Nevirapine-Associated Hepatotoxicity and Rash among HIV-Infected Pregnant Women in Kenya

Peters, Philip J.; Polle, Nicholas; Zeh, Clement; Masaba, Rose; Borkowf, Craig B.; Oyaro, Boaz; Omolo, Paul; Ogindo, Paul; Ndivo, Richard; Angira, Frank; Lando, Richard; Fowler, Mary Glenn; Weidle, Paul J.; Thomas, Timothy K.

doi:10.1177/1545109711423445

Cited by 10 publications

(8 citation statements)

References 26 publications

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“…Two studies with CD4 cut-offs of 500 29 Fourteen studies were reviewed, including a total of 2 663 participants (Table 2). 4,5,[27][28][29][30][31][32][33][34][35][36][37][38] One study was funded by the NVP manufacturer Boehringer Ingelheim. 30 The studies, mostly undertaken between 2001 and 2006, were predominantly observational with participant numbers ranging from 17 to 703.…”

Section: Resultsmentioning

confidence: 99%

“…Participants with hepatitis B or C infection were excluded from 2 studies, 4,27 whereas 7 studies reported the prevalence of hepatitis co-infection. [28][29][30]34,[36][37][38] NVP was initially commenced at 200 mg daily for 14 days in all women. The CD4 cut-off was 250 cells/µl for toxicity analyses in all studies, except for one (CD4 cut-off of 200 cells/ µl).…”

Section: Resultsmentioning

confidence: 99%

“…11 Combining hepatotoxicity data for NFV and NVP may potentially dilute the association between NVP and hepatotoxicity at higher CD4 counts. As an example, in the study by Peters et al, 29 only 1 of 208 women with CD4 ≥250 cells/µl initiated NVP during the second enrolment period. The remaining 207 women started NFV.…”

Section: Discussionmentioning

confidence: 99%

“…24,29,30 Nelfinavir use is rarely associated with hepatotoxicity. 11 Combining hepatotoxicity data for NFV and NVP may potentially dilute the association between NVP and hepatotoxicity at higher CD4 counts.…”

Section: Discussionmentioning

confidence: 99%

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Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: A systematic review and meta-analysis

Bera

Mia

2012

S Afr Med J

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United States (US) Food and Drug Administration (FDA) issued a public health advisory recommending against initiating nevirapine (NVP) in HIV-infected women (including pregnant women) with CD4 counts >250 cells/µl. 1 The NVP package insert was revised accordingly to warn about risks, with further revision in November 2011 to comply with FDA recommendations on product labelling safety. 2The initial warning followed a meta-analysis of hepatotoxicity in over 600 women, stratified by CD4 count (risk ratio 9.8 with a CD4 count ≥250 cells/µl).3 However, results from several subsequent studies with larger datasets demonstrated no association between CD4 count and NVP toxicity. [4][5][6] Current World Health Organization (WHO) guidelines recommend NVP as part of first-line antiretroviral therapy (ART) for pregnant women with CD4 ≤350 cells/µl, 7 based on their own analysis of 836 pregnant women, which showed no increased hepatotoxicity risk at CD4 ≥250 cells/µl (relative risk 1.04; 95% confidence interval (CI) 0.22 -4.93). 9 In contrast, the 2011 perinatal guidelines from the US Department of Health and Human Services recommend a protease inhibitor as part of the ART regimen for pregnant women with a CD4 count ≥250 cells/µl, while cautioning against starting NVP above this count. 10 The British HIV Association 2012 draft guidelines recommend either efavirenz (EFV) or NVP (with a CD4 count <250 cells/µl) or a boosted protease inhibitor as the third drug for pregnant women requiring ART for their own health. 11 The recommendation of EFV is a departure from previous guidelines discouraging its use in pregnancy. Furthermore, women who conceived on EFV-based ART need not switch to another drug in the first trimester, following analysis of recent data showing no increased risk of birth defects after first-trimester EFV exposure. 11Reports of NVP-related maternal deaths have surfaced in South Africa, generating renewed concerns about the drug's safety, notably among ART-naive pregnant women. The Eastern Cape Province recently amended its PMTCT guidelines following an analysis of 45 HIV-related maternal deaths, 6 due to liver failure and StevensJohnson Syndrome (SJS). The use of NVP in pregnancy since then has been limited to a single dose at delivery (M Shweni, personal communication).To address the uncertainty about the safety of initiating NVPbased ART in pregnancy, we aimed to determine whether ART-naive pregnant women initiating NVP at higher CD4 counts experience greater toxicity. MethodsThe Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) guidelines were followed.12 All studies except case reports were evaluated for inclusion without consideration of their results. ART-naive pregnant women initiating NVP-based ART during the index pregnancy for maternal health or infant prophylaxis were included. For studies that included both ART-naive and -experienced pregnant women, only the data of ART-naive participants were extracted. ART-experienced pregnant women were excluded, including those naive to N...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: A systematic review and meta-analysis

Bera

Mia

2012

S Afr Med J

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“…Las reacciones tóxi-cas pueden aparecer entre los 10 y los 280 días de iniciado el tratamiento (23)(24)(25)(26). La hepatotoxicidad se ha presentado en pacientes con edad entre los 18 y 45 años (21, 24-27), con elevación de las transaminasas y rash (23,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

Section: Valoración De La Aparición De Hepatotoxicidadunclassified

Medicamentos causantes de hepatotoxicidad en el embarazo: revisión estructurada

Amariles

2017

Rev. Colomb. Gastroenterol.

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Objetivo: identificar los medicamentos y determinar las principales características asociadas con hepatotoxicidad por medicamentos en el embarazo.Método: revisión estructurada en PubMed/Medline, EMBASE y Web of Science utilizando los términos: Drug induced liver injury OR Hepatotoxicity AND Pregnancy. La búsqueda incluyó artículos en inglés, español, humanos, entre 2005 y 2015, con información sobre hepatotoxicidad por medicamentos en el embarazo. Fueron excluidos los artículos sin relación con embarazo o hepatotoxicidad, asociados con otras causas de enfermedad hepática o con hepatotoxicidad por otras sustancias. La información del medicamento y las características de los pacientes fueron registradas en una tabla. La probabilidad de la aparición de hepatotoxicidad fue valorada y agrupada en tres categorías: definida, probable y posible; para algunos medicamentos fue determinada por el método RUCAM.Resultados: fueron identificados 488 artículos, de los cuales 46 fueron seleccionados. Fueron identificados también 12 medicamentos (acetaminofeno, alfametildopa, labetalol, metotrexato, saquinavir, nevirapina, propiltiouracilo, metimazol, carbimazol, nitrofurantoína, ácido acetilsalicílico y piperidolato) con probabilidad de causar hepatotoxicidad en el embarazo. Algunas características asociadas con los fármacos fueron: tiempo de aparición de las reacciones, semanas de embarazo (3-36), factores de riesgo (edad y enfermedades crónicas), manifestaciones clínicas (elevación de transaminasas, prurito, ictericia) y desenlaces (trasplante de hígado, muertes materna y fetal).Conclusión: los medicamentos acetaminofeno, alfametildopa, labetalol, metotrexato, saquinavir, nevirapina, propiltiouracilo, metimazol, carbimazol, nitrofurantoína, ácido acetilsalicílico y piperidolato podrían causar hepatotoxicidad en pacientes embarazadas. Además de la dosis y del tiempo de exposición al fármaco, la edad y el tiempo de gestación podrían influir en la presentación y gravedad de la hepatotoxicidad.

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Adverse events associated with nevirapine use in pregnancy

Ford

Calmy

Andrieux-Meyer

et al. 2013

Aids

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Nevirapine-Associated Hepatotoxicity and Rash among HIV-Infected Pregnant Women in Kenya

Abstract: Nevirapine use but not CD4 count ≥250 cells/mm(3) was associated with hepatotoxicity.

Cited by 10 publications

References 26 publications

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: A systematic review and meta-analysis

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: A systematic review and meta-analysis

Medicamentos causantes de hepatotoxicidad en el embarazo: revisión estructurada

Adverse events associated with nevirapine use in pregnancy

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