Prevalence of drug resistance mutations in HIV-infected individuals with low-level viraemia under combination antiretroviral therapy: An observational study in a tertiary hospital in Northern Taiwan, 2017-19

Background: Effective ART is crucial for combating the HIV pandemic. Clinically, plasma viral load monitoring to achieve virological suppression is the guide for an optimal ART. The presence of low-level viraemia (LLV) below the definition level of virological failure is a risk factor for ART failure. However, there is no treatment consensus over LLV yet, mainly due to the limitation of standard HIV-RNA genotyping and the resultant insufficient understanding of LLV characteristics. Objectives: To better profile drug resistance mutations (DRMs) and the associated factors in cases experiencing LLV. Methods: A prospective observational study was conducted from 2017 to 2019. HIV-DNA was used as an alternative to HIV-RNA for HIV genotyping coupled with deep sequencing for ART-naive and ART-failure cases, as well as those with LLV. Results: Eighty-one ART-naive, 18 ART-failure and 16 LLV cases received HIV genotyping in the study. Three-quarters (12/16) of cases experiencing LLV harboured DRMs. Cases with LLV had higher prevalence of DRMs to NNRTIs than the ART-naive group (69% versus 20%, P < 0.001), but lower DRM prevalence to NRTIs than the ART-failure group (25% versus 61%, P < 0.001). Approximately half of the LLV cases had issues of suboptimal ART compliance/ART interruption, and 68.8% (11/16) did not display drug resistance to their ART at the time of LLV. Conclusions: HIV DRM profiles in LLV cases were significantly different to those in ART-naive and ART-failure cases. Approaches to consolidate ART compliance and early exploration of potential ART resistance may be needed for cases experiencing LLV episodes.