Role of Proviral HIV-1 DNA Genotyping for People Living with HIV (PLWH) Who Had Low-Level Viremia While Receiving Antiretroviral Therapy

Abstract

Objective

To analyze the antiretroviral resistance in people living with HIV (PLWH) who developed low-level viremia (LLV) during antiretroviral therapy (ART) via sequencing of their HIV-1 proviral DNA and RNA and comparisons of their proviral DNA genotyping data with their past and synchronous RNA genotyping data.

Patients and Methods

PLWH with LLV while receiving ART for 6 months or longer from January 2020 to September 2021 were included. HIV-1 proviral DNA and RNA were extracted from white-blood cells and concentrated plasma by ultracentrifugation, respectively, and HIV-1 pol gene fragments were amplified and sequenced. The concordance in the detection of resistance-associated mutations (RAMs) were examined between proviral DNA vs past RNA genotyping and proviral DNA vs synchronous RNA genotyping.

Results

Of the 150 PLWH with LLV, 117 proviral DNA pol sequences detected in 105 PLWH were successfully amplified and RAMs were present in 27.6% and the rate of RAMs conferring low-level or greater resistance to antiretrovirals examined was 17.1%. Fifty-six and 57 PLWH had results of past and synchronous RNA genotyping, respectively, for comparisons with those of proviral DNA genotyping; and the concordance rates were 76.8% and 75.4%, respectively. However, proviral DNA genotyping lost than gained partial information on antiretroviral resistance compared with past or synchronous RNA genotyping.

Conclusion

We found that the concordance between proviral DNA and past and synchronous RNA genotyping was moderate. Proviral DNA genotyping lost than gained more information on antiretroviral resistance compared with past or synchronous RNA genotyping. To optimize ART in PLWH with LLV, antiretroviral resistance profile should be interpreted in combination with proviral DNA and RNA genotyping and a comprehensive review of previous treatment history.

Keywords:

• genotypic resistance testing
• resistance-associated mutation
• nucleoside reverse-transcriptase inhibitor
• non-nucleoside reverse-transcriptase inhibitor
• protease inhibitor

Acknowledgment

We thank Supriya Mahajan for designing our subject and revising the manuscript.

Disclosure

The authors report no conflicts of interest in this work. The abstract of this paper was presented at the HIV Glasgow 2022 as a poster with interim findings. The poster’s abstract was published in “Poster Abstracts” in Journal of the International AIDS society: https://hivglasgow.org/wp-content/uploads/2023/01/P125_Lv_Final-Poster.pdf.

Additional information

Funding

This work was supported by the Beijing Municipal of Science and Technology Major Project (Z211100002921003 to L.D.), Beijing Natural Science Foundation (7222092 to L.D.), Capital’s Funds for Health Improvement and Research (CFH2022-1G-3015 to R.X.) and Fengtai District Health System Research Project (2020-106 to A.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.