Transmitted drug resistance and transmission clusters among ART-naïve HIV-1-infected individuals from 2019 to 2021 in Nanjing, China.

Abstract

Transmitted drug resistance (TDR) is an increasingly prevalent problem worldwide, which will significantly compromise the effectiveness of HIV treatments. However, in Nanjing, China, there is still a dearth of research on the prevalence and transmission of TDR among ART-naïve HIV-1-infected individuals. This study aimed to understand the prevalence and transmission of TDR in Nanjing. A total of 1,393 participants who were newly diagnosed with HIV-1 and had not received ART between January 2019 and December 2021 were enrolled in this study. HIV-1 pol gene sequence was obtained by viral RNA extraction and nested PCR amplification. Genotypes, TDR and transmission cluster analyses were conducted using phylogenetic tree, Stanford HIV database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with TDR. A total of 1,161 sequences were successfully sequenced, of which CRF07_BC (40.6%), CRF01_AE (38.4%) and CRF105_0107 (6.3%) were the main HIV-1 genotypes. The overall prevalence of TDR was 7.8%, with 2.0% to PIs, 1.0% to NRTIs, and 4.8% to NNRTIs. No sequence showed double-class resistance. Multivariate logistic regression analysis revealed that compared with CRF01_AE, subtype B (OR = 2.869, 95%CI: 1.093-7.420) and female (OR = 2.359, 95%CI: 1.182-4.707) were risk factors for TDR. Q58E was the most prevalent detected protease inhibitor (PI) -associated mutation, and V179E was the most frequently detected non-nucleoside reverse transcriptase inhibitor (NNRTI) -associated mutation. A total of 613 (52.8%) sequences were segregated into 137 clusters, ranging from 2 to 74 sequences. Among 44 individuals with TDR (48.4%) within 21 clusters, K103N/KN was the most frequent TDR-associated mutation (31.8%), followed by Q58E/QE (20.5%) and G190A (15.9%). Individuals with the same TDR-associated mutations were usually cross-linked in transmission clusters. Moreover, we identified 9 clusters in which there was a transmission relationship between drug-resistant individuals, and 4 clusters in which drug-resistant cases increased during the study period. The overall prevalence of TDR in Nanjing was at a moderate level during the past 3 years. However, nearly half of TDR individuals were included in the transmission clusters, and some drug-resistant individuals have transmitted in the clusters. Therefore, HIV drug-resistance prevention, monitoring and response efforts should be sustained and expanded to reduce the prevalence and transmission of TDR in Nanjing.