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Background: An increasing number of HIV-infected women become pregnant while receiving efavirenz (EFV). We compared the pregnancy outcomes of women exposed to EFV and to nevirapine (NVP) during the first trimester., Methods: A retrospective study in 4 HIV care centers participating to clinical trials and international cohort collaboration. All HIV-infected pregnant women who conceived on EFV-based or NVP-based antiretroviral therapy (ART) between 2003 and 2009 were included. Pregnancy outcomes were as follows: abortion (voluntary termination), miscarriage [unwanted termination <20 weeks of amenorrhea (WA)], stillborn (death ≥ 20 WA), preterm delivery (live-birth <37 WA), and low birth weight (LBW) (<2500 grams)., Results: Overall, 344 HIV-infected pregnant women conceived on ART (213 on EFV and 131 on NVP). Median age was 29 years, and median CD4 count 217 cells per microliter at ART initiation. The overall proportion was 11.7% for abortion, 5.2% for miscarriage, 6.7% for stillborn, 10.8% for preterm delivery, and 20.2% for LBW. There was no difference between EFV and NVP exposure, except for abortion (14.3% vs 7.3%; P = 0.05). No external and visible congenital malformation was observed neither in women exposed to EFV nor in women exposed to NVP., Conclusions: Among women exposed to EFV, no significant increased risk of unfavorable pregnancy outcome was reported except for abortion.

Background: In resource-limited settings where nevirapine-containing regimen is the preferred regimen in women, data on severe adverse events (SAEs) according to CD4 cell count are limited. We estimated the incidence of SAEs according to CD4 cell count and identify their risk factors in nevirapine-treated women., Methods: All HIV-infected women who initiated nevirapine-containing regimen in the MTCT-Plus operational program in Abidjan, Côte d'Ivoire, were eligible for this study. Laboratory and clinical (rash) SAEs were classified as grade 3 and 4. Cox models were used to identify factors associated with the occurrence of SAEs., Results: From August 2003 to October 2006, 290 women initiated a nevirapine-containing regimen at a median CD4 cell count of 186 cells/mm3 (IQR 124-266). During a median follow-up on treatment of 25 months, the incidence of all SAEs was 19.5/100 patient-years. The 24-month probability of occurrence of hepatotoxicity or rash was not different between women with a CD4 cell count >250 cells/mm3 and women with a CD4 cell count 250 cells/mm3 at treatment initiation nor initiation NVP-based regimen initiated during pregnancy were associated with the occurrence of SAEs., Conclusion: CD4 cell count >250 cells/mm3 was not associated with a higher risk of severe hepatotoxicity and/or rash, as well as initiation of ART during pregnancy. Pharmacovogilance data as well as meta-analysis on women receiving NVP in these settings are needed for better information about NVP toxicity.

Nonnucleoside reverse transcriptase inhibitor resistance following the use of single-dose nevirapine (sdNVP) for the prevention of mother-to-child transmission (PMTCT) remains a concern. In the ANRS-1201/1202 Ditrame study, conducted in Abidjan, Côte d'Ivoire, a short-course regimen of zidovudine was associated with sdNVP for PMTCT. In this study, we estimate the frequency of NVP resistance and its relationship with NVP concentration in mothers. Genotypic resistance analysis was performed on mothers' plasma samples at week 4 postpartum (PP) and on human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMC) when an NVP resistance mutation was detected. The same tests were performed for the infected children at week 4, month 3, and month 12. Mothers' NVP plasma concentrations were measured at 48 h PP. Twenty-one (33%) of the 63 women selected had NVP-resistant (NVP-R) virus at week 4 PP. The median plasma NVP concentration was 598 ng/ml for the mothers without NVP-R virus compared to 851 ng/ml for the mothers harboring NVP-R virus (P = 0.014). NVP-R mutations were detected in the HIV DNA of 15/20 women. Plasma NVP-R mutations were detectable in 6 of 26 infected children at week 4. All 6 children had detectable NVP-R mutations in HIV DNA of PBMC. Blood samples taken at month 3 (1 child) and month 12 (1 child) revealed the persistence of NVP-R mutations in plasma and cells. Emergence of NVP-R virus in mothers is strongly correlated with a high level of plasma NVP concentration, owing to a prolonged postpartum period of viral replication under NVP selective pressure. The follow-up of the cohort demonstrates the prolonged archive of resistant virus.