Background:  Viral resistance occurs with high frequency after single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT) and alternative regimens are urgently needed. The safety and viral response of the tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) combination in HIV-1-infected pregnant women have been shown to be good. It is unknown whether this drug combination can be administered to neonates as well.

Methods:  The TEmAA ANRS 12109 trial is an open-label phase I/II trial conducted in Cambodia, Cote d’Ivoire, and South Africa. In this second part of the trial, 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 weeks of gestation until the beginning of labor, when sdNVP (200 mg) and 2 tablets of TDF/FTC were given. One daily tablet of TDF/FTC was then administered during 7 days postpartum. All infants received sdNVP (2 mg/kg), sdTDF (13 mg/kg), and sdFTC (2 mg/kg) plus 1 week of ZDV (4 mg/kg twice daily). Mothers and infants were followed for 2 months. Serious adverse events, kinetic of maternal plasma HIV-1 RNA and neonatal HIV-1 plasma RNA at 3 and 28 days of life were assessed. Genotypic resistance testing and phylogenetic analysis of the reverse transcriptase sequences were performed at 4 weeks postpartum.

Results:  We enrolled 36 HIV-1-infected pregnant women (15 in Abidjan, 9 in Phnom Penh, and 12 in Soweto):  median age 28 years, median CD4 count 462 cells/mm³, and median HIV-1 RNA 3.6 log₁₀ copies/mL. All women received TDF/FTC at a median of 6 hours before delivery; 2 women received 2 additional tablets of FTC/TDF due to prolonged labor. One grade 3 leukopenia at the onset of labor and one grade 4 neutropenia at day 7 postpartum were reported. Among 30 women with HIV-1 RNA >2.6 log₁₀ copies/mL at enrolment, viral load decreased by a median of 0.5 log₁₀ copies/mL at day 2 postpartum and returned to baseline value at 4 weeks. All 36 live births (median birth weight, 3000 g) received sdTDF and sdFTC. Clinical severe adverse events occurred in 2 infants (5%), including 1 who died (neonatal sepsis). Also reported were 1 transient grade 3 neutropenia and 2 grade 3/4 hyperbilirubinemia; and 1 (2.8%) HIV pediatric in utero infection was diagnosed. Genotypic viral resistance to NVP was detected in 1 mother of 33 (3.0%) (11 CRF02-AG, 2 CRF06, 6 CRF01-AE, 2 B, 11 C, and 1 indeterminate strain), but none to ZDV, FTC, or TDF. 

Conclusions:  Giving the combination of TDF/FTC for PMTCT to women, as well as to their neonates appears to be well tolerated and efficient in both populations.