Abstract
This study reconstructed molecular networks of human immunodeficiency virus (HIV) transmission history in an area affected by an epidemic of multiple HIV-1 subtypes and assessed the efficacy of strengthened early antiretroviral therapy (ART) and regular interventions in preventing HIV spread. We collected demographic and clinical data of 2221 treatment-naïve HIV-1–infected patients in a long-term cohort in Shenyang, Northeast China, between 2008 and 2016. HIV pol gene sequencing was performed and molecular networks of CRF01_AE, CRF07_BC, and subtype B were inferred using HIV-TRACE with separate optimized genetic distance threshold. We identified 168 clusters containing ≥ 2 cases among CRF01_AE-, CRF07_BC-, and subtype B-infected cases, including 13 large clusters (≥ 10 cases). Individuals in large clusters were characterized by younger age, homosexual behavior, more recent infection, higher CD4 counts, and delayed/no ART (P < 0.001). The dynamics of large clusters were estimated by proportional detection rate (PDR), cluster growth predictor, and effective reproductive number (Re). Most large clusters showed decreased or stable during the study period, indicating that expansion was slowing. The proportion of newly diagnosed cases in large clusters declined from 30 to 8% between 2008 and 2016, coinciding with an increase in early ART within 6 months after diagnosis from 24 to 79%, supporting the effectiveness of strengthened early ART and continuous regular interventions. In conclusion, molecular network analyses can thus be useful for evaluating the efficacy of interventions in epidemics with a complex HIV profile.
Highlights
The rapid evolution of human immunodeficiency virus (HIV) leaves measurable footprints in the viral genome that can be used for epidemic surveillance by phylogenetic analysis (Hassan et al, 2017)
A total of 2221 individuals who were newly diagnosed with HIV infection between January 2008 and December 2016 were included in the study
We evaluated factors associated with clustering in these individuals and found that those in large clusters had distinct characteristics from individuals in the other two groups (Table 1), and were more likely to be male (85.8 vs 77.7% in small/medium clusters and 71.6% in non-clustered individuals; P < 0.001) and younger (29.4% of individuals < 25 years of age vs. 20.7% and 18.6%; P < 0.001); have Recent HIV infection (RHI) status (33.4% vs 30.9% and 22.8%; P < 0.001); report men who have sex with men (MSM) contact as their main risk behavior (94.5% vs 85.4% and 84.2%; P < 0.001); and have a high CD4 + cell count (18% with ≥ 500 cells/μl vs 14% and 11.6%; P < 0.001)
Summary
The rapid evolution of human immunodeficiency virus (HIV) leaves measurable footprints in the viral genome that can be used for epidemic surveillance by phylogenetic analysis (Hassan et al, 2017). Several local and national studies conducted in recent years have monitored the dynamics of HIV molecular clusters and evaluated their expansion speed (Chan et al, 2015; Mehta et al, 2018; Ragonnet-Cronin et al, 2018; Wertheim et al, 2018; Jovanovic et al, 2019; Dennis et al, 2020) Most of these studies focused on areas with only subtype B or C HIV-1 epidemics, and few local studies have reconstructed HIV transmission history in an area with multiple HIV subtypes, which may be more complicated because of the variable transmission dynamics and evolution rates of different HIV-1 strains in the population
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