Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine.
BACKGROUND
Intrapartum single-dose nevirapine plus third trimester maternal and infant zidovudine are essential components of programs to prevent mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings. The persistence of nevirapine in the plasma for 3 weeks postpartum risks selection of resistance mutations to nonnucleoside reverse-transcriptase inhibitors (NNRTIs). We hypothesized that a 1-month zidovudine-didanosine course initiated at the same time as single-dose nevirapine (sdNVP) would prevent the selection of nevirapine-resistance mutations.


METHODS
HIV-infected pregnant women in the PHPT-4 cohort with CD4 cell counts >250 cells/mm3 received antepartum zidovudine from the third trimester until delivery, sdNVP during labor, and a 1-month zidovudine-didanosine course after delivery. These women were matched on the basis of baseline HIV load, CD4 cell count, and duration of antepartum zidovudine to women who received sdNVP in the PHPT-2 trial (control subjects). Consensus sequencing and the more sensitive oligonucleotide ligation assay were performed on samples obtained on postpartum days 7-10, 37-45, and 120 (if the HIV load was >500 copies/mL) to detect K103N/Y181C/G190A mutations.


RESULTS
The 222 PHPT-4 subjects did not differ from matched control subjects in baseline characteristics except for age. The combined group median CD4 cell count was 421 cells/mm3 (interquartile range [IQR], 322-549 cells/mm3), the median HIV load was 3.45 log10 copies/mL (IQR, 2.79-4.00 log10 copies/mL), and the median duration of zidovudine prophylaxis was 10.4 weeks (IQR, 9.1-11.4 weeks). Using consensus sequencing, major NNRTI resistance mutations were detected after delivery in 0% of PHPT-4 subjects and 10.4% of PHPT-2 controls. The oligonucleotide ligation assay detected resistance in 1.8% of PHPT-4 subjects and 18.9% of controls. Major NNRTI resistance mutations were detected by either method in 1.8% of PHPT-4 subjects and 20.7% of controls (P < .001).


CONCLUSIONS
A 1-month postpartum course of zidovudine plus didanosine prevented the selection of the vast majority of NNRTI resistance mutations.
Lallemant
Marc
M
Institut de Recherche pour le Développement U174, Université Paris Descartes, Institut National d'Etudes Démographiques, Institut de Recherche pour le Développment, F-75006, Paris, France. marc@phpt.org
Ngo-Giang-Huong
Nicole
N
Jourdain
Gonzague
G
Traisaithit
Patrinee
P
Cressey
Tim R
TR
Collins
Intira J
IJ
Jarupanich
Tapnarong
T
Sukhumanant
Thammanoon
T
Achalapong
Jullapong
J
Sabsanong
Prapan
P
Chotivanich
Nantasak
N
Winiyakul
Narong
N
Ariyadej
Surabon
S
Kanjanasing
Annop
A
Ratanakosol
Janyaporn
J
Hemvuttiphan
Jittapol
J
Kengsakul
Karun
K
Wannapira
Wiroj
W
Sittipiyasakul
Veerachai
V
Pornkitprasarn
Witaya
W
Liampongsabuddhi
Prateung
P
McIntosh
Kenneth
K
Van Dyke
Russell B
RB
Frenkel
Lisa M
LM
Koetsawang
Suporn
S
Le Coeur
Sophie
S
Kanchana
Siripon
S
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D022521:Ligase Chain Reaction; D020125:Mutation, Missense; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use; D049590:Postpartum Period; D011247:Pregnancy; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D019562:Viral Load; D055815:Young Adult; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D015215:Zidovudine; D019829:Nevirapine; D016049:Didanosine