Relevance of early detection of HIV type 1 SI/CXCR4-using viruses in vertically infected children.
The aim of the study was to investigate the prevalence and persistence of syncytium-inducing (SI) strains in HIV-1-infected children along time of infection and to evaluate the influence of antiretroviral therapy and host factors on viral tropism. This is a retrospective analysis carried out in 267 HIV-1 vertically infected children from an Argentinean cohort. The viral phenotype was screened in MT-2 cells and coreceptor usage confirmed by the GHOST cell assay. Also, CD4(+) T cell count, viral load, antiretroviral therapy, and human CCR5-Δ32 and CCR2-64I genotypes were analyzed. A high frequency of HIV-1 SI/CXCR4-using variants (22%) was found among children within the first trimester of life, reaching 46% after 10 years of infection. At acute infection, zidovudine prophylaxis did not significantly affect the proportions of SI HIV-1 strains, while their presence was favored by the CCR5(+)/Δ32 genotype. Interestingly, the majority of the early SI strains did not persist over time, probably due to a higher susceptibility to antiretroviral (ARV) treatment or immunologic pressure. At the chronic stage, SI variants emerged even in the presence of HAART reaching 36% at 120 months of infection. Also the HIV-1 SI phenotype was associated with lower CD4(+) T cell counts all along the course of infection. These findings highlight the need to evaluate the presence of SI/CXCR4 variants early at primary infection. This will make it possible to optimize the use of CCR5 inhibitors in children who are apparently carriers of the R5 virus preventing early therapeutic failure due to the reemergence of SI strains from reservoirs.
Laboratorio de Biología Celular y Retrovirus-CONICET, Hospital Nacional de Pediatría Prof. Dr. J. P. Garrahan, Buenos Aires, Argentina.
Cintia M
CM
Crudeli
Paula C
PC
Aulicino
Carlos A
CA
Rocco
Rosa
R
Bologna
Andrea
A
Mangano
Luisa
L
Sen
D001118:Argentina / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D002461:Cell Line, Transformed; D002675:Child, Preschool; D042241:Early Diagnosis; D005260:Female; D005838:Genotype; D015726:Giant Cells / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D006679:HIV Seropositivity / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D011247:Pregnancy; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology*; D012189:Retrospective Studies; D019562:Viral Load; D056189:Viral Tropism
D019302:HIV Envelope Protein gp160; D019713:Receptors, CCR5; D019718:Receptors, CXCR4