Journal
CLINICAL INFECTIOUS DISEASES
Volume 50, Issue 6, Pages 898-908Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/650745
Keywords
-
Categories
Funding
- Global Fund
- Tuberculosis and Malaria Thailand [PR-A-N-008]
- National Institutes of Health [5 R01 HD 33326, PHPT-2, R01 AI058723, UO1 AI068632]
- Agence Nationale de Recherches sur le Sida [PHPT-2, ANRS 12-32]
- Ministry of Public Health, Thailand
- Institut de Recherche pour le Developpement, France
- Institut National d'Etudes Demographiques, France
- Department of Technical and Economic Cooperation, Thailand
- Boehringer Ingelheim and GlaxoSmithKline
- AIDS Research and Reference Reagent Program
- Division of AIDS
- NIAID
Ask authors/readers for more resources
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/mm(3) 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/mm(3) (interquartile range [IQR], 322-549 cells/mm3), the median HIV load was 3.45 log(10) copies/mL (IQR, 2.79-4.00 log(10) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available