Rapid CD4+ T-cell decline is associated with coreceptor switch among MSM primarily infected with HIV-1 CRF01_AE in Northeast China

Abstract

Objective: CRF01_AE is the most prevalent HIV-1 subtype among MSM in China. However, the characteristics and underlying mechanism of the accelerated CD4 T-cell decline in CRF01_AE-infected MSM remain incompletely understood. Design: A long-term prospective follow-up study was conducted with 1388 MSM at risk of HIV-1 infection in Northeast China. MSM with primary HIV-1 CRF01_AE infection were identified and followed for 3-6 years to explore the determinants of rapid CD4 T-cell decline. Methods: Tropism was determined in primary infection by both single genome amplification-based genotypic prediction using four different algorithms and phenotypic determination using clinical isolates. Serial isolates were used to determine phenotype of coreceptor switch. Human leukocyte antigen genotypes and T-cell activation markers were determined. Results: Fifty-nine MSM primarily infected with HIV-1 CRF01_AE were discovered and recruited for the follow-up study. CCR5-utilizing (R5) viruses accounted for up to 98% of HIV-1 CRF01_AE infections in Northeast China. Survival analysis indicated 39.5% of the patients underwent coreceptor switch within 3 years after infection. After adjustment for other potential risk factors, linear mixed-effect models demonstrated patients experienced R5 to CXCR4-utilizing/dual-tropic (X4/DM) coreceptor switch within 3 years after infection underwent a faster CD4 T-cell decline compared to those without coreceptor switch. Conclusions: Primary HIV-1 CRF01_AE infection among MSM in Northeast China is characterized by R5 viral infection and early R5 to X4/DM coreceptor switch, which is associated with rapid CD4 T-cell decline. The findings highlight the importance of immediate treatment among the CRF01_AE-infected MSM.