Background :  HIV-1 mother-to-child-transmission (MTCT) is now <2% in most northern countries, however, widespread ART usage could be associated with an increased of ART drug resistance in this context. Our aims were to analyze prevalence and mechanism of resistance mutations acquisition at time of birth in infected newborns.

Methods:  This retrospective study was conducted among all HIV-1-infected infants born between January 1, 1997 and December 31, 2004, included in the EPF cohort and with samples available in Necker Laboratory. Genotypic resistance tests were performed on the earliest plasma (HIV-1 RNA) and cellular (HIV-1 DNA) samples. When available, mothers’ samples were also analyzed. In case of drug resistance detected in children, longitudinal study of resistance mutations was performed.

Results:  During this period, 99 among 5162 children (1.9%) born to HIV-1-seropositive mothers were infected and included in the EPF cohort. Resistance study was performed on available children and mothers samples for 53 and 25, respectively. Of the children’s samples, 38 were from infants younger than 60 days of age; 11 infants (21%) had virus with mutation associated with drug resistance. Resistance mutations to nucleoside reverse transcriptase inhibitor (NRTI) (especially zidovudine [ZDV] and lamivudine [3TC]) was detected in 8 of 11 cases (73%); to non-NRTI (NNRTI) in 1 child, to protease inhibitor (PI) in 1 child and to NRTI+NNRTI in 1 child. In 8 of the 11 cases, the same resistance mutations were detected concomitantly in HIV-1 RNA from mothers and in HIV-1 RNA and DNA from their children. This suggested that transmission of resistant viruses from mother-to-child led to early archive of resistance in the child’s cellular reservoir. Longitudinal resistance study, performed in 6 of 8 children with a median of 52 months (range 5 to 64), showed that resistance mutations persisted over time, whatever ART was use. In 3 of 11 children with resistance mutations in HIV-1 RNA, wild type viruses were detected concomitantly in HIV-1 RNA from mothers and in HIV-1 DNA from child, suggesting that the cellular reservoir in the child consisted mainly of wild type viruses transmitted by mother. In these cases, detection of resistance mutations in newborns occurred during suboptimal ART pressure of ZDV, used as prophylaxis of MTCT. When ZDV was withdrawn, it led to the re-emergence of wild type viruses in plasma.

Conclusions We showed that a large proportion of HIV-1-infected children presented at birth with plasma resistant virus. In two-thirds of children, the viral stock was early constituted with resistant virus that persisted over time. Resistance study of HIV DNA in infected neonates could be useful to choose the best long-term therapeutical options.