Testing genotypic and phenotypic resistance in human immunodeficiency virus type 1 isolates of clade B and other clades from children failing antiretroviral therapy.
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.
Brindeiro
Patrícia A
PA
Laboratory of Molecular Virology, Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Brindeiro
Rodrigo M
RM
Mortensen
Cláudio
C
Hertogs
Kurt
K
De Vroey
Veronique
V
Rubini
Norma P M
NP
Sion
Fernando S
FS
De Sá
Carlos A M
CA
Machado
Deisy M
DM
Succi
Regina C M
RC
Tanuri
Amilcar
A
D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015751:Genes, pol; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation; D010641:Phenotype; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease