High prevalence of X4/DM-tropic variants in children and adolescents infected with HIV-1 by vertical transmission.

ABSTRACT

BACKGROUND: We studied HIV coreceptor tropism in vertically HIV-infected children and adolescents with the objective of predicting the proportion of children and adolescents that could be treated with CCR5 (R5) antagonists. METHODS: One hundred eighteen multidrug-resistant pediatric patients (36 children and 82 adolescents) were enrolled in a cross-sectional study. Viral tropism was assessed using the new phenotypic HIV-1 tropism coreceptor assay information and Trofile. RESULTS: Of 118 antiretroviral-experienced HIV-infected children and adolescents, 49 (57.0%) had dual-tropic and 20 (23.3%) had X4-tropic viruses by tropism coreceptor assay information testing. Only 17 (19.7%) showed R5-tropic variants. HIV-1 coreceptor usage was not detectable in 32 of 118 (27%) patients. Among 24 children and 62 adolescents with tropism coreceptor assay information results, 17 (70.8%) children and 51 (82.2%) adolescents showed viruses with dual-tropic or X4-tropic variants. Additionally, Trofile (ES) was performed in 42 of 118 patients with HIV-1 RNA > 1000 copies/mL. No patient showed X4-tropic variants; dual-tropic viruses were observed in 12 (28.6%) patients. In 6 (14.3%) patients, HIV tropism could not be determined. X4-tropic variants were more common in children (P = 0.031). CD4 T cell percentage was significantly lower in children (P = 0.011) and adolescents (P = 0.027) with R5-tropic viruses than in those with X4-tropic viruses. CONCLUSIONS: The presence of X4-tropic variants in more than 80% of our cohort of antiretroviral-experienced children and adolescents with vertical HIV-1 infection indicates a very limited role for CCR5 antagonists as part of salvage regimens for highly treatment-experienced vertically HIV-1-infected patients with extensive antiretroviral drug resistance and limited treatment options.