1. Testing genotypic and phenotypic resistance in human immunodeficiency virus type 1 isolates of clade B and other clades from children failing antiretroviral therapy.
- Author
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Brindeiro PA, Brindeiro RM, Mortensen C, Hertogs K, De Vroey V, Rubini NP, Sion FS, De Sá CA, Machado DM, Succi RC, and Tanuri A
- Subjects
- Adolescent, Anti-HIV Agents pharmacology, Child, Child, Preschool, Drug Therapy, Combination, Female, Genes, pol, Genotype, HIV Infections virology, HIV Protease genetics, HIV Protease Inhibitors pharmacology, HIV Reverse Transcriptase genetics, HIV-1 enzymology, HIV-1 genetics, Humans, Male, Microbial Sensitivity Tests methods, Mutation, Phenotype, Reverse Transcriptase Inhibitors pharmacology, Treatment Failure, Anti-HIV Agents therapeutic use, Drug Resistance, Viral, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, HIV-1 classification, HIV-1 drug effects, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
The emergence of resistance to antiretroviral drugs is a major obstacle to the successful treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients. In this work, we correlate clinical and virological trends such as viral load (VL) and CD4 counts to genotypic and phenotypic antiretroviral (ARV) resistance profiles of HIV-1 isolates from the B and non-B subtypes found in vertically infected children failing ARV therapy. Plasma samples were collected from 52 vertically HIV-1-infected children failing different ARV therapies. Samples underwent HIV-1 pol sequencing and phenotyping and were clustered into subtypes by phylogenetic analysis. Clinical data from each patient were analyzed together with the resistance (genotypic and phenotypic) data obtained. Thirty-five samples were from subtype B, 10 samples were non-B (subtypes A, C, and F), and 7 were mosaic samples. There was no significant difference concerning treatment data between B and non-B clades. Prevalence of known drug resistance mutations revealed slightly significant differences among B and non-B subtypes: L10I, 21 and 64%, K20R, 13 and 43%, M36I, 34 and 100%, L63P, 76 and 36%, A71V/T, 24 and 0%, and V77I, 32 and 0%, respectively, in the protease (0.0001 = P = 0.0886), and D67N, 38 and 8%, K70R, 33 and 0%, R211K, 49 and 85%, and K219Q/E, 31 and 0%, respectively, in the reverse transcriptase (0.0256 = P = 0.0704). Significant differences were found only in secondary resistance mutations and did not reflect significant phenotypic variation between clade B and non-B.
- Published
- 2002
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