Viral load as a risk factor of reverse transcriptase inhibitor drug resistance mutation in antiretroviral-treated people living with HIV/AIDS
Article Sidebar
Main Article Content
Abstract
Background
The human immunodeficiency virus type 1 (HIV-1) is a major contagion faced by the population of Indonesia. The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). The aim of this study was to determine the association between CD4 count, CD4 count changes, viral load, adherence to therapy, and therapy history in the presence of DRM in people living with HIV/AIDS (PLWHA).
Methods
This was a cross-sectional study involving 269 adults who underwent antiretroviral (ARV) therapy for at least 6 months. The frequencies of DRM and polymorphisms were measured by partial amplification of the reverse transcriptase (RT) gene using RT-nested PCR on samples with viral loads of >1000 copies/mL. Sequencing was performed using the Sanger method, and edited by BioEdit. The edited sequences were submitted to http://hivdb.stanford.edu for DRM determination. Respondents’ medical data, CD4 count, viral load, and DRM were analyzed by simple and multiple logistic regression.
Results
The multiple logistic regression analysis showed a significant association of CD4 count (aOR=12.47; 95% CI: 1.45 -107.39; p=0.023) and viral load at the time of study (aOR=29.56; 95% CI: 3.47-251.52; p=0.002) with the presence of DRM in respondents. ARV substitution history was not associated with the presence of DRM. There were 17 respondents (6.3%) carrying HIV-1 DRM, with M184V/I (11 sequences) as the most frequent pattern of NRTI resistance, and K103 (9 sequences) as that of NNRTI resistance.
Conclusion
This study demonstrated that viral load at the time of the study was the most influential determinant factor for the presence of DRM in PLWHA.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.
References
Menteri Kesehatan RI. Rencana aksi nasional pengendalian HIV-AIDS tahun 2015-2019. Jakarta: Kementerian Kesehatan RI; 2015.
Pemerintah Provinsi Papua Barat Dinas Kesehatan. Profil kesehatan Papua Barat; 2018.
Abecasis AB, Wensing AMJ, Paraskevis D, et al. HIV-1 Subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics. Retrovirology 2013;10:1–13. DOI: 10.1186/1742-4690-10-7.
Melikian GL, Rhee SY, Varghese V, et al. Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. J Antimicrob Chemother 2014;69:12–20. DOI: 10.1093/jac/dkt316.
Castro H, Pillay D, Cane P, et al. Persistence of HIV-1 transmitted drug resistance mutations. J Infect Dis 2013;208:1459–63. DOI: 10.1093/infdis/jit345.
Quashie PK, Mesplede T, Han YS, et al. Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. J Virol 2012;86:2696–705. DOI: 10.1128/jvi.06591-11.
Krishnan KM, Amsavathani SK. Polymorphisms of HIV RT gene among the ART naive native drug exposed rural PLHA. J Glob Infect Dis 2012;4:110–3. DOI: 10.4103/0974-777X.9677.5.
Palumbo PJ, Fogel JM, Hudelson SE, et al. HIV drug resistance in adults receiving early versus delayed antiretroviral therapy: HPTN 052. J Acquir Immune Defic Syndr 2018;77:484–91. DOI: 10.1097/QAI.0000000000001623.
Bock P, James A, Nikuze A, et al. Baseline CD4 count and adherence to antiretroviral therapy: a systematic review and meta-analysis. J Acquir Immune Defic Syndr 2016;73:514–21. DOI: 10.1097/QAI.0000000000001092.
Haberer JE, Sabin L, Amico KR, et al. Improving antiretroviral therapy adherence in resource-limited settings at scale: a discussion of interventions and recommendations. J Int AIDS Soc 2017;20:21371–85. DOI: 10.7448/IAS.20.1. 21371.
Da W, Li X, Qiao S, et al. Evaluation of self-report adherence measures and their associations with detectable viral load among people living with HIV (PLHIV) in China. PLoS One 2018;13e0203032. DOI: 10.1371/journal.pone.0203032.
Ekong E, Ndembi N, Okonkwo P, et al. Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria. AIDS Res Ther 2020;17:1–8. DOI: 10.1186/s12981-020-0261-z.
Hutapea HML, Fitriana E, Natalia EI, et al. Gambaran kasus mutasi terkait resistensi antiretroviral pada orang dengan HIV-AIDS (ODHA) di tiga Kabupaten / Kota di Provinsi Papua. Bul Penelit Kesehat 2018;46:199–206. DOI: 10.22435/bpk.v46i3.902.
Deletsu SD, Maina EK, Quaye O, Ampofo WK, Awandare GA, Bonney EY. High resistance to reverse transcriptase inhibitors among persons infected with human immunodeficiency virus type 1 subtype circulating recombinant form 02_AG in Ghana and on antiretroviral therapy. Medicine (Baltimore): 2020;99:e18777. DOI: 10.1097/MD.0000000000018777.
Hong SY, Nachega JB, Kelley K, Bertagnolio S, Marconi VC, Jordan MR. The global status of HIV drug resistance: clinical and public-health approaches for detection, treatment and prevention. Infect Disord Drug Targets 2011;11:124–33.
Lodi S, Günthard HF, Dunn D, et al. Effect of immediate initiation of antiretroviral treatment on the risk of acquired HIV drug resistance. AIDS 2018;32:327–35. DOI: 10.1097/QAD.000000000000 1692.
Schultze A, Paredes R, Sabin C, et al. The association between detected drug resistance mutations and CD4+ T-cell decline in HIV-positive individuals maintained on a failing treatment regimen. Antivir Ther 2018;23:105–16. DOI: 10.3851/IMP3178.
Badan Pusat Statistik Provinsi Papua Barat. Hasil sensus penduduk 2020 Provinsi Papua Barat. Manokwari: Berita Resmi Statistik; 2020.
Kementerian Kesehatan RI. Direktorat Jenderal Pengendalian Penyakit Pusat Data dan Informasi. HIV AIDS . Kesehatan 2020. Jakarta: Pusat Data dan Informasi;2020.
Ministry of Health Republic of Indonesia. HIV epidemiology review, Indonesia 2016. Jakarta : Directorate General of Disease Prevention and Control; 2017.
Schultze A, Torti C, Cozzi-Lepri A, et al. for the European Transmitted Drug Resistance collaboration (EU-TDR). The effect of primary drug resistance on CD4R cell decline and the viral load set-point in HIV-positive individuals before the start of antiretroviral therapy. AIDS 2019; 33:315–26. DOI:10.1097/QAD.0000000000002046.
Lu X, Zhao H, Zhang Y, et al. HIV 1 drug resistant mutations and related risk factors among HIV 1 positive individuals experiencing treatment failure in Hebei Province, China. AIDS Res Ther 2017;14:4. DOI 10.1186/s12981-017-0133-3.
Rossouw TM, Feucht UD, Melikian G, et al. Factors associated with the development of drug resistance mutations in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy in South Africa. PLoS ONE 2015;107: e0133452. https://doi.org/10.1371/journal.pone. 0133452.
Widiyanti M, Oktavian A, Wibowo HA, et al. Identifikasi genotipe human immunodeficiency virus –1 (HIV-1) pada orang dengan HIV/AIDS (ODHA) di Kota Jayapura Provinsi Papua. Yayapura: Perpustakaan Badan Litbang Kesehatan;2017.
World Health Organization. WHO manual for HIV drug resistance testing using dried blood spot specimens; 3rd ed. Geneva: World Health Organization; 2020.
Hoffman J, Van Griensven J, Colebunders R, et al. Role of the CD4 count in HIV management. HIV Ther 2010;4:27–39.
Wilson EMP, Sereti I. Immune restoration after antiretroviral therapy: the pitfalls of hasty or incomplete repairs. Immunol Rev 2013;254:343–54. DOI: 10.3174/ajnr.A1256.
Etta EM, Mavhandu L, Manhaeve C, et al. High level of HIV-1 drug resistance mutations in patients with unsuppressed viral loads in rural northern South Africa. AIDS Res Ther 2017;14:1–12. DOI: 10.1186/s12981-017-0161-z.
Girerd-Genessay I, Baratin D, Ferry T, Chidiac C, Ronin V, Vanhems P. Higher HIV RNA viral load in recent patients with symptomatic acute HIV infection in Lyon University hospitals. PLoS One 2016;11:1–6. DOI: 10.1371/journal.pone.0146978.
World Health Organization. Clinical guidelines: antiretroviral therapy. In: Consolidated Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Geneva: World Health Organization ;2016. p. 72–190.
Memiah P, Shumba C, Etienne-mesubi M, et al. The effect of depressive symptoms and CD4 count on adherence to highly active antiretroviral therapy in sub-Saharan Africa. JIAPAC 2014;13:346–52. DOI: 10.1177/2325957413503368.
Chen Y, Chen K, Kalichman SC. Barriers to HIV medication adherence as a function of regimen simplification. Ann Behav Med 2017;176:139–48. DOI: 10.1007/s12160-016-9827-3.
DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC). Guidelines for the use of antiretroviral agents in adults and aAdolescents. Department of Health and Human Services; 2018.
Arguello JR, Noyola DE, Centro C. Prevalence of drug resistance mutations in protease, reverse transcriptase and integrase genes of North-Central Mexico HIV isolates. AIDS Res Hum Retroviruses 2017;52:1–29. DOI: 10.1089/AID. 2017.0257.
Tanuma J, Hachiya A, Ishigaki K, et al. Impact of CRF01_AE-specific polymorphic mutations G335D and A371V in the connection subdomain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on susceptibility to nucleoside RT inhibitors. Microbes Infect 2010;12:1170–7. DOI: 10.1016/j.micinf.2010.08.003.