The Dominance of CRF01_AE and the Emergence of Drug Resistance Mutations Among Antiretroviral Therapy-Experienced, HIV-1-infected Individuals in Medan, Indonesia

Authors

  • Dwi Wahyu Indriati Department of Health, Faculty of Vocational Studies, Universitas Airlangga, Surabaya, Indonesia
  • Adiana Mutamsari Witaningrum Indonesia-Japan Collaborative Research Centre for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
  • M Qushai Yunifiar Indonesia-Japan Collaborative Research Centre for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
  • Siti Qamariyah Khairunisa Indonesia-Japan Collaborative Research Centre for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
  • Shuhei Ueda Department of Public Health, Kobe University Graduate School of Health Sciences, Hyogo, Japan
  • Tomohiro Kotaki Department of Public Health, Kobe University Graduate School of Health Sciences, Hyogo, Japan
  • Nasronudin Nasronudin Indonesia-Japan Collaborative Research Centre for Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
  • Masanori Kameoka Kobe University Graduate School of Health Sciences http://orcid.org/0000-0001-5525-9915

Keywords:

HIV-1, CRF01_AE, antiretroviral therapy, drug resistance, Medan

Abstract

Background: human immunodeficiency virus type 1 (HIV-1) infection is a serious public health threat worldwide. Medan is one example of big cities in Indonesia with a high prevalence of HIV-1 infection; however, quite a limited study had conducted for detecting the circulation of HIV-1 subtypes in Medan. In addition, a serious factor that can implicate the treatment of HIV-1-infected individuals is the emergence of drug resistance mutations. Thus, the information on HIV-1 infection is important to improve the treatment for infected individuals. Methods: sixty-seven antiretroviral therapy-experienced, HIV-1-infected individuals were recruited for this study. HIV-1 pol genes encoding protease (PR genes) and reverse transcriptase (RT gene), as well as env and gag genes, were amplified from DNA derived from peripheral blood samples. HIV-1 subtyping was conducted to study the dominant HIV-1 subtype circulating in the region. In addition, the emergence of drug resistance mutations was analyzed based on the guidelines published by the International Antiviral Society-United States of America (IAS-USA). Results: the dominant HIV-1 subtype found in Medan was CRF01_AE (77.6%). In addition, another subtype and recombinant viruses such as recombinants between CRF01_AE and subtype B (12.2%), subtype B (4.1%), and CRF02_AG (4.1%) were also found. Drug resistance-associated major mutations were found in 21.6% (8/37) of RT genes and 3.1% (1/32) of PR genes studied. Conclusion:our study showed that the dominant subtype found in ART-experienced, HIV-1-infected individuals residing in Medan was CRF01_AE. The emergence of drug resistance mutations in RT and PR genes indicated the importance to monitor the prevalence of drug resistance mutations among HIV-1-infected individuals in Medan. 

Author Biography

Masanori Kameoka, Kobe University Graduate School of Health Sciences

Professor, Department of Public Health

References

RI DPKK. Laporan perkembangan HIV AIDS dan PIMS di Indonesia. 2018. Available from http://icjr.or.id/data/wp-content/uploads/2019/08/Penanggulangan-HIV-dalam-Ancaman-R-KUHP.pdf.

World Health Organization (WHO). Update of first and second line antiretroviral regimens. WHO. 2019. Available from https://apps.who.int/iris/bitstream/handle/10665/325892/WHO-CDS-HIV-19.15-eng.pdf?ua=1.

Hong SY, Nachega JB, Kelley K, et al. The global status of HIV drug resistance: clinical and public-health approaches for detection, treatment and prevention. Infect Disord Drug Targets. 2011;11(2):124–33.

Hosseinipour MC, Gupta RK, Van Zyl G, et al. Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings. J Infect Dis. 2013;207 Suppl 2:S49–56.

Takuva S, Louwagie G, Zuma K, et al. Durability of first line antiretroviral therapy: Reasons and predictive factors for modifications in a Swaziland Cohort. J Antivirals Antiretrovir. 2012;4(1):014–20.

Indriati DW, Kotaki T, Khairunisa SQ, et al. Appearance of drug resistance mutations among the dominant HIV-1 subtype, CRF01_AE in Maumere, Indonesia. Curr HIV Res. 2018;16(2):158-66.

Khairunisa S, Kotaki T, Witaningrum AM, et al. Appearance of drug resistance-associated mutations in human immunodeficiency virus type 1 protease and reverse transcriptase derived from drug-treated Indonesian patients. AIDS Res Human retroviruses. 2015;31(2):255–9.

Merati TP, Ryan CE, Spelmen T, et al. CRF01-AE dominates the HIV-1 epidemic in Indonesia. Sex Health. 2012;9(5):414–21.

Wensing AM, Calvez V, Ceccherini-Silberstein F, et al. 2019 update of the drug resistance mutations in HIV-1. Top Antivir Med. 2019;27(3):111-21.

Porter KR, Mascola JR, Hupudio H, et al. Genetic, antigenic and serologic characterization of human immunodeficiency virus type 1 from Indonesia. J Acquir Immune Defic Syndr. 1997;14(1):1-6.

Witaningrum AM, Khairunisa SQ, Ueda S, et al. Viral subtyping of HIV-1 derived from infected, drug-naive individuals in Jakarta, Indonesia. 2018 IOP Conf Ser: Mater Sci Eng. 2018;434:012321.

Sahbandar IN, Takahashi K, Djoerban Z, et al. Current HIV type 1 molecular epidemiology profile and identification of unique recombinant forms in Jakarta, Indonesia. AIDS Res Hum Retroviruses. 2009;25(7):637–46.

Khairunisa SQ, Masyeni S, Witaningrum AM, et al. Genotypic characterization of human immunodeficiency virus type 1 isolated in Bali, Indonesia in 2016. HIV AIDS Rev. 2018;17(2):81-90.

Merati TP, Ryan CE, Spelmen T, et al. CRF01_AE dominates the HIV-1 epidemic in Indonesia. Sex Health. 2012;9(5):414–21.

Kotaki T, Khairunisa SQ, Sukartiningrum SD, et al. High Prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia. PLoS ONE. 2013;8(12):e82645.

Indriati DW, Kamasawa N, Matsui K, et al. Quantitative localization of Cav2.1 (P/Q-type) voltage-dependent calcium channels in Purkinje cells: somatodendritic gradient and distinct somatic coclustering with calcium-activated potassium channels. J Neurosci. 2013;33(8):3668–78.

Khairunisa SQ, Ueda S, Witaningrum AM, et al. Genotypic characterization of human immunodeficiency virus type 1 prevalent in Kepulauan Riau, Indonesia. AIDS Res Hum Retroviruses. 2018;34(6):555-60.

Ueda S, Witaningrum AM, Khairunisa SQ, et al. Genetic diversity and drug resistance of HIV-1 circulating in North Sulawesi, Indonesia. AIDS Res Hum Retroviruses. 2018;35(4):407–13.

Choi DJ, Dube S, Spicer TP, et al. HIV type 1 isolate Z321, the strain used to make a therapeutic HIV type 1 immunogen, is intersubtype recombinant. AIDS Res Hum Retroviruses. 1997;13(4):357–61.

Cornelissen M, Van Den Burg R, Zorgdrager F, et al. Spread of distinct human immunodeficiency virus type 1 AG recombinant lineages in Africa. J Gen Virol. 2000;81(2):515–23.

Dragic T, Litwin V, Allaway GP, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996;381(6584):667–73.

Feng Y, Broder CC, Kennedy PE, et al. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996;272(5263):872–7.

Koot M, Keet IP, Vos AH, et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med. 1993;118(9):681–8.

Karlsson A, Parsmyr K, Sandstrom E, et al. MT-2 cell tropism as prognostic marker for disease progression in human immunodeficiency virus type 1 infection. J Clin Microbiol. 1994;32(2):364–70.

Esbjörnsson J, Månsson F, Martínez-Arias W, et al. Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa. Retrovirology. 2010;7:1–13.

Bhusal N, Sutthent R, Horthongkham N, et al. Prevalence of HIV-1 subtypes and antiretroviral drug resistance mutations in Nepal. Curr HIV Res. 2016;14(6):517-24.

Luo XL, Mo LD, Su GS, et al. Incidence and types of HIV-1 drug resistance mutation among patients failing first-line antiretroviral therapy. J Pharmacol Sci. 2019;139(4):275–9.

Iemwimangsa N, Pasomsub E, Sukasem C, et al. Surveillance of HIV-1 drug-resistance mutations in Thailand from 1999 to 2014. Southeast Asian J Trop Med Public Health. 2017;48(2):271–81.

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Published

2020-12-28

How to Cite

Indriati, D. W., Witaningrum, A. M., Yunifiar, M. Q., Khairunisa, S. Q., Ueda, S., Kotaki, T., Nasronudin, N., & Kameoka, M. (2020). The Dominance of CRF01_AE and the Emergence of Drug Resistance Mutations Among Antiretroviral Therapy-Experienced, HIV-1-infected Individuals in Medan, Indonesia. Acta Medica Indonesiana, 52(4), 366. Retrieved from http://www.actamedindones.org/index.php/ijim/article/view/1429