Tolerance and viral resistance after single-dose nevirapine with tenofovir and emtricitabine to prevent vertical transmission of HIV-1.
OBJECTIVE
Viral resistance occurs with high frequency after single-dose nevirapine. We aimed to evaluate the safety and resistance profiles of a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in HIV-1-infected pregnant women and their newborns.


METHODS
An open-label phase I/II trial in Côte d'Ivoire, Cambodia and South Africa.


METHODS
Women received antenatal zidovudine, intrapartum single-dose nevirapine and two tablets of TDF/FTC and one daily tablet of TDF/FTC during the 7 days postpartum. Their infants received single-dose nevirapine and zidovudine for 1 week. Serious adverse events (SAEs), kinetic of maternal plasma HIV-1 RNA viral load, genotypic resistance at 28 days postpartum and paediatric HIV-1 infection at 3, 28 and 45 days of life were assessed.


RESULTS
Thirty-eight HIV-1-infected pregnant women were enrolled (19 in Abidjan, 12 in Phnom Penh and seven in Soweto) with a median CD4 cell count of 450 cells/microl and median viral load of 4.08 log10 copies/ml. Women received TDF/FTC 4.9 h in median before delivery. Biological SAEs occurred in nine women. Among 39 live births, nine infants had clinical SAEs, including four deaths, and two developed severe anaemia. These SAEs were not likely to be related to TDF/FTC. Maternal viral load decreased by a median of 0.90 log10 copies/ml at 2 days postpartum and returned to baseline value at 28 days. No intrapartum HIV transmission was reported. No genotypic resistance mutation to zidovudine, nevirapine, FTC or TDF was detected.


CONCLUSIONS
The TDF/FTC combination was well tolerated in delivering women and exposed newborns. Nevirapine viral resistance appears to have been avoided by the intrapartum and 7-day postpartum TDF/FTC regimen.
Arrivé
Elise
E
Chaix
Marie-Laure
ML
Nerrienet
Eric
E
Blanche
Stéphane
S
Rouzioux
Christine
C
Coffie
Patrick A
PA
Kruy Leang
Sim
S
McIntyre
James
J
Avit
Divine
D
Srey
Viseth Horm
VH
Gray
Glenda
G
N'Dri-Yoman
Thérèse
T
Diallo
Alpha
A
Ekouévi
Didier K
DK
Dabis
François
F
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002160:Cambodia; D007560:Cote d'Ivoire; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019829:Nevirapine / Q000008:administration & dosage*; D063065:Organophosphonates / Q000008:administration & dosage*; D011247:Pregnancy; D012367:RNA, Viral / Q000235:genetics; D013019:South Africa; D000068698:Tenofovir; D019562:Viral Load
D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D019829:Nevirapine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine