Evidence that HIV-1 CRF01_AE is associated with low CD4+T cell count and CXCR4 co-receptor usage in recently infected young men who have sex with men (MSM) in Shanghai, China.

Men who have sex with men (MSM) have recently accounted for an alarmingly increasing proportion of HIV-1 transmission in China. In order to investigate the immune status as a result of CRF01_AE infection and CXCR4 co-receptor usage in a young Shanghai-based HIV-1-infected MSM population in Shanghai, 364 HIV-1-infected MSM with average age of 22.7 years old, newly diagnosed between Jan 2009 and Jul 2013 were analyzed for CD4+T cell count, subtyping using phylogenetic analysis, and viral co-receptor tropism using Geno2pheno and webPSSM in combination. A total of 276 individuals were identified as recently infected. Subtype assignment were as follows: 176 (63.8%) CRF01_AE, 77 (27.9%) CRF07_BC, and 23 (8.3%) subtype B. Besides, 24 second-generation recombinant strains were identified. A lower CD4+T cell count at baseline survey was observed among CRF01_AE strain-infected individuals, compared to those who were infected with CRF07_BC (P<0.01). The frequency of baseline CD4+T cell count <200 was higher and the frequency of CD4 T counts >500 lower in CRF01_AE infection than CRF07_BC infection. It is worth noting that 32.4%-40.9% of CRF01_AE strain-infected individuals were predicted to carry CXCR4-tropic viruses whereas none of CRF07_BC and subtype B were found to be as CXCR4-tropic viruses (P<0.001). As could be expected CXCR4 tropism was associated with lower CD4 T counts. This study revealed that CRF01_AE strains with high frequency of CXCR4 tropism are prevailing in the young MSM population in China and could potentially cause a severe loss of CD4+T cell count and rapid disease progression. A regular surveillance of HIV-1 subtypes, CD4+T cell count and viral co-receptor usage would be greatly beneficial for effectively monitoring disease progression, improvement of antiretroviral therapy strategy and prompt intervention of transmission.

Genetic diversity and drug resistance of human immunodeficiency virus type 1 (HIV-1) strains circulating in Shanghai.

The HIV-1 epidemic in Shanghai is rapidly increasing. To better understand the HIV-1 genetic diversity and the mutations associated with resistance to protease inhibitors (PIs) and reverse transcriptase inhibitors (RTIs), 95 antiretroviral (ARV)-treated and treatment-naive HIV-1-seropositive individuals living in Shanghai were investigated. The HIV-1 pol gene in 70 of the 95 plasma samples was successfully amplified and analyzed. The result showed that CRF01_AE predominated in Shanghai with 42.9%, followed by subtype B (10%), B' (12.9%), CRF07_BC (11.4%), CRF08_BC (10%), CRF02_AG (4.3%), G (2.9%), and K (1.4%). In addition, three new intersubtype and/or inter-CRF recombinants were detected including B'/CRF01_AE (1.4%), U/G (1.4%), and U/CRF01_AE (1.4%). The mutations conferring primary and secondary resistance to PIs were detected in 3 of 70 (4.3%) patients and the mutations conferring resistance to RTIs were identified in 12 of 70 (17.2%) patients, among whom 11 of 15 (73.3%) and 1 of 55 (1.8%) were ARV-treated and treatment-naive individuals, respectively (p < 0.01). This study reveals the emergence of genetic diversity of HIV-1 currently circulating in Shanghai. HIV-1 infection by heterosexual contact is still a major route for introduction of HIV-1 variants into this city in recent years. It is believed that this information may help to guide recommendations for diagnostic assays, vaccine design, and antiretroviral regimen strategies in China.