Background:  Viral resistance occurs with high frequency after single-dose nevirapine (NVP) to prevent mother-to-child transmission (PMTCT) and alternative regimens are urgently needed. The objective of this study was to evaluate the safety and resistance profile of a combination of tenofovir disoproxil fumarate (TDF) (300 mg) and emtricitabine (FTC) (200 mg) in HIV-1-infected pregnant women and their newborns.

Methods:  The TEmAA French National Agency for AIDS Research (ANRS) 12109 trial is an open-label phase II trial conducted in Ivory Coast, Cambodia, and South Africa. All HIV-1-infected pregnant women received zidovudine (ZDV, 300 mg twice daily) from the day of enrollment, between the 28^th and 38^th week of gestation, until the beginning of labor, when single-dose NVP (200 mg) and 2 tablets of TDF/FTC were given. One daily tablet of TDF/FTC was administrated during 7 days postpartum. All infants received single-dose NVP syrup on day 1 (2 mg/kg) and ZDV syrup (4 mg/kg twice daily) for 7 days. Mothers and infants were followed until 2 months. Serious adverse events, kinetic of maternal plasma HIV-1 RNA and HIV-1 infection status of the infants at 3 days and 4 weeks of life were assessed using HIV-1 RNA. Genotypic resistance testing and phylogenetic analysis of the reverse transcriptase sequences were performed at week 4 postpartum.

Results:  We enrolled 38 HIV-1-infected pregnant women (19 in Abidjan, 12 in Phnom Penh, and 7 in Soweto), whose median age was 27 years, median CD4 count 450 cells/mm³, and median HIV-1 RNA 4.08 log₁₀ copies/mL. All women received TDF/FTC at a median of 4.9 hours before delivery. Grade 3/4 biological events (anemia, leucopenia) occurred in 9 (24%) women in postpartum. Among 39 live births (1 twin), 9 infants had clinical serious adverse events (23%) Among 39 live births (1 twin), 9 infants had clinically serious adverse events (23%), including 4 who died (meningitis, gastroenteritis, intestinal obstruction, and severe encephalopathy of unknown aetiology) and 2 had transient grade 3 anemia (5%). Maternal HIV-1 RNA decreased by a median of 0.90 log₁₀ copies/mL at 2 days postpartum, and returned to baseline value at 4 weeks postpartum. Plasma HIV-1 RNA was detected in 2 of 39 (5.1%) infants at 3 days and confirmed at 4 weeks of life. No genotypic viral resistance to ZDV, NVP, FTC, or TDF was detected, neither in mothers (15 CRF02-AG, 3 A, 1 CRF06, 11 CRF01-AE, 7 C strains) nor in infants (CRF02-AG and C strains). 

Conclusions:  A TDF/FTC combination for PMTCT appears to be well tolerated in women and exposed newborns:  7 days of postpartum TDF/FTC exposure seem to extend the suppression of viral replication avoiding NVP-resistance mutations.