Background: Detection of antiretroviral (ARV) resistance in HIV-infected individuals is not uncommon and may be particularly problematic in HIV-infected pregnant women as it can lead to infant infection with resistant strains. To better evaluate the effect of drug resistance mutations (DRMs) on HIV mother-to-child transmission (MTCT), we determined the prevalence of DRMs in a subset of mother-infant pairs enrolled in a multi-center trial of infant prophylaxis among women not receiving ARVs during the current pregnancy.
Methods: A case control design of 1:4 (1 transmitter to 4 non-transmitters) was utilized to evaluate ARV resistance as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. Secondary objectives included identification of potential risk factors associated with presence of DRMs. Viroseq HIV-1 Genotyping System was performed on mother-infant specimens to assess for mutations that might result in a substantial reduction in drug susceptibility and clinical outcome, as determined by the Stanford HIV Drug Resistance Database.
Results: One hundred and forty infants were infected. Of these, 123 HIV infected mother-infant pairs and 483 of 560 women who did not transmit HIV had amplifiable HIV nucleic acid enabling ARV resistance testing. A wide variety of DRMs were detected (Figure 1). Sixty (10%) of 606 women had clinically relevant DRMs; 12 (2%) had DRMs against more than 1 ARV class. Among 123 HIV- infected infants, 13 (11%) had clinically relevant DRMs with 3 (2%) harboring DRMs against more than 1 ARV class. Of 13 infants with DRMs, 10 (77%) were infected in-utero. In univariate and multivariate analyses, DRMs in mothers was not associated with increased risk of HIV MTCT (AOR 0.79, 95% CI 0.38-1.5). Log HIV viral load was the only predictor of MTCT (OR 1.4, 95% CI 1.2-1.6). Presence of DRMs in mothers who transmitted was strongly associated with presence of DRMs in infants (p<0.001).
Conclusion: In infected pregnant women without ARV exposure during their current gestation, presence of pre-existing DRMs with a wide diversity was noted. DRMs do not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed they are likely to transmit resistant mutations even without selective ARV pressure, thus complicating treatment options.
B. Ank, None
H. Watts, None
M. Camarca, None
E. Joao, None
J. H. Pilotto, None
V. Veloso, None
Y. Bryson, None
K. Nielsen-Saines, None