Mutations linked to drug resistance, human immunodeficiency virus type 1 biologic phenotype and their association with disease progression in children receiving nucleoside reverse transcriptase inhibitors.

Published

Journal Article

BACKGROUND: Few data are available concerning the impact of antiretroviral resistance in response to antiviral therapy in children. We evaluated the development of antiretroviral genotypic resistance and clinical outcome in a subgroup of children involved in a prospective antiretroviral therapy trial (Pediatric AIDS Clinical Trials Group Protocol 152). DESIGN: We studied 26 matched case/control pairs. A case was defined as having clinical disease progression during the study period; controls did not have disease progression. Cases and controls were matched by age and CD4+ cell count at baseline. Matched pairs received treatment with zidovudine (9 pairs), didanosine (12 pairs) or combined therapy (5 pairs). Multiple codons of the reverse transcriptase coding region (41, 67, 70, 74, 151, 184, 210, 215 and 219) were analyzed. Patients were evaluated for CD4+ cell count, HIV-1 viral load and HIV-1 biologic phenotype at baseline and clinical endpoint. RESULTS: The presence of mutations associated with resistance after nucleoside antiretroviral therapy (P = 0.039) and syncytium-inducing phenotype (P = 0.031), were significantly associated with increased risk of clinical disease progression. The mean difference in HIV-1 RNA levels between cases and their matched controls after nucleoside antiretroviral therapy was 0.77 log10 copies/ml higher for cases (P = 0.003). The median difference between cases and controls for CD4+ cell count after nucleoside antiretroviral therapy was 349 cells/mm3 lower for cases (P < 0.001). CONCLUSIONS: In this small prospective study of HIV-infected children, mutations in the reverse transcriptase coding region, syncytium-inducing viral phenotype, higher HIV-1 RNA load and lower CD4+ cell count were significantly correlated with increased risk of HIV clinical disease progression.

Full Text

Duke Authors

Cited Authors

  • Englund, JA; Raskino, C; Vavro, C; Palumbo, P; Ross, LL; McKinney, R; Nikolic-Djokic, D; Colgrove, RC; Baker, CJ; Pediatric AIDS Clinical Trials Group Protocol 152 Team,

Published Date

  • January 2004

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 15 - 22

PubMed ID

  • 14743040

Pubmed Central ID

  • 14743040

International Standard Serial Number (ISSN)

  • 0891-3668

Digital Object Identifier (DOI)

  • 10.1097/01.inf.0000105105.80229.ba

Language

  • eng

Conference Location

  • United States