Perinatal Acquisition of Drug-resistant HIV-1 Infection: Mechanisms and Long-term Outcome

Constance Delaugerre; Marie-Laure Chaix; Stephane Blanche; Josiane Warszawski; Dorine Cornet; Catherine Dollfus; Veronique Schneider; Marianne Burgard; Albert Faye; Laurent Mandelbrot; Roland Tubiana; Christine Rouzioux

Disclosures

Retrovirology. 2009;6(2):85 

In This Article

Background

Mother-to-child transmission (MTCT) of HIV-1 mainly occurs during the third trimester of pregnancy or at delivery, in the absence of breastfeeding.[1] Transmission can be prevented by treating the pregnant woman during the third trimester and at delivery, and by giving the child prophylactic treatment during the first weeks of life. The efficacy of this approach was first demonstrated in 1994 with zidovudine,[2] and the transmission rate has gradually fallen in Europe and the United States from 25% to below 2%.[3,4] French guidelines published in 2004 recommend starting combination antiretroviral therapy (HAART) at the end of the second trimester and adding intravenous zidovudine (ZDV) during labor. Infants receive ZDV orally for 6 weeks, alone or combined with other antiretroviral drugs if the risk of transmission is high.[5]

Situations of particular risk of HIV-1 MTCT[4] include unknown maternal HIV-1 serostatus; ineffective maternal ART; maternal primary HIV-1 infection during pregnancy; and suboptimal MTCT prevention.

Infants may be at an increased risk of infection by drug-resistant HIV-1 strains when the mother harbors such viruses or when drug pressure during MTCT prophylaxis is suboptimal.

Vertical transmission of drug-resistant HIV-1 was first reported sporadically,[6–8] but it is now known that 9% to 30% of infected infants exposed to MTCT prophylaxis with ZDV acquire ZDV-resistant viruses.[7,9–12] Masquelier et al. reported finding viruses with ZDV genotypic resistance in 20% of 34 HIV-1-infected infants who were born in France between 1994 and 1996 and were enrolled in the ANRS-EPF French national cohort.[7] In New York State, drug resistance mutations were detected in 12% of perinatally infected infants born in 1998 and 1999[13] and in 19.1% of such infants born in 2001 and 2002.[14]

In France, between 1997 and 2004, the estimated MTCT rate was 1.8% (92 newborns). Here we report the current rate of HIV-1 drug resistance in French neonates born to infected mothers. We also report our investigation as to how these resistant viruses were acquired by the newborns, and the outcome of resistance during infancy.

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