HIV coreceptor tropism among patients with newly diagnosed infection

Abstract

Introduction: Coreceptor tropism is the ability of human immunodeficiency virus (HIV) to use CCR5 or CXCR4 coreceptor to enter the host cell. Tropism depends on the structure of the surface glycoprotein, involved in binding molecules to receptor and coreceptor. Viruses that CCR5use are named R5, viruses that CXCR4 use are X4-tropic, and dual/mixed (DM) viruses use either of the two. During early stages of HIV infection,R5 strains are usually present and with the progression of HIV disease, frequency of X4 occurs. Aim: The aim of the study was to analyze the coreceptor tropism in newly diagnosed HIV infected patients. Material and methods: The study group included 26 patients with newly diagnosed HIV infection, in the hospital care from 2010 to 2012 at the Clinic for Infectious and Tropical diseases of the Clinical Center of Serbia. Upon RNA isolation from plasma, PCR amplification and DNA sequencing of the V3 loop of the env gene were performed. The sequences were used for prediction of the coreceptor tropism, using the Geno2pheno bioinformatics algorithms. Results: R5 and X4 tropism were detected in 21/26 (81%) and 5/26 (19%) patients, respectively. Five out of twenty-six patients (19.2%) were in the C3 clinical stadium of the disease, and all of them were infected with R5-tropic virus. Fourteen out of twenty-five patients (56%) were late presenters of HIV infection, where 12 (86%) of them were infected with R5-tropic virus. Conclusion: Our results imply that the majority of HIV strains in patients, with newly diagnosed infection in Serbia, are characterized by R5 tropism. However, the prevalence of X4 strains is not negligible, indicating late presentation of newly diagnosed patients, but also possibly implying increased virulence of the circulating strains. Considering that CCR5 antagonists would not be effective in 19% of studied patients, the prediction of coreceptor tropism is undoubtedly very important.