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

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.