicine, Tehran University of Medical Sciences, Tehran, Iran
5
Department of Microbiology, Kerman Branch, Islamic Azad University, Kerman, Iran
Submission date: 2021-06-05
Final revision date: 2021-08-23
Acceptance date: 2021-08-26
Publication date: 2023-04-28
HIV & AIDS Review 2023;22(2):99-103
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Resistance to antiretroviral drugs is a serious problem often related to selective drug-induced pressure and sub-optimal drug dosing. This study aimed to investigate drug resistance-associated mutations in human immunodeficiency virus type 1 (HIV-1) integrase gene caused by the drug pressure of reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs).
Material and methods:
For this purpose, RNA of 50 HIV-infected patients (25 drug-naïve patients and 25 patients under antiretroviral therapy [INI naive]) was extracted and one step RT-nested PCR was carried out on HIV integrase (IN). Then, gene sequences were analyzed to determine sub-types and antiretroviral resistance-associated mutations (RAMs).
Results:
Phylogenetic analysis revealed that recombinant sub-type CRF35-AD was the most prevalent in all patients (87.2%), followed by A1 sub-type (12.8%). Among the 25 ART-experienced patients, two mutations (N155I, G163R) associated with resistance to integrase inhibitors (INI) were found. Among the 25 naïve patients, several polymorphisms were observed, which was also lower in this group than in the ART group.
Conclusions:
The results of this study indicated that the integrase mutations can be caused by the effect of selective pressure induced by antiviral agents, such as RTIs and PIs. Therefore, examination of the integrase drug resistance mutations is recommended before starting treatment in Iran.
Resistance to antiretroviral drugs is a serious problem often related to selective drug-induced pressure and sub-optimal drug dosing. This study aimed to investigate drug resistance-associated mutations in human immunodeficiency virus type 1 (HIV-1) integrase gene caused by the drug pressure of reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs).
Material and methods:
For this purpose, RNA of 50 HIV-infected patients (25 drug-naïve patients and 25 patients under antiretroviral therapy [INI naive]) was extracted and one step RT-nested PCR was carried out on HIV integrase (IN). Then, gene sequences were analyzed to determine sub-types and antiretroviral resistance-associated mutations (RAMs).
Results:
Phylogenetic analysis revealed that recombinant sub-type CRF35-AD was the most prevalent in all patients (87.2%), followed by A1 sub-type (12.8%). Among the 25 ART-experienced patients, two mutations (N155I, G163R) associated with resistance to integrase inhibitors (INI) were found. Among the 25 naïve patients, several polymorphisms were observed, which was also lower in this group than in the ART group.
Conclusions:
The results of this study indicated that the integrase mutations can be caused by the effect of selective pressure induced by antiviral agents, such as RTIs and PIs. Therefore, examination of the integrase drug resistance mutations is recommended before starting treatment in Iran.
REFERENCES (24)
1.
Hamers RL, Schuurman R, Sigaloff KC, et al. Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study. Lancet Infect Dis 2012; 12: 307-317.
2.
Aghokeng AF, Kouanfack C, Eymard‐Duvernay S, et al. Virological outcome and patterns of HIV‐1 drug resistance in patients with 36 months’ antiretroviral therapy experience in Cameroon. J Int AIDS Soc 2013; 16: 18004. doi: 10.7448/IAS.16.1.18004.
3.
Cortez KJ, Maldarelli F. Clinical management of HIV drug resistance. Viruses 2011; 3: 347-378.
4.
Alaeus A, Lidman K, Björkman A, et al. Similar rate of disease progression among individuals infected with HIV-1 genetic subtypes AD. AIDS 1999; 13: 901-907.
5.
Frater AJ, Dunn DT, Beardall AJ, et al. Comparative response of African HIV-1-infected individuals to highly active antiretroviral therapy. AIDS 2002; 16: 1139-1146.
6.
Paydary K, Khaghani P, Emamzadeh-Fard S, et al. The emergence of drug resistant HIV variants and novel anti-retroviral therapy. Asian Pacific J Trop Biomed 2013; 3: 515-522.
7.
Alinaghi SA, Rasoolinejad M, Najafi Z, et al. Drug resistance patterns in HIV patients with virologic failure in Iran. Arch Clin Infect Dis 2019; 14: e96531. doi: 10.5812/archcid.96531.
8.
Gräf T, Passaes CP, Ferreira LG, et al. HIV-1 genetic diversity and drug resistance among treatment naïve patients from Southern Brazil: an association of HIV-1 subtypes with exposure categories. J Clin Virol 2011; 51: 186-191.
9.
Raimundo SM, Yang HM, Venturino E, Massad E. Modeling the emergence of HIV-1 drug resistance resulting from antiretroviral therapy: Insights from theoretical and numerical studies. Biosystems 2012; 108: 1-13.
10.
Zhao K, Kang W, Liu Q, et al. Genotypes and transmitted drug resistance among treatment-naive HIV-1-infected patients in a northwestern province, China: trends from 2003 to 2013. PLoS One 2014; 9: e109821. doi: 10.1371/journal.pone.0109821.
12.
World Health Organization. Surveillance of HIV drug resistance in populations initiating antiretroviral therapy (pre-treatment HIV drug resistance): concept note; 2014. Available at: https://apps.who.int/iris/hand....
13.
Rhee SY, Gonzales MJ, Kantor R, et al. Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucl Acids Res 2003; 31: 298-303.
14.
Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med 2006; 354: 251-260.
15.
Baesi K, Moallemi S, Farrokhi M, et al. Subtype classification of Iranian HIV-1 sequences registered in the HIV databases, 2006-2013. PLoS One 2014; 9: e105098. doi: 10.1371/journal.pone.0105098.
16.
Hirsch MS, Günthard HF, Schapiro JM, et al. Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Clin Infect Dis 2008; 47: 266-285.
17.
Russell JS, Chibo D, Kaye MB, et al. Prevalence of transmitted HIV drug resistance since the availability of highly active antiretroviral therapy. Communicable diseases intelligence quarterly report 2009; 33: 216-220.
18.
Booth CL, Geretti AM. Prevalence and determinants of transmitted antiretroviral drug resistance in HIV-1 infection. J Antimicrob Chemother 2007; 59: 1047-1056.
19.
Palma AC, Araujo F, Duque V, et al. Molecular epidemiology and prevalence of drug resistance-associated mutations in newly diagnosed HIV-1 patients in Portugal. Infect Genet Evol 2007; 7: 391-398.
20.
Mantovani NP, Azevedo RG, Rabelato JT, et al. Analysis of transmitted resistance to raltegravir and selective pressure among HIV-1-infected patients on a failing HAART in Sao Paulo, Brazil. J Clin Microbiol 2012; 50: 2122-2125.
21.
Johnson VA, Brun-Vézinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1: 2007. Top HIV Med 2007; 15: 119-125.
22.
Grover D, Copas A, Green H, et al. What is the risk of mortality following diagnosis of multidrug-resistant HIV-1? J Antimicrob Chemother 2008; 61: 705-713.
23.
Pantaleo G, Graziosi C, Fauci AS. The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993; 328: 327-335.
24.
Ceccherini-Silberstein F, Malet I, Fabeni L, et al. Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors. J Antimicrob Chemother 2010; 65: 2305-2318.
Share
RELATED ARTICLE
| eISSN: | 1732-2707 |
| ISSN: | 1730-1270 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
