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

Ni Luh Ayu Megasari, Devi Oktafiani, Elsa Fitriana, Siti Qamariyah Khairunisa, Tomohiro Kotaki, Shuhei Ueda, Nasronudin Nasronudin, Soetjipto Soetjipto, Masanori Kameoka


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.


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


Joint United Nations Programme on HIV/AIDS (UNAIDS). UNAIDS Data 2018 [Internet]. 2018. Available from:

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:

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:

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:

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:

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