CRF01_AE and CRF01_AE Cluster 4 Are Associated With Poor Immune Recovery in Chinese Patients Under Combination Antiretroviral Therapy

et al. 2020

Sci Rep

Self Cite

To assess whether human immunodeficiency virus type 1 (HIV-1) genotype influences baseline CD4+ T lymphocyte (CD4+) cell count and mortality of patients. The study was conducted from 2014 to 2019 in Guangxi, China, and included 2845 newly diagnosed HIV patients. We used a median regression model to compare CD4+ cell counts in patients newly diagnosed with different HIV-1 genotypes, and a Cox regression model to analyze the associations between HIV-1 genotypes and mortality before and after antiretroviral treatment (ART). In newly diagnosed HIV patients, the baseline CD4+ cell counts of patients with CRF01_AE were significantly lower than those of patients with CRF07_BC, CRF08_BC, and other genotypes. Compared with CRF01_AE, patients infected with CRF07_BC (hazard ratio, 0.55; 95% CI 0.36–0.85), CRF08_BC (hazard ratio, 0.67; 95% CI 0.52–0.85), or other genotypes (hazard ratio, 0.52; 95% CI 0.29–0.94) had significantly lower mortality rates before ART. There were no significant associations between different HIV-1 genotypes and mortality after ART. HIV-1 genotype significantly influences baseline CD4+ cell count and mortality before ART in newly diagnosed HIV patients. We find no significant difference in the outcome of death after ART in patients with different HIV-1 genotypes.

Section: Discussionmentioning

confidence: 99%

Effects of HIV-1 genotype on baseline CD4+ cell count and mortality before and after antiretroviral therapy

Cao

et al. 2020

Sci Rep

Self Cite

“…Consequently, the significant difference in IR ability among the HIV patients with different genotypes could be attributed to the high proportion of X4 tropism in the CRF01_AE subtype and its cluster 1. Although this study was based on the viral tropism obtained by HIV-1 genotyping prediction, its accuracy has been verified by previous research in the same category [ 28 , 45 ].…”

Section: Discussionmentioning

confidence: 55%

“…Moreover, in the N-linked glycan site at the beginning of the V3 loop (V3 positions 6–8, HXB2 nos.301–303), the CRF01_AE cluster 1 and 2 sequences had lost the residue N/T at positions 7–8 site, which was replaced by Lysine and Isoleucine amino acids. Previous studies have shown that the preference for the CXCR4 co-receptor tropism was positively correlated with the K7, R11, R13 and K32 (HXB2 numbers K302, R306, R308 and K327) amino acid substitutions of V3 loop [ 18 , 45 ]. Therefore, this reveals a greater propensity to X4-using in CRF01_AE and its cluster 1.…”

Section: Discussionmentioning

confidence: 99%

Immune reconstruction effectiveness of combination antiretroviral therapy for HIV-1 CRF01_AE cluster 1 and 2 infected individuals

Emerging Microbes & Infections

et al. 2021

Self Cite

There are great disparities of the results in immune reconstruction (IR) of the HIV-1 infected patients during combined antiretroviral therapy (cART), due to both host polymorphisms and viral genetic subtypes. Identifying these factors and elucidating their impact on the IR could help to improve the efficacy. To study the factors influencing the IR, we conducted a 15-year retrospective cohort study of HIV-1 infected individuals under cART. The trend of CD4 + count changes was evaluated by the generalized estimating equations. Cox proportional model and propensity score matching were used to identify variables that affect the possibility of achieving IR. The tropism characteristics of virus were compared using the coreceptor binding model. In addition to baseline CD4 + counts and age implications, CRF01_AE cluster 1 was associated with a poorer probability of achieving IR than infection with cluster 2 (aHR, 1.39; 95%CI, 1.02-1.90) and other subtypes (aHR, 1.83; 95%CI, 1.31-2.56). The mean time from cART initiation to achieve IR was much longer in patients infected by CRF01_AE cluster 1 than other subtypes/sub-clusters ( P < 0.001). In-depth analysis indicated that a higher proportion of CXCR4 viruses were found in CRF01_AE clusters 1 and 2 ( P < 0.05), and showed tendency to favour CXCR4 binding to V3 signatures. This study indicated the immune restoration impairment found in patients were associated with HIV-1 CRF01_AE cluster 1, which was attributed to the high proportion of CXCR4-tropic viruses. To improve the effectiveness of cART, more efforts should be made in the early identification of HIV-1 subtype/sub-cluster and monitoring of virus phenotypes.

“…We have previously shown that CRF07_BC has a lower TDR prevalence than subtype B and CRF01_AE (1.5% vs. 4.8% vs. 5.6%) respectively 27 , 28 . Ge et al 29 and Cao et al 30 have demonstrated that CRF07_BC is associated with better immune recovery in Chinese patients undergoing antiretroviral treatment (ART) compared to that of patients infected with CRF01_AE. Taken together, these results support the hypothesis that CRF07_BC is less pathogenic than subtype B.…”

Section: Discussionmentioning

confidence: 99%

CRF07_BC is associated with slow HIV disease progression in Chinese patients

Wang

et al. 2022

Sci Rep

Self Cite

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count < 200 cells/µL) in patients with HIV subtype B, CRF01_AE, and CRF07_BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01_AE. CRF07_BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07_BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥ 65 years vs. < 18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for men who have sex with men vs. heterosexuals: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining in complexity. CRF07_BC is less pathogenic than subtype B, while CRF01_AE is as pathogenic as B.