Association of X4 tropism with disease progression in antiretroviral-treated children and adolescents living with HIV/AIDS in São Paulo, Brazil

Abstract

Management of children with HIV/AIDS is specially challenging. Age-related issues do not allow for direct transposition of adult observations to this population. CXCR4 tropism has been associated with disease progression in adults. The geno2pheno web-base is a friendly tool to predict viral tropism on envelope V3 sequences, generating a false positive rate for a CXCR4 prediction. We evaluated the association of HIV-1 tropism prediction with clinical and laboratory outcome of 73 children with HIV/AIDS in São Paulo, Brazil. The CXCR4 tropism was strongly associated with a lower (nadir) CD4 documented during follow-up (p<0.0001) and with disease severity (clinical event and/or CD4 below 200cells/mm(3)) at the last observation, using commonly applied clinical cutoffs, such as (10%)FPRclonal (p=0.001). When variables obtained during follow-up are included, both treatment adherence and viral tropism show a significant association with disease severity. As for viremia suppression, 30% (22/73) were undetectable at the last observation, with only adherence strongly associated with suppression after adjustment. The study brings further support to the notion that antiretroviral treatment adherence is pivotal to management of HIV disease, but suggests that tropism prediction may provide an additional prognostic marker to monitor HIV disease in children.

Phenotypic Coreceptor Tropism in Perinatally HIV-infected Youth Failing Antiretroviral Therapy

“…In a Brazilian study of PHIV children, associations between genotypic X4-tropism, lower CD4 nadir, and disease severity (CD4 < 200 cells/mm 3 or clinical event) were also reported [21]. In contrast to other studies, we did not find an association between X4-tropism and greater number of mutations associated with NRTI, PI or NNRTI resistance [22].…”

Young adults HIV-1 infected by vertical transmission in southern Brazil – Clinical, demographic, and virological features

“…Data about CDC classification and age at HIV-1 diagnosis are similar to other Brazilian cohorts including young children, showing a common, but adverse past. 3,25–27 In this cohort, the median CD4+ cell count at last observation did not differ from pediatric studies, despite the difference in age. 25,26,29 However, CD4+ nadir was higher, and it may have been crucial to survival.…”

“…Worldwide studies evaluating HIV-1 patients infected vertically describe mostly a pediatric population, 25–27 with scarce reports about young adults and their disease progression. 3 To our knowledge this is the first Brazilian study evaluating exclusively young adults, which included more than 50% of vertical HIV infections notified from 1987 to 1999 in the region.…”

HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells

“…In most HIV-1 positive patients including adults and children, CCR5-tropic HIV-1 replicates first, while CXCR4-tropic HIV-1 appears later in the course of disease (79). However, a substantial proportion of children show rapid disease progression and mortality (80), which is associated with CXCR4 tropism (81). This may be partly because of the active role of thymus in children in the development of mature T lymphocytes, while the thymic microenvironment further enhances the CXCR4 tropism of thymocytes (82) Recent reports showed, using humanized mouse models, that infection with CCR5-tropic HIV-1 strains may result in depletion of bone marrow CD34 + cells, which was dependent on the presence of plasmacytoid dendritic cells (pDCs) (9) or associated with the expression of CXCR4 (83).…”