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Universal antiretroviral therapy (ART, "treat all") was recommended by the World Health Organization in 2015; however, HIV-1 transmission is still ongoing. This study characterizes the drivers of HIV transmission in the "treat all" era. Demographic and clinical information and HIV pol gene were collected from all newly diagnosed cases in Shenyang, the largest city in Northeast China, during 2016 to 2019. Molecular networks were constructed based on genetic distance and logistic regression analysis was used to assess potential transmission source characteristics. The cumulative ART coverage in Shenyang increased significantly from 77.0% (485/630) in 2016 to 93.0% (2598/2794) in 2019 (p < 0.001). Molecular networks showed that recent HIV infections linked to untreated individuals decreased from 61.6% in 2017 to 28.9% in 2019, while linking to individuals with viral suppression (VS) increased from 9.0% to 49.0% during the same time frame (p < 0.001). Undiagnosed people living with HIV (PLWH) hidden behind the links between index cases and individuals with VS were likely to be male, younger than 25 years of age, with Manchu nationality (p < 0.05). HIV transmission has declined significantly in the era of "treat all". Undiagnosed PLWH may drive HIV transmission and should be the target for early detection and intervention. [ABSTRACT FROM AUTHOR]

Molecular network analysis based on the genetic similarity of HIV-1 is increasingly used to guide targeted interventions. Nevertheless, there is a lack of experience regarding molecular network inferences and targeted interventions in combination with epidemiological information in areas with diverse epidemic strains of HIV-1.We collected 2,173 pol sequences covering 84% of the total newly diagnosed HIV-1 infections in Shenyang city, Northeast China, between 2016 and 2018. Molecular networks were constructed using the optimized genetic distance threshold for main subtypes obtained using sensitivity analysis of plausible threshold ranges. The transmission rates (TR) of each large cluster were assessed using Bayesian analyses. Molecular clusters with the characteristics of ≥5 newly diagnosed cases in 2018, high TR, injection drug users (IDUs), and transmitted drug resistance (TDR) were defined as priority clusters. Several HIV-1 subtypes were identified, with a predominance of CRF01_AE (71.0%, 1,542/2,173), followed by CRF07_BC (18.1%, 393/2,173), subtype B (4.5%, 97/2,173), other subtypes (2.6%, 56/2,173), and unique recombinant forms (3.9%, 85/2,173). The overall optimal genetic distance thresholds for CRF01_AE and CRF07_BC were both 0.007 subs/site. For subtype B, it was 0.013 subs/site. 861 (42.4%) sequences of the top three subtypes formed 239 clusters (size: 2-77 sequences), including eight large clusters (size ≥ 10 sequences). All the eight large clusters had higher TR (median TR = 52.4/100 person-years) than that of the general HIV infections in Shenyang (10.9/100 person-years). A total of ten clusters including 231 individuals were determined as priority clusters for targeted intervention, including eight large clusters (five clusters with≥5 newly diagnosed cases in 2018, one cluster with IDUs, and two clusters with TDR (K103N, Q58E/V179D), one cluster with≥5 newly diagnosed cases in 2018, and one IDUs cluster. In conclusion, a comprehensive analysis combining in-depth sampling HIV-1 molecular networks construction using subtype-specific optimal genetic distance thresholds, and baseline epidemiological information can help to identify the targets of priority intervention in an area epidemic for non-subtype B. [ABSTRACT FROM AUTHOR]