The Emergence of HIV-1 Transmitted Drug Resistance Mutations Among Antiretroviral Therapy-naive Individuals in Buleleng, Bali, Indonesia

Authors

  • Ni Luh Ayu Megasari Universitas Airlangga
  • Devi Oktafiani Universitas Airlangga
  • Elsa Fitriana Universitas Airlangga
  • Siti Qamariyah Khairunisa Universitas Airlangga
  • Tomohiro Kotaki Kobe University Graduate School of Health Sciences
  • Shuhei Ueda Kobe University Graduate School of Health Sciences
  • Nasronudin Nasronudin Universitas Airlangga
  • Soetjipto Soetjipto soetjiptojtbr@sby.centrin.net.id
  • Masanori Kameoka Department of Public Health, Kobe University Graduate School of Health Sciences, Hyogo, Japan Center for Infectious Diseases, Kobe University Graduate School of Medicine, Hyogo, Japan. http://orcid.org/0000-0001-5525-9915

Keywords:

HIV-1, CRF01_AE, Bali, antiretroviral therapy (ART), transmitted drug resistance (TDR)

Abstract

Background: the global scale-up of antiretroviral therapy (ART) is the primary factor contributing to the decline in deaths from acquired immune deficiency syndrome (AIDS)-related illnesses. However, the emergence of transmitted drug resistance (TDR) compromises the effects of ART in treatment-naïve individuals, which may hinder treatment success. The present study aimed to identify the presence of TDR among treatment-naive individuals in Buleleng, Bali, which is currently ranked sixth among Indonesian provinces with the highest cumulative human immunodeficiency virus type 1 (HIV-1) infection cases. Methods: thirty-nine ART-naive individuals in Buleleng Regency General Hospital were enrolled in the present study. Blood samples from participants were subjected to a genotypic analysis. Results: 28 protease (PR) and 30 reverse transcriptase (RT) genes were successfully amplified and sequenced from 37 samples. HIV-1 subtyping revealed CRF01_AE as the dominant circulating recombinant form in the region. No TDR for PR inhibitors was detected; however, TDR for RT inhibitors was identified in five out of 30 samples (16.7%). Conclusion: these results indicate the emergence of TDR among ART-naive individuals in Buleleng, Bali. This issue warrants serious consideration because TDR may hamper treatment success and reduce ART efficacy among newly diagnosed individuals. Continuous surveillance with a larger sample size is necessary to monitor TDR among ART-naive individuals.

Author Biographies

Ni Luh Ayu Megasari, Universitas Airlangga

Graduate student, Faculty of Medicine

Devi Oktafiani, Universitas Airlangga

Faculty of Medicine

Elsa Fitriana, Universitas Airlangga

Faculty of Medicine

Siti Qamariyah Khairunisa, Universitas Airlangga

Researcher, Institute of Tropical Disease

Tomohiro Kotaki, Kobe University Graduate School of Health Sciences

Assistant Professor, Department of Public Health

Shuhei Ueda, Kobe University Graduate School of Health Sciences

Graduate student, Department of Public Health

Nasronudin Nasronudin, Universitas Airlangga

Professor, Faculty of Medicine

Soetjipto Soetjipto, soetjiptojtbr@sby.centrin.net.id

Professor, Faculty of Medicine

Masanori Kameoka, Department of Public Health, Kobe University Graduate School of Health Sciences, Hyogo, Japan Center for Infectious Diseases, Kobe University Graduate School of Medicine, Hyogo, Japan.

Professor, Department of Public Health

References

Joint United Nations Programme on HIV/AIDS (UNAIDS). UNAIDS Data 2018 [Internet]. 2018. Available from: www.unaids.org/sites/default/files/media_asset/unaids-data-2018_en.pdf.

HIV-CAUSAL Collaboration. Ray M, Logan R, Sterne JAC, et al. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS [Internet]. 2010 Jan 2;24(1):123–37.

Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med [Internet]. 2011;365(6):493–505.

Direktorat Jenderal Pencegahan dan Pengendalian Penyakit Kementerian Kesehatan RI (Ditjen P2P Kemenkes RI). Laporan Situasi Perkembangan HIV-AIDS & PIMS di Indonesia Januari-Desember 2017 [Internet]. 2018. Available from: http://siha.depkes.go.id/portal/files_upload/Laporan_HIV_AIDS_TW_4_Tahun_2017__1_.pdf.

Hemelaar J. The origin and diversity of the HIV-1 pandemic. Trends Mol Med [Internet]. 2012;18(3):182–92.

Khairunisa SQ, 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 Hum Retroviruses [Internet]. 2015;31(2):255–9.

Yunifiar MQ, Kotaki T, Witaningrum AM, et al. Sero- and molecular epidemiology of HIV-1 in Papua Province, Indonesia. Acta Med Indones [Internet]. 2017;49(3):205–14.

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 [Internet]. 2018;34(6):555–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29589465.

Kotaki T, Khairunisa SQ, Witaningrum AM, et al. HIV-1 transmitted drug resistance mutations among antiretroviral therapy-Naïve individuals in Surabaya, Indonesia. AIDS Res Ther [Internet]. 2015;12:5.

Witaningrum AM, Kotaki T, Khairunisa SQ, et al. Genotypic characterization of human immunodeficiency virus type 1 derived from antiretroviral therapy-naive individuals residing in Sorong, West Papua. AIDS Res Hum Retroviruses [Internet]. 2016;32(8):812–7.

Kementerian Kesehatan Republik Indonesia. Peraturan Menteri Kesehatan Republik Indonesia Nomor 87 Tahun 2014 tentang Pedoman Pengobatan Antiretroviral [Internet]. 2014. Available from: siha.depkes.go.id/portal/files_upload/Buku_Permenkes_ARV_Cetak.pdf.

Wittkop L, Günthard HF, de Wolf F, et al. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. Lancet Infect Dis [Internet]. 2011;11(5):363–71.

Wensing AM, Calvez V, Günthard HF, et al. 2017 update of the drug resistance mutations in HIV-1. Top Antivir Med [Internet]. 24(4):132–3.

Yang W-L, Kouyos R, Scherrer AU, et al. Assessing the paradox between transmitted and acquired HIV type 1 drug resistance mutations in the Swiss HIV cohort study from 1998 to 2012. J Infect Dis [Internet]. 2015;212(1):28–38.

Bertagnolio S, Perno CF, Vella S, Pillay D. The impact of HIV drug resistance on the selection of first- and second-line ART in resource-limited settings. J Infect Dis [Internet]. 2013;207 Suppl:S45-8.

Utama IGBR. Strategi menuju pariwisata Bali yang berkualitas. J Kaji Bali. 2013;03(02):69–90.

Megasari NLA, Oktafiani D, Ana EF, et al. Genotypic characterization of human immunodeficiency virus type 1 isolated from antiretroviral treatment-experienced individuals in Buleleng Regency, Bali, Indonesia [published online ahead of print May 21, 2019]. AIDS Res Hum Retroviruses. doi:10.1089/aid.2019.0058.

Siepel AC, Halpern AL, Macken C, Korber BT. A computer program designed to screen rapidly for HIV type 1 intersubtype recombinant sequences. AIDS Res Hum Retroviruses [Internet]. 1995;11(11):1413–6.

Bulla I, Schultz A-K, Meinicke P. Improving hidden Markov models for classification of human immunodeficiency virus-1 subtypes through linear classifier learning. Stat Appl Genet Mol Biol [Internet]. 2012;11(1):Article 1.

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

Trinh QM, Nguyen HL, Nguyen VN, Nguyen TVA, Sintchenko V, Marais BJ. Tuberculosis and HIV co-infection-focus on the Asia-Pacific region. Int J Infect Dis [Internet]. 2015;32:170–8.

Tadege M. Time to death predictors of HIV/AIDS infected patients on antiretroviral therapy in Ethiopia. BMC Res Notes [Internet]. 2018;11(1):761.

Masiira B, Baisley K, Mayanja BN, Kazooba P, Maher D, Kaleebu P. Mortality and its predictors among antiretroviral therapy naïve HIV-infected individuals with CD4 cell count ≥350 cells/mm3 compared to the general population: data from a population-based prospective HIV cohort in Uganda. Glob Health Action [Internet]. 2014;7:21843.

Naidoo K, Yende-Zuma N, Augustine S. A retrospective cohort study of body mass index and survival in HIV infected patients with and without TB co-infection. Infect Dis poverty [Internet]. 2018;7(1):35.

Martinez SS, Campa A, Bussmann H, et al. Effect of BMI and fat mass on HIV disease progression in HIV-infected, antiretroviral treatment-naïve adults in Botswana. Br J Nutr [Internet]. 2016;115(12):2114–21.

Sharma A, Hoover DR, Shi Q, et al. Relationship between body mass index and mortality in HIV-infected HAART users in the women’s interagency HIV study. PLoS One [Internet]. 2015;10(12):e0143740.

World Health Organization. World Health Organization Global Strategy for the Surveillance and Monitoring of HIV Drug Resistance [Internet]. 2012. Available from: https://apps.who.int/iris/bitstream/handle/10665/77349/9789241504768_eng?sequence=1.

Downloads

Published

2019-11-07

How to Cite

Megasari, N. L. A., Oktafiani, D., Fitriana, E., Khairunisa, S. Q., Kotaki, T., Ueda, S., Nasronudin, N., Soetjipto, S., & Kameoka, M. (2019). The Emergence of HIV-1 Transmitted Drug Resistance Mutations Among Antiretroviral Therapy-naive Individuals in Buleleng, Bali, Indonesia. Acta Medica Indonesiana, 51(3), 197. Retrieved from https://www.actamedindones.org/index.php/ijim/article/view/1149

Issue

Vol. 51 No. 3 (2019): Acta Medica Indonesiana

Section

ORIGINAL ARTICLE

License

Copyright

The authors who publish in this journal agree to the following requirements:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a  Creative Commons Attribution 4.0 International License (CC BY 4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
  2. Authors can enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) before and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. (See The Effect of Open Access)

Privacy Statement

The names and email addresses entered in this journal site will be used exclusively for the stated purposes of this journal and will not be made available for any other purpose or to any other party.