HIV coreceptor tropism in antiretroviral treatment-naive patients newly diagnosed at a late stage of HIV infection

Abstract

A substantial number of HIV infections worldwide are diagnosed at a late stage of disease. Mortality in late presenters is high, and their treatment is a specific challenge. We have determined the relative proportions of HIV-1 strains of different coreceptor tropism (CRT) in this group of patients and investigated the impact of CRT on progression markers such as CD4 cell counts and viral load, and on the clinical presentation of the patients. Plasma samples from 50 treatment-naive patients with a late HIV diagnosis (CD4 cell counts of <200 cells/microl at the time of diagnosis) were analyzed. HIV strains were sequenced, and for CRT determination, the internet tool geno2pheno[coreceptor] was used, with a 20% false-positive rate as the cutoff. Differences in progression markers, patient characteristics and HIV subtype distribution between the R5-infected and X4/DM-infected patient groups were evaluated statistically. CRT predictions indicated that 62% of the patients had only R5-tropic strains. CRT was not associated with CD4 cell counts or viral load at the time of diagnosis. Only in very late presenters (CD4 cell counts <50 cells/microl) was there a significant difference in disease stage at the time of presentation, showing that patients with R5 more often were at Centers for Disease Control and Prevention stage C3 compared with those with X4/DM strains (P = 0.04). A substantial number of patients diagnosed at a late stage of HIV-1 infection may be infected exclusively with R5-tropic virus strains, making this specific patient group a possible candidate for coreceptor antagonist treatment.