CRF01_AE and CRF01_AE Cluster 4 Are Associated With Poor Immune Recovery in Chinese Patients Under Combination Antiretroviral Therapy. (16th April 2020)

• Record Type: Journal Article
• Authors: Ge, Zhangwen; Feng, Yi; Li, Kang; Lv, Bowen; Zaongo, Silvere D; Sun, Jia; Liang, Yanling; Liu, Dan; Xing, Hui; Wei, Min; Ma, Ping; Shao, Yiming
• Is Part Of: Clinical infectious diseases. Volume 72:Number 10(2021)
• Page Start: 1799
• Page End: 1809
• Publication Date: 2020-04-16
• Subjects: CRF01_AE -- CRF07_BC -- genetic cluster -- immune recovery -- X4 tropism; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa380
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Human immunodeficiency virus type 1 (HIV-1) clades and clusters have different epidemic patterns and phenotypic profiles. It is unclear if they also affect patients' immune recovery (IR) in combination antiretroviral therapy (cART). Methods: We conducted a cohort study on 853 patients under cART for evaluating the impacts of viral factor on host IR. We used generalized estimating equations for factors affecting CD4 recovery, Kaplan-Meier curves for probability of achieving IR, and Cox hazards model for factors influencing IR capability. Results: Besides low baseline CD4 and old age, CRF01_AE and its cluster 4 were independently associated with lower CD4 cell level ( P ≤ .003), slower IR ( P ≤ .022), fewer patients ( P < .001), and longer time achieving IR ( P < .001), compared with CRF07_BC and CRF01_AE cluster 5. Higher percentage of CXCR4 (X4) viruses in the CRF01_AE and cluster 4–infected patients, compared with their respective counterparts ( P < .001), accounted for the poor IR in infected patients ( P < .001). Finally, we revealed that greater X4 receptor binding propensity of amino acids was exhibited in CRF01_AE clade ( P < .001) and its cluster 4 ( P ≤ .004). Conclusions: Our study demonstrates that the CRF01_AE clade and cluster are associated with poor IR in patients under cART, which is ascribed to a high proportion of viruses with X4 tropism. HIV-1 genotyping and phenotyping should be used as a surveillance tool for patients initiating cART. CCR5 inhibitors should be used with caution in regions with high prevalence of X4 viruses. Abstract : Having high CXCR4 tropism, human immunodeficiency virus type 1 (HIV-1) CRF01_AE and its cluster 4 were independent factors associated with poor immune recovery in patients under combination antiretroviral therapy (cART). Our study underlines the importance of monitoring HIV-1 clades and clusters, to maximize cART benefit.