Viral Tropism in Human Immunodeficiency Virus Type 1-Infected Children and Adolescents in Thailand

Abstract

Background: Maraviroc, a C-C chemokine receptor 5 (CCR5) antagonist, has been used as an alternative antiretroviral drug in treatment-experienced adults and children infected by CCR5-tropic human immunodeficiency virus type 1 (HIV-1) isolates. Prior to widespread use of this drug, rates of HIV-1 coreceptor tropism and factors associated with coreceptor tropism had to be determined. Methods: HIV-1-infected individuals aged <20 years with HIV-1 viral loads >1000 RNA copies/mL who were treatment-experienced or treatment-naive were enrolled. HIV-1 coreceptor tropism was determined using a genotypic test in which V3 sequences were analyzed with GENO2PHENO version 2.5 and a false discovery rate of 5%. Results: Fifty-two HIV-1-infected patients were recruited. The median age of participants was 14.9 years (interquartile range [IQR], 8.9-16.8 years). The median CD4 cell count was 396.0 cells/μL (IQR, 72.0-630.3 cells/μL). The median HIV-1 viral load was 43 339 RNA copies/mL (IQR, 8874-197 055 copies/mL). Thirty-nine patients (75%) were treatment-experienced. The most prevalent HIV-1 subtype in this population was CRF01_AE (36 patients, 69.2%). Based on analyses of V3 loop sequences, 5 of 13 treatment-naive patients (38.5%) and 11 of 39 treatment-experienced patients (28.2%) were infected by R5 viruses, while 7 of 13 treatment-naive patients (53.8%) and 19 of 39 treatment-experienced patients (48.7%) were infected by X4 viruses. The only factor associated with the presence of X4 viruses was HIV-1 subtype CRF01_AE. Conclusions: X4-tropic viruses are associated with the CRF01_AE subtype. Hence, testing of HIV tropism should be performed before treatment with CCR5 inhibitors in children in areas where CRF01_AE predominates.