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 drug-resistant (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 Stan-ford 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 in-hibitors (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 sub-type 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.

Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

“…Due to significant genetic diversification of circulating HIV-1 strains observed over the last three decades ( 92 , 93 ), there is a need to focus vaccine design on more contemporaneous Envs, such as these RV217 founder Envs, which were isolated between 2009 and 2015 ( 36 ). Additionally, the emergence of novel CRF01_AE recombinants ( 8 , 94 – 96 ) and drug-resistant strains ( 97 – 100 ) has been reported. CRF01_AE infections appear to be rapidly expanding in certain countries and are now the dominant cause of new infections in China, Indonesia, Vietnam, and the Philippines ( 94 , 101 – 105 ).…”