HIV-1 DNA Genotypic Drug Resistance Testing Guides Antiretroviral Therapy in Patients with Low-Level Viremia.

Abstract

In 2023, we published a case study involving a 10-year-old HIV-1-infected child with low-level viremia (LLV). We showed that this child patient achieved successful viral suppression by modifying the antiretroviral therapy (ART) regimen according to the HIV-1 DNA genotypic drug resistance testing. In this study, we aimed to address whether HIV-1 DNA genotypic drug resistance testing could direct successfully virological suppression in HIV-1-infected patients experiencing persistent LLV based on evidence from a cohort study. The subjects of this study were all people living with HIV-1 who received ART and followed in the Yuexi County (Liangshan, China) from December 2010 to February 2024. From June 2021 to February 2024, a total of 10 mL of peripheral blood was collected from each subject at each follow-up and separated. HIV-1 RNA and HIV-1 DNA were quantified, followed by HIV-1 genotypic drug resistance testing. ART regimens were accordingly adjusted, while follow-up tests were performed in terms of HIV-1 RNA and DNA measurements. The prevalent HIV-1 DNA drug resistance mutations (DRMs) included M184V, K103N, K101E/P, and V108I. The primary resistance mutations observed for nucleoside reverse transcriptase inhibitor (NRTI) were against abacavir, lamivudine, and emtricitabine. For non-NRTI, the primary DRMs were associated with efavirenz and nevirapine. Five out of the six patients were subjected to regimen adjustments according to HIV-1 DNA DRMs, while one patient was continuously treated with unchanged regimen. Viral suppression was achieved in all five ART-changed cases, with observation of remarkable of HIV-1 DNA decline. The ART-unchanged case showed progressive treatment failure with drastic increase of plasma HIV-1 RNA and whole blood HIV-1 DNA. For patients with LLV, HIV-1 DNA genotypic drug resistance testing directed ART regimen considerations are highly recommended for achieving viral suppression.