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

Abstract

Shiyun Lv,1,* Lijun Sun,1,* Tongzeng Li,1,* Ruojing Bai,1 Man Dai,2,3 Ran Wang,1 Yuanyi Zhai,1 Wei Hua,1 Aixin Li,1 Ruolei Xin,2 Lili Dai1 1Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Institute for STD/AIDS Prevention and Treatment, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 3School of Public Health, Chinese Medical University, Shenyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lili Dai, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China, Tel [phone], Email [email protected] Ruolei Xin, Institute for STD/AIDS Prevention and Treatment, Beijing Center for Disease Prevention and Control, Beijing, 100013, People’s Republic of China, Tel [phone], Email [email protected]: 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

Keywords

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