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

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CRF01_AE is the most prevalent human immunodeficiency virus-1 (HIV-1) subtype among men who have sex with men (MSM) in China. However, the characteristics and underlying mechanism of the accelerated CD4+ T-cell decline in CRF01_AE-infected MSM remain incompletely understood.


A long-term prospective follow-up study was conducted with 1338 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.


Tropism was determined in primary infection by both SGA-based genotypic prediction using four different algorithms and phenotypic determination using clinical isolates. Serial isolates were used to determine phenotype of coreceptor switch. HLA genotypes and T-cell activation markers were determined.


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 subjects underwent coreceptor switch within 3 years post 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 three years post-infection underwent a faster CD4+ T-cell decline compared to those without coreceptor switch.


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.

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