Hemodynamic variations in resting-state cerebral functional networks between Tibetan and Han male athletes assessed by fNIRS.

CRF01_AE was the first known circulating recombinant form of HIV-1. Initially detected among people living with HIV-1 with heterosexual exposure and intravenous drug use (IDU) in the southwest provinces of China, CRF01_AE rapidly spread throughout the country (). Previous evidence has suggested that CRF01_AE was more pathogenic than other subtypes in Asia. Specifically, CRF01_AE was associated with faster progression from estimated seroconversion to AIDS, higher plasma viral load, higher HIV-1 DNA level, faster CD4 T-cell count loss, and shorter median survival (). Despite sustained viral suppression under antiretroviral therapy (ART), CRF01_AE-infected patients were more likely to face suboptimal immune restoration (). The epidemic patterns of CRF01_AE in China were driven by multiple phylogenetic clusters(). These distinct CRF01_AE clusters circulated among different high-risk populations. Clusters 1, 2, and 3 were prevalent among heterosexuals and IDU, whereas clusters 4 and 5 were primarily associated with men who have sex with men (MSM) (, ). Notably, these CRF01_AE clusters also exhibited divergent pathogenic characteristics. Previous studies reported distinct phenotypic evolution between clusters 4 and 5 despite both widely circulating among MSM populations (, ). Infection with cluster 4 was associated with more pronounced CD4 T-cell depletion compared with cluster 5, and even under effective ART, individuals infected with cluster 4 showed poorer immune restoration than those infected with cluster 5. Among these CRF01_AE clusters circulating in China, cluster 4 exhibits the highest genetic diversity and is uniquely divided into two well-supported sub-clusters, designated 4a and 4b, as confirmed by high-resolution phylogenetic analyses (). Feng et al. first reported that cluster 4a comprised viruses exclusively from MSM in northern China, whereas cluster 4b contained strains sampled from non-MSM or individuals with unknown risk in eastern and southern provinces, indicating distinct underlying transmission networks within cluster 4 (). More recent work by Dai et al. reported that individuals infected with clusters 4a and 4b typically presented with extremely low baseline CD4 T-cell counts (median ~30–40 cells/µL) and a high prevalence of predicted CXCR4 tropism, features associated with more advanced disease and poorer immune prognosis (). In the same setting, cluster 4b carried pretreatment drug-resistance mutations more frequently than 4a, especially V179D and S68G (). Taken together, these findings indicate that clusters 4a and 4b already differ in their epidemiological and virological characteristics, raising the possibility that they may also diverge in clinical behavior, particularly with respect to immune reconstitution under ART. To address this knowledge gap, we conducted a retrospective longitudinal cohort study to compare immune reconstitution efficacy and virological features between patients infected with clusters 4a and 4b.