Molecular Antiretroviral Resistance Markers of Human Immunodeficiency Virus-1 of CRF01_AE Subtype in Bali, Indonesia

Abstract

Background: Molecular epidemiological study of human immunodeficiency virus drugresistant (HIVDR) markers is challenging in areas where the dominant subtype is non-B.

Objective: Here we provide molecular data for HIVDR in the CRF01_AE subtype in Bali, Indonesia.

Method: Seventy patients were enrolled in this study and grouped into treatment failure and treatment naïve groups. The full-length pol gene was amplified using nested reverse transcriptase polymerase chain reaction and the product was then sequenced. The readable sequence was then subjected to Stanford HIV Drug Resistance Database genotyping.

Results: We found that clinical classification was in accordance with the presence of HIVDR markers in the pol gene. Independent of therapy history, the treatment failure group showed resistance markers against nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI), ranging from 72%-100% of patients. Only a small proportion of naïve patients harbored HIV with drug resistance markers to NNRTI. No protease inhibitor-resistant marker was found in either patient group. Molecular marker mutations, which were found in more than 50% of treatment failure patients, were M184V (100%), T215A/Y/F (88.2%), D67N/G (76.5%), and M41L (58.8%).

Conclusion: The protocol used in this study to determine genetic markers of HIVDR based on subtype B can be applied for the rapid determination of resistance of the CRF01_AE subtype. All patients with progressive clinical signs and increased viral load should be recommended to undergo second-line treatment of the ARV regimen.

Keywords: Bali; CRF01_AE; Human Immunodeficiency Virus (HIV); naïve; nucleoside reverse transcriptase inhibitors (NRTI); treatment failure..

Fig. (1)

Percentage of HIVDR genotype of HIV-1 of CRF01_AE subtype to various Nucleoside Reverse Transcriptase Inhibitor (NRTI) and Non-Nucleoside Reverse Transcriptase Inhibitor (NRTI) in treatment failure and naïve patient groups in Bali, Indonesia 2008 – 2010. Grey blocks: treatment failure group; Black blocks: naïve group; NRTI: lamivudine (3TC), Abacavir (ABC), Zidovudine (AZT), Stavudine (D4T), Didanosine (DDI), Emtricitabine (FTC), and Tenofovir (TDF); NNRTI: Delavirdine (DLV), Efavirenz (EFV), Etravirine (ETR), Nevirapine (NVP).

Fig. (2)

Percentage of HIV-1 of CRF01_AE subtype in treatment failure and naïve patient groups in Bali, Indonesia 2008 – 2010, with deduced amino-acid substitutions that generate HIVDR genotype to NRTI and NNRTI. Treatment failure: above the axis; naïve: below the axis; HIVDR genotype to NRTI: unfilled bars; HIVDR genotype to NNRTI: filled bars. The numbering was annotated by The Stanford HIV Drug Resistance Database genotyping (https://hivdb.stanford.edu).