title: 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.
authors.affiliation: Division of Pediatric Infectious Diseases, Santa Casa de São Paulo Hospital, Brazil. Electronic address: flaviaja@gmail.com.
authors.forename: Flávia Jacqueline
authors.initials: FJ
authors.lastname: Almeida
authors.affiliation: Retrovirology Laboratory, Adolfo Lutz Institute, Brazil.
authors.forename: Mayra Simioni
authors.initials: MS
authors.lastname: Zaparoli
authors.affiliation: Retrovirology Laboratory, Adolfo Lutz Institute, Brazil.
authors.forename: Denise Helena
authors.initials: DH
authors.lastname: Moreira
authors.affiliation: Retrovirology Laboratory, Adolfo Lutz Institute, Brazil.
authors.forename: Jaqueline de Souza
authors.initials: Jde S
authors.lastname: Cavalcanti
authors.affiliation: Retrovirology Laboratory, Adolfo Lutz Institute, Brazil.
authors.forename: Rosangela
authors.initials: R
authors.lastname: Rodrigues
authors.affiliation: Division of Pediatric Infectious Diseases, Santa Casa de São Paulo Hospital, Brazil.
authors.forename: Eitan Naaman
authors.initials: EN
authors.lastname: Berezin
authors.affiliation: Retrovirology Laboratory, Adolfo Lutz Institute, Brazil.
authors.forename: João Leandro de Paula
authors.initials: JL
authors.lastname: Ferreira
authors.affiliation: Division of Pediatric Infectious Diseases, Santa Casa de São Paulo Hospital, Brazil.
authors.forename: Marco Aurélio Palazzi
authors.initials: MA
authors.lastname: Sáfadi
authors.affiliation: Retrovirology Laboratory, Adolfo Lutz Institute, Brazil.
authors.forename: Luis Fernando de Macedo
authors.initials: LF
authors.lastname: Brígido
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019718:Receptors, CXCR4 / Q000502:physiology*; D019562:Viral Load; D056189:Viral Tropism / Q000502:physiology*
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D019718:Receptors, CXCR4
keywords: Children; Disease progression; HIV-1; Viral tropism