Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China

Abstract

Since the implementation of the “treat all” policy in China in 2016, there have been few data on the prevalence of transmitted drug resistance (TDR) in China. In this study, we describe TDR in patients newly diagnosed with human immunodeficiency virus (HIV) infection between 2016 and 2019 in Shenyang city, China. Demographic information and plasma samples from all newly reported HIV-infected individuals in Shenyang from 2016 to 2019 were collected. The HIV pol gene was amplified and sequenced for subtyping and TDR. The spread of TDR was analyzed by inferring an HIV molecular network based on pairwise genetic distance. In total, 2,882 sequences including CRF01_AE (2019/2,882, 70.0%), CRF07_BC (526/2,882, 18.3%), subtype B (132/2,882, 4.6%), and other subtypes (205/2,882, 7.1%) were obtained. The overall prevalence of TDR was 9.1% [95% confidence interval (CI): 8.1–10.2%]; the prevalence of TDR in each subtype in descending order was CRF07_BC [14.6% (95% CI: 11.7–18.0%)], subtype B [9.1% (95% CI: 4.8–15.3%)], CRF01_AE [7.9% (95% CI: 6.7–9.1%)], and other sequences [7.3% (95% CI: 4.2–11.8%)]. TDR mutations detected in more than 10 cases were Q58E (n = 51), M46ILV (n = 46), K103N (n = 26), E138AGKQ (n = 25), K103R/V179D (n = 20), and A98G (n = 12). Molecular network analysis revealed three CRF07_BC clusters with TDR [two with Q58E (29/29) and one with K103N (10/19)]; and five CRF01_AE clusters with TDR [two with M46L (6/6), one with A98G (4/4), one with E138A (3/3), and one with K103R/V179D (3/3)]. In the TDR clusters, 96.4% (53/55) of individuals were men who have sex with men (MSM). These results indicate that TDR is moderately prevalent in Shenyang (5–15%) and that TDR strains are mainly transmitted among MSM, providing precise targets for interventions in China.

Molecular transmission network of pretreatment drug resistance among human immunodeficiency virus-positive individuals and the impact of virological failure on those who received antiretroviral therapy in China

“…Among CRF07_BC strains with PDR, 52.8% (59/114) were within the network and distributed in ten clusters, indicating that the risk for CRF07_BC cluster growth should be monitored. Similar results were observed in some epidemic areas of China, indicating that drug-resistant HIV strains are transmitted among HIV-positive individuals ( 10 , 32 ).…”

Genetic characterization of HIV-1 viruses among antiretroviral therapy failure individuals in Suzhou City, China

“…In this study, at least 8 subtypes/CRFs were identi ed. The subtypes/CRFs distribution of HIV-1 in Suzhou City is similar to that in other areas according to previously studies [22][23][24][25], with CRF01_AE accounting for the majority, followed by CRF07_BC, subtype B and other subtypes. However, some other surveys in China showed different results, such as that in Yunnan province [26] and Minority Area [27].…”

Antiretroviral therapy initiation within 7 and 8–30 days post-HIV diagnosis demonstrates similar benefits in resource-limited settings

“…The molecular networks of the three major subtypes [CRF01_AE; CRF07_BC; and B (92.9%)] was inferred [ 10 ]. The third quartile of the number of links for all individuals with links greater than 1 in the network was 4; therefore, link at least 4 was identified as the standard for high risk of transmitting HIV.…”