Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina.
BACKGROUND
The aim of this study was to describe the frequency of minority populations of viruses carrying mutations K103N and M184V in drug-naive HIV type-1 (HIV-1)-infected children, and to further evaluate their effect on the selection of drug-resistant viruses within highly active antiretroviral therapy (HAART).


METHODS
Newly diagnosed vertically HIV-1-infected children were evaluated. The HIV-1 pol gene was sequenced for subtyping and antiretroviral drug resistance analysis. Standard genotypic sequencing and sequence-selective real-time PCR (SPCR) to quantify minority viral populations were used.


RESULTS
From December 2004 to July 2006, we included 35 children who were studied at baseline and during their first HAART regimen (follow-up median time 29.4 months). Of them, 82.9% were infected with intersubtype B/F recombinant variants. At baseline, all children had a drug-susceptible viral population that was studied by bulk sequencing. SPCR showed that 4 children had between 2-10% of M184V, 11 had <0.7%, 18 had no detectable mutation and 2 could not be amplified. No K103N minority populations were found. Once under HAART, children who had 2-10% of M184V at baseline further selected it in percentages >20% in less time than those with -0.1-0.6% or without minority populations (P=0.01).


CONCLUSIONS
It was shown that having 2-10% of M184V at baseline enhanced its selection in high percentages in a short time after HAART initiation. Further research regarding the presence of minority quasispecies before initiation of HAART in large paediatric populations should be undertaken to evaluate their clinical effect during HAART.
Vignoles
Moira
M
National Reference Center for AIDS, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Barboni
Graciela
G
Agosti
María R
MR
Quarleri
Jorge
J
García
Mariel K
MK
Ayala
Silvia González
SG
Salomón
Horacio
H
D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D001118:Argentina / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015751:Genes, pol; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine