Background HIV-1 clades and clusters have different epidemic patterns and phenotypic profiles. It is unclear if they also affect patient’s immune recovery (IR) in combined antiretroviral therapy (cART). Methods We conducted cohort study on 853 patients under cART for evaluating the impacts of viral factor on host IR. We used Generalized Estimating Equations for factor affecting CD4 recovery, Kaplan–Meier curves for the probability achieving IR and Cox hazard model for factors influencing the rate of IR. Results In addition to low baseline CD4 and old age, CRF01_AE and its cluster 4 independently associated with lower CD4 cell recovery (P≤0.003), slower rate of IR (P≤0.022), less patients (P<0.001) and longer time achieving IR (P<0.001), compared to CRF07_BC and CRF01_AE cluster 5 respectively. Higher percentage of X4 viruses was found in CRF01_AE and cluster 4 infected patients (P<0.001), compared to their respective counterparts. The X4 viruses accounted for the poor IR in patients infected by CRF01_AE (P<0.001), its cluster 4 (P<0.001) and 5 (P≤0.029). Finally, we revealed that greater X4-binding propensity amino acids was exhibited in CRF01_AE clade (P<0.001) and CRF01_AE cluster 4 (P≤0.004). Conclusions Our study demonstrates that CRF01_AE clade and its cluster 4 are associated with poor IR in Chinese patients under cART, which are ascribed to high proportion of viruses with X4 tropism. HIV-1 genotyping and phenotyping should be used as surveillance tool for patients initiating cART. CCR5 inhibitors should be used with caution in regions with high prevalence of X4 viruses.
By analyzing an unprecedentedly large, longitudinal HIV-1 CRF07_BC sequence dataset collected from China in the past two decades, we sought to build CRF07_BC lengthwise transmission networks, and understand its transmission dynamics. We divided CRF07_BC into two clusters based on phylogenetic analysis and an estimation of the pairwise genetic distance at 0.7%. Of 6,213 sequences, 3,607 (58.1%) linked to ≥1 other sequence. CRF07_BC was divided into two clusters: 07BC_O and 07BC_N. The 07BC_O is the original CRF07_BC, circulating in people who inject drugs (PWID) and heterosexuals, predominantly in southwestern and northwestern provinces of China. The 07BC_N is a new cluster, identified mostly in men having sex with men (MSM) in northern provinces of China. Bayesian analysis indicates that CRF07_BC has experienced two phases of exponential growth, which was first driven by 07BC_O then 07BC_N. Compared to 07BC_O, the proportion of the parameter of population transmission risk (TR) of 07BC_N has risen constantly. The power-law function analyses reveal that 07BC_N has increased over years with higher degree. In 07BC_N, only 13.16% of MSM were linked to other risk groups, but these links represent 41.45%, 54.25%, and 55.07% of links among heterosexual females, heterosexual males, and male PWID respectively. This study indicates that CRF07_BC has evolved into two clusters in China, and their distributions are distinct across risk groups and geographical regions. 07BC_N shows greater risk of transmission, and has gradually replaced 07BC_O. Furthermore, the results show that strengthening the MSM interventions could lower the rapidity of 07BC_N transmission in all risk groups.
Objective: Toward the limited real-world data concerning the treatment response to brand direct-acting antiviral agents (DAAs) therapy, we proposed to evaluate the efficacy and safety of DAAs for the treatment of chronic hepatitis C virus (HCV) in mainland China. Methods: In this retrospective, single-center, cohort study, all HCV-infected adult patients treated with brand DAA drugs covered by Tianjin local health insurance (Apr 2018-Sept 2019) and responding to other specific inclusion criteria were recruited. The five available DAA regimens included sofosbuvir + ribavirin (SOF + RBV), elbasvir/ grazoprevir (EBR/GZR), ombitasvir/paritaprevir/ritonavir/dasabuvir (OBV/PTV/r/DSV) ± RBV, daclatasvir + asunaprevir (DCV + ASV), and SOF + DCV ± RBV. Demographic, virologic, clinical, and adverse effects data obtained during and after DAAs treatment were collected. We evaluated the rate of sustained virological response at 12 weeks posttreatment (SVR12), the incidence of adverse effects, and assessed the factors associated with SVR12. Results: Four hundred ninety-four patients finished the treatment and completed the 12week post-treatment follow-up. The overall SVR12 rate was estimated at 96.96%. SVR rates greater than 95% were achieved in most of the HCV genotypes with the exception of GT1a (0%), GT3a (93.33%), and GT3b (88.24%). SVR12 for patients treated with DCV + ASV, EBR/GZR, OBV/PTV/r/DSV ± RBV, SOF + DCV ± RBV, and SOF + RBV for 12 or 24 weeks was 86.67%, 100%, 98.11%, 97.56%, and 95.06%, respectively. Subjects with compensated cirrhosis (92.73%) and prior treatment experience (77.78%) had significantly lower SVR rates when compared to chronic hepatitis C (98.15%) and treatment-naive (97.69%) groups. In Tianjin, the available DAA regimens were generally well-tolerated, and not a single serious adverse event was reported.
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