Safety of nevirapine in pregnancy

Department of Genitourinary Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK.
HIV Medicine (Impact Factor: 3.45). 02/2007; 8(1):64-9. DOI: 10.1111/j.1468-1293.2007.00433.x
Source: PubMed

ABSTRACT Nevirapine has been widely used in pregnancy for its efficacy, low pill burden, bioavailability and rapid transplacental transfer. Concern about nevirapine toxicity during pregnancy has emerged over recent years.
The aims of the study were to document the frequency of cutaneous and hepatic toxicity secondary to nevirapine use during pregnancy and to compare rates in women starting nevirapine during the current pregnancy with those in women who had commenced nevirapine prior to the current pregnancy.
This was a retrospective, comparative, five-centre study carried out in London, UK, in 1997-2003.
All HIV-1-infected women who received nevirapine as part of combination antiretroviral therapy (ART) during pregnancy were included in the study. Data on demographics, HIV infection risk, Centers for Disease Control and Prevention (CDC) status, surrogate markers at initiation of therapy, other medications hepatitis B and C virus coinfection and clinical data relating to potential toxicity were collated and analysed.
Fifteen of 235 eligible women (6.4%) developed rash and eight (3.4%) developed hepatotoxicity, including four with coexistent rash, giving a combined incidence of 19 potential cases of nevirapine toxicity during pregnancy (8.1%). Alternative causes of rash/hepatotoxicity were suspected in seven cases and only 10 mothers (5.8%) discontinued nevirapine. Of the 170 women who commenced nevirapine during this pregnancy, 13 (7.6%) developed rash and eight (4.7%) hepatotoxicity, a combined incidence of 10%. Only two of 65 women with nevirapine exposure prior to this pregnancy developed rash (3.1%).
Nevirapine-containing ART was well tolerated in this cohort of pregnant women. Although pregnancy did not appear to increase the risk of nevirapine-associated toxicity compared to published adult data, CD(4) count may be less predictive of toxicity in pregnancy.

Download full-text


Available from: Jane Anderson, Nov 02, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Synthesis of chalcogen (S and Se) derivatives of 4-chloro- and 4-methoxy-N,N-diisopropylpyridine-2-carboxamide (1a and 1b respectively) has been reported. 1a and 1b were lithiated with 2 equiv. of n-BuLi or LDA at −78 °C. Addition of elemental sulfur or selenium to the carbanion led to the formation of corresponding thiolate or selenolate anions respectively. The selenolate anions were aerial oxidized to afford the corresponding diselenides. The thiolate/selenolate anions were quenched with a variety of electrophiles to give unsymmetrical thio/selenoalkanes in moderate to good yields. Reductive cleavage of Se–Se bond has also been studied. The synthesized compounds were characterized by elemental analysis, NMR (1H, 13C and 77Se), FT-IR and mass spectral techniques. Crystal structures of two compounds, 6b and 7a, were determined by single crystal X-ray crystallography. Their crystal structure exhibits 1,4-type S⋯OCH3 and Se⋯Cl intramolecular secondary interactions respectively. The relative thermal stability of 3a, 3b and 4a has also been established by thermogravimetric analysis.
    Journal of Organometallic Chemistry 06/2011; 696(11):2406-2413. DOI:10.1016/j.jorganchem.2011.03.009 · 2.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This retrospective cohort study evaluated the risk of hepatotoxicity in HIV-1 positive pregnant and non-pregnant women starting combined ART. Data were used from the ATHENA observational cohort. The study population consisted of HIV-1 infected, therapy naïve, pregnant and non-pregnant women, followed between January 1997 and February 2008. Demographic, treatment and pregnancy related data were collected. Risk of hepatotoxicity was determined using univariate and multivariate logistic regression. Analyses were adjusted for age, region of origin, baseline HIV-RNA levels and CD4 cell counts, cART regimen and hepatitis B and C coinfection. ALT and AST values of more than 5 times ULN were considered as hepatotoxicity. Four-hundred and twenty-five pregnant and 1121 non-pregnant women were included. Independent risk factors of hepatotoxicity in all women were the presence of detectable HCV RNA (OR 5.48, 95% CI 2.25-13.38, p<0.001) and NVP use (OR 2.63, 95% CI 1.54-4.55, p<0.001). Stratified for pregnancy, the adjusted risk of hepatotoxicity was significantly associated with HCV coinfection only during pregnancy (OR 23.53, 95% CI 4.69-118.01, p<0.001). NVP use is related to hepatotoxicity in pregnant (OR 5.26, 95% CI 1.61-16.67, p<0.005) as well as in non-pregnant women (OR 2.13, 95% CI 1.11-4.00, p=0.02). HCV coinfection and NVP use are associated with a higher risk of cART induced hepatotoxicity in pregnant women.
    The Journal of infection 12/2011; 64(4):409-16. DOI:10.1016/j.jinf.2011.12.012 · 4.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.
    HIV Medicine 09/2012; 13 Suppl 2:87-157. DOI:10.1111/j.1468-1293.2012.01030_2.x · 3.45 Impact Factor