BACKGROUND: HIV-1 viruses have the ability to use CCR5 or CXCR4 coreceptors either solely (R5 or X4) or in combination (R5X4). The CCR5 antagonists block HIV entry into the cell and are specifically active against HIV-1 R5 strains. The objectives of this study were to investigate the predicted tropism of viruses present in paired cerebrospinal fluid (CSF) and plasma in a group of 22 HIV-1-infected patients with neurological disorders and to search for eventual discordance of predicted virus tropism between both compartments. METHODS: Paired CSF and plasma samples were selected from subjects harboring neurological disorders. V3 env was amplified and bulk sequenced, and HIV-1 coreceptor usage was determined from the V3 env region sequence by Geno2Pheno and position-specific scoring matrices (PSSM) algorithms. RESULTS: The majority of subjects (19 of 22) had concordant virus predicted tropism in both compartments. All patients having R5-tropic viruses in plasma had R5-tropic viruses in CSF (17 of 22). Patients having R5X4/X4-tropic viruses in plasma could have R5X4/X4-using (2 of 22) or R5-tropic viruses (3 of 22) in CSF. The case of R5-tropic viruses in plasma and R5X4/X4-tropic viruses in CSF was never observed. CONCLUSIONS: The majority of these patients have R5-using viruses in CSF that is mainly concordant with the predicted tropism in plasma. However, R5X4/X4 tropism in plasma does not necessarily mean the same predicted tropism in CSF compartment. Then, clinical therapeutic trials testing the clinical response to the CCR5 antagonists in patients with neurological disorders could be envisaged to analyze the effects of this therapeutic class in this setting.
BACKGROUND:HIV-1 viruses have the ability to use CCR5 or CXCR4 coreceptors either solely (R5 or X4) or in combination (R5X4). The CCR5 antagonists block HIV entry into the cell and are specifically active against HIV-1 R5 strains. The objectives of this study were to investigate the predicted tropism of viruses present in paired cerebrospinal fluid (CSF) and plasma in a group of 22 HIV-1-infectedpatients with neurological disorders and to search for eventual discordance of predicted virus tropism between both compartments. METHODS: Paired CSF and plasma samples were selected from subjects harboring neurological disorders. V3 env was amplified and bulk sequenced, and HIV-1 coreceptor usage was determined from the V3 env region sequence by Geno2Pheno and position-specific scoring matrices (PSSM) algorithms. RESULTS: The majority of subjects (19 of 22) had concordant virus predicted tropism in both compartments. All patients having R5-tropic viruses in plasma had R5-tropic viruses in CSF (17 of 22). Patients having R5X4/X4-tropic viruses in plasma could have R5X4/X4-using (2 of 22) or R5-tropic viruses (3 of 22) in CSF. The case of R5-tropic viruses in plasma and R5X4/X4-tropic viruses in CSF was never observed. CONCLUSIONS: The majority of these patients have R5-using viruses in CSF that is mainly concordant with the predicted tropism in plasma. However, R5X4/X4 tropism in plasma does not necessarily mean the same predicted tropism in CSF compartment. Then, clinical therapeutic trials testing the clinical response to the CCR5 antagonists in patients with neurological disorders could be envisaged to analyze the effects of this therapeutic class in this setting.
Authors: Katlego Sojane; Richard T Kangethe; Christina C Chang; Mahomed-Yunus S Moosa; Sharon R Lewin; Martyn A French; Thumbi Ndung'u Journal: AIDS Res Hum Retroviruses Date: 2018-05-23 Impact factor: 2.205