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Quantitative Transmitted Drug Resistance (TDR) Variation in Acute/Recently Infected Men who have Sex with Men (MSM) Chinese HIV Patient Cohort

Lili Dai, Supriya D Mahajan, Donald L Sykes, Bindukumar Nair, Stanley A Schwartz, Chiu-Bin Hsiao, Hao Wu and Ning Li

Transmitted drug resistance (TDR) is an ongoing public health problem in HIV disease treatment and increases the risk of virologic failure following combination anti-retroviral therapy (cART) initiation. Current HIV treatment guidelines recommend resistance testing at entry into HIV care and at cART initiation. In this study, we longitudinally observed 10 acute/recently infected patients for 24-51 months. In addition to calculating the replacement rate of TDR measured by bulk population sequencing, High-throughput sequencing (HTS) was used to detect the minority mutations and quantify the variation of each TDR mutations during the follow-up. We compared the predictions of virus sensitivity to each drug by bulk population sequencing alone or by the combined sequencing with bulk population sequencing and HTS, which was analyzed with their virologic response after 6 months antiretroviral therapy. Our observations provided insights into the significance of low-frequency HIV-1 drug resistance mutations in acute/recently infected patients, and whether or not TDR are likely to revert, or persist as minority species or be stable. This study not only provides valuable data on TDR prevalence but also has important implications for the clinical management of these patients.