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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]

The transmission of Unique Recombinant Forms (URFs) has complicated the molecular epidemic of HIV-1. This increasing genetic diversity has implications for prevention surveillance, diagnosis, and vaccine design. In this study, we characterized the HIV-1 URFs from 135 newly diagnosed HIV-1 infected cases between 2016 and 2020 in Shenyang, northeast China and analyzed the evolutionary relationship of them by phylogenetic and recombination approaches. Among 135 URFs, we found that the CRF01_AE/CRF07_BC recombinants were the most common (81.5%, 110/135), followed by CRF01_AE/B (11.9%, 16/135), B/C (3.7%, 5/135), and others (3.0%, 4/135). 94.8% (128/135) of patients infected by URFs were through homosexual contact. Among 110 URFs_0107, 60 (54.5%) formed 11 subclusters (branch support value = 1) and shared the consistent recombination structure, respectively. Four subclusters have caused small-scale spread among different high-risk populations. Although the recombination structures of URFs_0107 are various, the hotspots of recombinants gathered between position 2,508 and 2,627 (relative to the HXB2 position). Moreover, the CRF07_BC and CRF01AE fragments of URFs_0107 were mainly derived from the MSM population. In brief, our results reveal the complex recombinant modes and the high transmission risk of URFs_0107, which calls for more attention on the new URFs_0107 monitoring and strict control in the areas led by homosexual transmission route. [ABSTRACT FROM AUTHOR]

Background: To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China.Methods: Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay.Results: A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%).Conclusions: The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city. [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]

Background: Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, whether LLV increases the risk of virologic failure (VF) is controversial because of the non-uniform definitions of LLV and VF.Methods: A long-term first line regimen ART cohort from 2002 to 2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses.Results: A total of 2155 HIV-1 infected participants were included; of these, 38.7% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HLB) showed higher risk of VF (hazards ratios, HRHLLV = 5.93, and HRHLB = 2.84, p <  0.05 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR = 3.49, p = 0.002), nadir baseline CD4 + T cell counts below 200 cells/mm3 (aOR = 1.78, p = 0.011), Manchu (aOR = 2.03, p = 0.003), ART over 60 months (aOR = 1.81, p = 0.004), AZT + 3TC + NVP (aOR = 2.26, p <  0.001) or DDI-based regimen (aOR = 9.96, p = 0.002), and subtype B' infection (aOR = 8.22, p = 0.001).Conclusions: In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B' infection might also predict the occurrence of high-risk LLV. [ABSTRACT FROM AUTHOR]