Correlation between Antiretroviral Therapy Responses and Resistance to First-Line Reverse Transcriptase Inhibitors in People Living with HIV-1 Experiencing Virological Failure in South Sulawesi, Indonesia.

Abstract

Introduction: The effectiveness of antiretroviral therapy (ART) in treating HIV is in-fluenced by the clinical response of patients, which, in turn, impacts the development of drug resistance. This study aimed to assess the correlation between clinical treatment response and resistance to first-line reverse transcriptase inhibitors in HIV patients receiving treatment for ≤12 and >12 months in South Sulawesi, a province in Indonesia.

Methods: In this cross-sectional study, 36 people living with HIV (PLHIV) experiencing viro-logical failure (VF) were sampled from HIV services in the province from August 2022 to January 2023. HIV-1 viral RNAs were extracted, sequenced, and analyzed for drug sensitivity and re-sistance classification using the Stanford University HIV Drug Resistance Database (HIVdb) ac-cording to World Health Organization (WHO) recommendations, determining resistance levels and HIV subtypes. Phylogenetic analysis of PR-RT sequences (~1200 base pairs) was performed using the Muscle program and MEGA11 software, utilizing the neighbor-joining method with the Kimura two-parameter model.

Results: Genotyping of plasma samples revealed that a significant proportion of patients exhib-ited mutations associated with resistance to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) (48.6% and 51.4%, respectively). Clinical response indica-tors, such as initial body mass index and occurrence of opportunistic infections, were found to correlate with specific drug resistance, highlighting the importance of monitoring treatment re-sponse. Moreover, virologic response showed strong associations with resistance to specific drugs, suggesting the need for tailored therapeutic approaches. Patient behaviors related to trans-mission risk factors were also found to be linked to resistance levels, underscoring the multifac-torial nature of resistance development.

Conclusion: Overall, this study underscores the importance of considering treatment response in managing HIV and suggests implications for optimizing therapy regimens to mitigate resistance emergence.