Safety of nevirapine in pregnancy

Department of Genitourinary Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK.
HIV Medicine (Impact Factor: 3.99). 02/2007; 8(1):64-9. DOI: 10.1111/j.1468-1293.2007.00433.x
Source: PubMed


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.

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Available from: Jane Anderson, Nov 02, 2014
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    • "Author Year ART-naive (N) Region Period Study design TTT Liver (n) Skin (n) Deaths (n) Aaron 30 2010 79 USA 1999 -2005 Retrospective 42 2 6 N/R Coffie 31 2010 125 Cote d'Ivoire 2003 -2006 Prospective 58 5 3 6 Gonzales 32 2004 170 USA 1997 -2003 Retrospective N/R 6 5 0 Hitti 27 2004 17 USA 2003 -2004 Randomised 63 3 1 1 Jamisse 33 2007 146 Mozambique 2004 -2005 Prospective 36 4 4 0 Joy 34 2005 22 USA 2001 -2005 Retrospective 42 3 0 0 Kilewo 35 2009 429 Tanzania 2004 -2006 Prospective N/R 2 7 0 Kondo 4 2007 133 Brazil 2003 -2006 Retrospective 27 2 21 0 Lyons 36 2006 85 Ireland 2000 -2003 Retrospective 32 8 1 2 Marazzi 5 2006 703 Mozambique 2002 -2004 Retrospective 74 46 25 5 Natarajan 28 2007 153 UK 1997 -2003 Retrospective 42 5 6 0 Peters 29 2011 310 Kenya 2003 -2006 Prospective 68 12 16 0 Phanuphak 37 2007 244 Thailand N/R Prospective 42 15 9 0 Van Schalkwyk 38 2008 47 Canada 2001 -2005 Prospective 33 3 1 0 Total 2 663 116 105 14 "
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    ABSTRACT: Background. The package insert for nevirapine (NVP) cautions use in HIV-infected women (including pregnant women) with CD4 counts ≥250 cells/µl. However, recent studies showed that the CD4 count of pregnant women receiving antiretroviral therapy (ART) was not predictive of NVP toxicity. Objectives. To determine whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts experience greater toxicity compared with pregnant women at lower CD4 counts. Methods. We reviewed studies comparing serious adverse NVP-related events among ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts. Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals and conference proceedings prior to December 2011. Authors were contacted for additional data. Data were independently extracted and entered into Review Manager. Results. Fourteen studies (2 663 participants) were included for analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with CD4 <250 cells/µl was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When analysis was restricted to prospective studies only (7 studies, 1 318 participants), the results were consistent for overall NVP toxicity (OR 0.43; 95% CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10). Conclusion. Initiating NVP-based ART during pregnancy at CD4 ≥250 cells/µl increases toxicity risk and should be avoided, necessitating urgent revision of current guidelines supporting this practice.
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