Emergence of primary NNRTI resistance mutations without antiretroviral selective pressure in a HAART-treated child.
OBJECTIVE
The use of antiretrovirals (ARV) during pregnancy has drastically reduced the rate of the human immunodeficiency virus perinatal transmission (MTCT). As a consequence of widespread ARV use, transmission of drug resistant strains from mothers to their babies is increasing. Ultra-sensitive PCR techniques have permitted the quantification of minority viral populations, but little is known about the transmission of drug-resistant HIV-1 minority population in the setting of MTCT.


RESULTS
We describe the case of a female child born to an HIV-infected mother, which had not taken any ARV during the pregnancy. The child's first genotype demonstrated a minor non-nucleoside reverse transcriptase inhibitor (K101E), and during her treatment with reverse transcriptase and protease inhibitors full resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) emerged (G190A). Phenotypic/genotypic analysis of variant quasispecies through yeast TyHRT assay was conducted to characterize minority resistant viral strains circulating in both mother and child. Maximum likelihood and Bayesian MCMC phylogenetic analyses were performed with samples from the pair to assess genetic relatedness among minor viral strains. The analysis showed that the child received a minor NNRTI resistant variant, containing the mutation K101E that was present in less than 1% of the mother's quasispecies. Phylogenetic analyses have suggested common ancestry between the mother's virus strain carrying K101E with the viral sequences from the child.


CONCLUSIONS
This is the first documentation of MTCT of a minority resistant strain of HIV-1. The transmission of minor resistant variants carries the threat of emergence of multi-drug primary mutations without identified specific selective pressures.
Machado
Elizabeth S
ES
Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Afonso
Adriana O
AO
Nissley
Dwight V
DV
Lemey
Philippe
P
Cunha
Silvia M
SM
Oliveira
Ricardo H
RH
Soares
Marcelo A
MA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016049:Didanosine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000151:congenital / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020125:Mutation, Missense; D019888:Nelfinavir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010802:Phylogeny; D017354:Point Mutation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology; D012641:Selection, Genetic; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D019259:Lamivudine; D015215:Zidovudine; D019888:Nelfinavir; D016049:Didanosine