JAIDS Journal of Acquired Immune Deficiency Syndromes:
Serious Adverse Cutaneous and Hepatic Toxicities Associated With Nevirapine Use by Non–HIV-Infected Individuals
Patel, Shilpa M. MD†; Johnson, Stuart MD∥; Belknap, Steven M. MD†; Chan, Juliana Pharm D‡; Sha, Beverly E. MD§; Bennett, Charles MD, PhD*†
From the *Veterans Affairs Chicago Healthcare System/Lakeside Division, Chicago, IL; †Divisions of Infectious Diseases, and Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Institute for Health Services Research and Policy Studies of Northwestern University, Chicago, IL; ‡Department of Pharmacy Practice, College of Pharmacy, and Department of Medicine, Sections of Digestive and Liver and Infectious Diseases, University of Illinois at Chicago, Chicago, IL; and §Department of Medicine, Section of Infectious Diseases, Rush Medical College, Chicago, IL, and ∥Hines Veterans Affairs Hospital and the Stritch School of Medicine, Loyola University, Maywood, IL.
Received for publication July 4, 2003; accepted October 14, 2003.
Reprints: Charles Bennett, Veterans Affairs Chicago Healthcare System/Lakeside Division, 400 East Ontario Street, Chicago, IL 60611 (e-mail: email@example.com).
Background: Nevirapine is a nonnucleoside reverse transcriptase antiretroviral agent. Among HIV-infected individuals, rare instances (<1%) of serious cutaneous and hepatic toxicity have been reported. Because of its favorable pharmacokinetic profile, non–HIV-infected individuals have received nevirapine-containing postexposure prophylaxis (PEP).
Objective: To describe the clinical features of cutaneous and hepatic toxicity that occurred when nevirapine was administered to non–HIV-infected individuals.
Methods: Reports of nevirapine-associated cutaneous or hepatic toxicity occurring among non–HIV-infected individuals were obtained from the US Food and Drug Administration's adverse event reporting system, the pharmaceutic manufacturer, occupational health programs in Chicago, physicians, and case reports. The Eastern Cooperative Oncology Group (ECOG) scoring system was used to grade toxicity.
Results: Twelve non–HIV-infected individuals developed severe cutaneous toxicity, including 3 with Stevens-Johnson syndrome, after 7 to 12 days of nevirapine-containing PEP regimens. Thirty non–HIV-infected individuals developed hepatotoxicity after 8 to 35 days of single-agent nevirapine (n = 8) or a nevirapine-containing PEP regimen (n = 22). Findings included ECOG grade 3 or 4 hepatotoxicity (n = 14), fevers (n = 11), skin rashes (n = 8), eosinophilia (n = 6), and fulminant hepatic necrosis requiring an orthotopic liver transplant (n = 1). Rates of severe hepatotoxicity (grade 3 or 4) in non–HIV-infected individuals ranged from 10% (4/41) to 62% (5/8). Liver biopsy material from 2 individuals was consistent with a hypersensitivity syndrome.
Conclusions: Serious hepatic and cutaneous toxicities can occur in non–HIV-infected individuals who receive short-term nevirapine therapy. The rate of severe hepatotoxicity appears to be greater in non–HIV-infected individuals than in HIV-infected persons and may be associated with higher CD4 counts. The use of PEP regimens containing nevirapine should be discouraged.
Nevirapine is a nonnucleoside reverse transcriptase inhibitor proven effective as a part of highly active antiretroviral therapies for HIV infection and for prevention of placental transfer of HIV. 1 Nevirapine does not require phosphorylation to an active metabolite, 2 and it has a high oral bioavailability with a long half-life. 3 HIV viral load undetectability occurs shortly after the initiation of nevirapine-containing HIV regimens in HIV-1–positive patients. 4 Major adverse reactions, including skin rashes and hepatotoxicity, occur in <1% of HIV-infected individuals. 5 Review of 4 randomized clinical trials, which included 2700 subjects on either nevirapine or placebo, identified a 3.4% 1-year rate of hepatitis or related hepatic events. Higher rates of hepatic toxicity were observed among persons who had higher CD4+ levels. 6
The pharmacokinetic properties of nevirapine are theoretically advantageous in the setting of postexposure prophylaxis (PEP). Enthusiasm for this use diminished when reports appeared of non–HIV-infected health care workers (HCWs) and sexual contacts who developed hepatotoxicity following use of a nevirapine-containing PEP regimen. 7–11 As with all new agents, however, a comprehensive safety assessment requires diligent postmarketing surveillance. Safety considerations are especially important when pharmaceutic agents are used “off label” in the clinical setting. Based on reports of severe hepatotoxicity in PEP patients and the absence of supportive clinical trials in this population, the Centers for Disease Control and Prevention (CDC) cautioned against the use of nevirapine for PEP. 9 Herein, we describe the clinical and laboratory findings of cutaneous or hepatic toxicity that occurred when non–HIV-infected individuals received short-term nevirapine therapy.
Individual case histories of nevirapine-associated cutaneous or hepatic toxicity occurring among non–HIV-infected individuals were obtained from MedWatch, the US Food and Drug Administration's (FDA) passive reporting system (n = 19), 7 queries of HIV specialists (n = 6), the pharmaceutic supplier of nevirapine (n = 8), and published reports (n = 9). 10–16 Severe hepatotoxicity was characterized as Eastern Cooperative Oncology Group (ECOG) grade 3 or 4 (>5 times normal elevations in hepatic transaminases: alanine aminotransferase [ALT] or aspartate aminotransferase [AST], alkaline phosphatase [Alk Phos], and/or >1.5 times normal elevation in total bilirubin). Severe cutaneous toxicity was characterized as ECOG grade 3 or 4 (generalized symptomatic macular, papular, or vesicular eruption; exfoliative dermatitis; or ulcerating dermatitis). A serious adverse event was operationally described as an event that resulted in hospitalization, resulted in loss of time from work, was permanently or severely disabling, resulted in death or liver transplantation, and/or required emergency medical attention. Liver biopsies were reviewed by 2 experienced hepatologists for 2 non–HIV-infected HCWs who developed severe hepatic toxicities. The rates of nevirapine-associated cutaneous and hepatic toxicities were obtained from 2 sources: an unpublished phase 1 trial, where 41 non–HIV-infected volunteers received nevirapine (Maureen Oakes, Pharm D, Boehringer-Ingelheim, personal communication, December 13, 2000), and a survey of 5 occupational health programs in Chicago that prescribed nevirapine-containing PEP regimens after occupational exposures to HIV-infected blood or body fluids. 16
Nevirapine-associated ECOG grade 3 or 4 cutaneous toxicity without hepatic involvement was noted in 12 non–HIV-infected individuals (7 HCWs, 1 child, and 4 other adults) at a median of 9 days after initiation of PEP (range: 7–12 days) (Table 1). Exposure occurred via a needlestick (7 cases), fluid splash (1 case), and unknown route (4 cases). PEP was taken for a median duration of 13 days (range: 6–30 days). The recommended lead-in nevirapine dose of 200 mg once daily for 2 weeks prior to the 200-mg twice-daily schedule was used for 75% of the cases. Extracutaneous symptoms included fever (5 cases) and rhabdomyolysis (1 case). Three patients developed Stevens-Johnson syndrome. Four individuals were hospitalized for cutaneous toxicity events. After discontinuation of nevirapine, all the affected individuals rapidly improved.
Thirty non–HIV-infected individuals (12 HCWs, 3 sexual contacts of HIV-infected individuals, 8 clinical trial participants, and 7 other individuals) developed hepatotoxicity after a median of 20.5 days (range: 8–35 days) of nevirapine treatment (Table 2). Findings included grade 3 or 4 hepatotoxicity (n = 14), fevers (n = 11), skin rashes (n = 8), eosinophilia (n = 6), and fulminant hepatic necrosis requiring an orthotopic liver transplant (n = 1). No other causes for rashes or severe hepatotoxicity were identified. After discontinuation of nevirapine, all but 2 of these non–HIV-infected individuals improved within a median of 21.5 days (range: 14–60 days). Hepatotoxicity persisted in 1 HCW for 2 months after discontinuation of the nevirapine-containing PEP regimen; at that time, a course of corticosteroids was initiated, and 2 months later, the hepatotoxicity resolved. One HCW developed fulminant hepatic necrosis and coma and received a liver transplant 14 days after discontinuation of the nevirapine-containing PEP regimen. None of the non–HIV-infected individuals developed a positive serologic test for HIV or hepatitis C infection. Liver biopsy material showed extensive hemorrhagic central zonal necrosis, portal tract eosinophils, and lymphocytes in 1 non–HIV-infected HCW who developed fulminant hepatic necrosis (patient 15, see Table 2) and central zonal cholestasis with bile canalicular plugs, mild portal tract eosinophils, and no hepatocyte necrosis in 1 non–HIV-infected HCW who developed gradual but progressive jaundice that improved with 2 months of corticosteroids and discontinuation of nevirapine (patient 17, see Table 2).
Some information was available that allowed for rate estimation of severe nevirapine-associated hepatic or cutaneous toxicity in the setting of non–HIV-infected individuals. During a phase 1 trial with 41 non–HIV-infected volunteers who received between 6 and 15 days of nevirapine, 4 individuals developed nevirapine-associated grade 1 or 2 hepatotoxicity (10%) and 4 developed grade 3 or 4 hepatotoxicity (10%) (Maureen Oakes, Pharm D, Boehringer-Ingelheim, personal communication, December 13, 2000). The hepatic toxicity reversed rapidly with drug discontinuation. Among 8 HCWs in Chicago who received nevirapine-containing PEP regimens, 5 (62%) developed grade 3 or 4 hepatotoxicity.
Nevirapine is a potent nonnucleoside inhibitor of HIV-1 reverse transcriptase. When used in combination with nucleoside analogue reverse transcriptase inhibitors, it produces significant and sustained reductions in HIV viremia. In this study, we have described the clinical and laboratory findings of cutaneous or hepatic toxicity that occurred in 42 non–HIV-infected individuals who received nevirapine-containing antiretroviral therapies. Cutaneous toxicity and hepatic toxicity were not always linked, and severe life-threatening reactions such as Stevens-Johnson syndrome and fulminant hepatic failure were seen in different individuals. In interpreting our findings, several factors should be considered.
First, attribution of the cause of hepatotoxicity can be difficult. 17 Stavudine, a nonnucleoside HIV-1 reverse transcriptase inhibitor used by the majority of the patients with PEP in our series, is the most commonly reported agent causing mitochondrial toxicity and hepatitis, but this toxicity has also been seen with lamivudine, zidovudine, and didanosine. 18 The manifestations of mitochondrial toxicity may include fulminant hepatitis without fever and eosinophilia. Lactic acid levels that are usually markedly elevated with mitochondrial toxicity were only mildly elevated when measured for several cases in our study. Also, the histologic hallmark of mitochondrial toxicity, microvesicular hepatic steatosis, was not identified in liver biopsy materials obtained from 2 individuals in this study. In some cases, hepatic toxicity can result in an immune-mediated liver injury, in which neoantigens are generated as a consequence of a reaction between liver proteins and reactive drug metabolites. 19
Second, our study raises concern that individuals without immunodeficiency are at greater risk for the development of nevirapine-associated hepatotoxicity, which may occur in conjunction with rash and eosinophilia. An unpublished phase 1 clinical trial and a survey of occupational health programs identified high rates of nevirapine-associated toxicity among non–HIV-infected individuals. 16 A study from London identified a 20% rate of grade 3 or 4 hepatotoxicity among 49 non–HIV-infected HCWs or sexual contacts who received nevirapine-containing PEP regimens. 11 Hypersensitivity reactions consisting of rash, peripheral eosinophilia, constitutional symptoms, and hepatic dysfunction have been reported among HIV-infected individuals, typically within the first 2 months of treatment. 20–22 If the hypersensitivity reactions were mediated by CD4 lymphocytes, this could account for the occurrence of hepatotoxicity among non–HIV-infected individuals.
The primary treatment of hypersensitivity syndromes is removal of the causative agent. Although corticosteroid administration is controversial, this therapy has been used when symptoms are severe. 22,23 There are case reports where corticosteroids have been useful for the treatment of the nevirapine-associated hepatic toxicity that occurs in conjunction with hypersensitivity reactions. 24–29 Of the non–HIV-infected HCWs with severe hepatic toxicity after use of a nevirapine-containing PEP regimen described in this report, 2 did not improve until high-dose prednisone was administered. In contrast, randomized clinical trials have shown that corticosteroids do not prevent the development of nevirapine-associated cutaneous toxicity. 30,31
It is important to note that our findings do not apply to single-dose nevirapine use for the prevention of perinatal HIV transmission. To date, no serious toxicity has been reported among mother–infant pairs who receive single-dose nevirapine prophylaxis regimens, and nevirapine has been proven to be one of the most effective agents in this setting.
Third, identifying rare but serious adverse drug reactions infrequently occurs during clinical testing. Three methods exist for identifying adverse drug reactions in the postmarket approval period. 27,28 The first is the MedWatch program, in which health care professionals are encouraged on a voluntary basis to submit details of serious events that may have been caused by any FDA-regulated product. Although reports can be transmitted by telephone, telefax, mail, or the Internet, only 1% to 10% of serious events that might represent an adverse drug reaction are reported. 27 Less than half of the cases in this study were included in MedWatch reports. The second method, postmarketing cohort studies, is unlikely to provide information about nevirapine toxicity in non–HIV-infected individuals, because no clinical studies in the setting of PEP have been initiated. The third method, conducting active surveillance, is often the best method for identifying toxicities of drugs. Active surveillance in this study included obtaining case histories from physicians who directed employee health programs in our local area. Previously, we used similar methods to identify cases of another rare but potentially fatal adverse drug reaction, ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura. 29,32
In conclusion, nevirapine is commonly used for the treatment of HIV-infected individuals and for prevention of perinatal transmission of HIV. Non–HIV-infected individuals who receive nevirapine are at risk for the development of severe and potentially life-threatening cutaneous and hepatic toxicity. Although precise estimates of the risk for severe hepatotoxicity are not available, the risk appears to be higher than in HIV-infected persons and may be associated with higher CD4 counts. Therefore non–HIV-infected individuals should not receive PEP or other prophylaxis regimens that include multiple doses of nevirapine.
1. Murphy RL. Non-nucleoside reverse transcriptase inhibitors. AIDS Clin Care. 1997; 9:75–79.
2. De Clercq E. HIV inhibitors targeted at the reverse transcriptase. AIDS Res Hum Retroviruses. 1992; 8:119–134.
3. Lamson MJ, Sabo JP, MacGregor TR, et al. Single dose pharmacokinetics and bioavailability of nevirapine in healthy volunteers. Biopharm Drug Dispos. 1999; 20:285–291.
4. Easterbrook PJ, Newson R, Ives N, et al. Comparison of virologic, immunologic, and clinical response to five different initial protease inhibitor-containing and nevirapine -containing regimens. J Acquir Immune Defic Syndr. 2001; 27:350–364.
5. Pollard RB, Robinson P, Dransfield K. Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. Clin Ther. 1998; 20:1071–1092.
6. Montaner JS, Hall D, Carlier H, et al. Analyses of four clinical trials to assess the risk of hepatotoxicity with nevirapine: correlation with CD4+ levels, hepatitis B and C seropositivity, and baseline liver function tests. Can J Infect Dis. 2001; 12(Suppl B):31B.
7. Centers for Disease Control and Prevention. Serious adverse events attributed to nevirapine regimens for post-exposure prophylaxis after HIV exposures worldwide, 1997–2000. MMWR Wkly Rep. 2001; 49:1153–1156.
8. Johnson S, Baraboutis JG. Adverse effects associated with use of nevirapine in HIV postexposure prophylaxis for 2 health care workers. JAMA. 2000; 284:2722–2723.
9. Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures worldwide, 1997–2000. MMWR Wkly Rep. 2001; 49:1153–1156.
10. Sha BE, Proia LA, Kessler HA. Adverse effects associated with use of nevirapine in HIV postexposure prophylaxis for 2 health care workers. JAMA. 2000; 284:2722–2723.
11. Benn PD, Mercey DE, Brink N, et al. Prophylaxis with a nevirapine-containing triple regimen after exposure to HIV-1. Lancet. 2001; 357:687–688.
12. Leitze Z, Nadeem A, Chodhay A, et al. Nevirapine-induced hepatitis treated with corticosteroids? AIDS. 1998; 12:1115–1117.
13. Ziol M, Ganne-Carrie N, Christidis C, et al. Non-alcoholic steatohepatitis in HIV and HCV infected patients treated by antiretroviral tritherapy. J Hepatol. 1999; 30(Suppl):S239.
14. Jarrouse B, Cohen P, Berlureua P, et al. Nevirapine-induced fulminant hepatitis: presentation of case and analysis of risk factors. In: Proceedings of the Seventh European Conference on Clinical Aspects and Treatment of HIV Infection. Lisbon, Portugal; 1999:23–27.
15. Cattelan AM, Erne E, Saltino A, et al. Severe hepatic failure related to nevirapine treatment. Clin Infect Dis. 1999; 29:455–456.
16. Johnson S, Chan J, Bennett CL. Hepatotoxicity after prophylaxis with a nevirapine containing anti-retroviral regimen. Ann Intern Med. 2002; 137:146–147.
17. Burt AD, Mutton A, Day CP. Diagnosis and interpretation of steatosis and steatohepatitis. Semin Diagn Pathol. 1998; 15:246–258.
18. Brinkman K, ter Hofstede HJM, Burger DM, et al. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS. 1998; 12:1735–1744.
19. Bissel MD, Gores JG, Laskin DL, et al. Drug-induced liver injury: mechanisms and test systems. Hepatology. 2001; 33:1009–1113.
20. Sissoko D, Ajana F, de la Tribonniere X, et al. Cutaneous, hepatic, and hematologic manifestations due to nevirapine: DRESS syndrome? Presse Med. 2000; 29:1041–1042.
21. Pilero PJ, Purdy B. Nevirapine-associated hepatitis: a case series and review of the literature. AIDS Reader. 2001; 11:379–382.
22. Bundrow D, Rosoff L, Abaloufia DM. Optimal treatment of nevirapine-associated hepatotoxicity remains uncertain. AIDS Reader. 2001; 11:577–580.
23. Prendville J, Hebert A, Greenwald M, et al. Management of Stevens-Johnson syndrome and toxic epidermal necrolysis. Lancet. 1998; 352:1586–1589.
24. Leitze Z, Nadeem A, Coudhary A, et al. Nevirapine-associated hepatitis treated with corticosteroids? AIDS. 1998; 12:1115–1117.
25. Bourezane Y, Salard D, Hoen B, et al. DRESS (drug rash with eosinophilia and systemic symptoms) syndrome associated with nevirapine therapy. Clin Infect Dis. 1998; 27:1321–1322.
26. Harris M, Montaner JSG. Editorial comment: nevirapine hepatotoxicity—an important clinical issue. AIDS Reader. 2001; 11:580.
27. Kessler DA. Introducing MedWatch: a new approach to reporting medication and device adverse effects and product problems. JAMA. 1993; 269:2765–2768.
28. Temple R. Meta-analysis and epidemiologic studies in drug development and post-marketing surveillance. JAMA. 1999; 281:841–844.
29. Bennett CL, Kiss JE, Weinberg PD, et al. Thrombotic thrombocytopenic purpura after stenting and ticlopidine. Lancet. 1998; 352:1036–1037.
30. Montaner JS, Cahn P, Zala C, et al. 1100.1286 Study Team. Randomized, controlled study of the effects of a short course of prednisone on the incidence of rash associated with nevirapine in patients infected with HIV-1. J Acquir Immune Defic Syndr. 2003; 33:41–46.
31. Knobel H, Miro JM, Domingo P, et al. Failure of a short-term prednisone regimen to prevent nevirapine-associated rash: a double-blind placebo-controlled trial: the GESIDA 09/99 study. J Acquir Immune Defic Syndr. 2001; 28:14–18.
32. Bennett CL, Connors JM, Carwile JM, et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med. 2000; 342:1773–1777.
This article has been cited 57 time(s).
Chemical Research in Toxicology12-OH-Nevirapine Sulfate, Formed in the Skin, Is Responsible for Nevirapine-Induced Skin RashChemical Research in Toxicology
Chemical Research in ToxicologyDetection of Drug Bioactivation in Vivo: Mechanism of Nevirapine-Albumin Conjugate Formation in PatientsChemical Research in Toxicology
Hypersensitivity reactions to antiretroviral agents in HIV-infected patients
Medicina Clinica, 128(2):
PharmacogenomicsPharmacogenetic information derived from analysis of HLA allelesPharmacogenomics
The impact of human genetic variation on HIV disease in the era of HAART
AIDS Reviews, 8(2):
Annals of PharmacotherapyIncreased adverse drug reactions to antimicrobials and anticonvulsants in patients with HIV infectionAnnals of Pharmacotherapy
Liver transplantation for fulminant hepatitis related to nevirapine therapy
Liver Transplantation, 12():
British Journal of Clinical Pharmacology
Bioactivation of nevirapine: characterization and quantification of nevirapine mercapturate in human urine
British Journal of Clinical Pharmacology, 68(2):
Journal of Pharmacology and Experimental TherapeuticsRitonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytesJournal of Pharmacology and Experimental Therapeutics
HepatologyHIV and liver disease forum: Conference proceedingsHepatology
British Journal of Clinical Pharmacology
Bioactivation of nevirapine: characterization and quantification of nevirapine mercapturate in human urine
British Journal of Clinical Pharmacology, 68(2):
Current Opinion in Drug Discovery & Development
The sulfonamide group as a structural alert: A distorted story?
Current Opinion in Drug Discovery & Development, 11(1):
Antimicrobial Agents and ChemotherapyInteraction between fosamprenavir, with and without ritonavir, and nevirapine in human immunodeficiency virus-infected subjectsAntimicrobial Agents and Chemotherapy
Dermatologic ClinicsAdverse cutaneous drug eruptions and HIV: a clinician's global perspectiveDermatologic Clinics
Pharmacogenetics of antiretroviral therapy: genetic variation of response and toxicity
Clinical Infectious Diseases
Hepatic safety and postexposure prophylaxis
Clinical Infectious Diseases, 39(7):
Risk of side effects associated with the use of nevirapine in treatment-naive patients, with respect to gender and CD4 cell count
HIV Medicine, 9(1):
New England Journal of Medicine
Postexposure Prophylaxis for HIV Infection
New England Journal of Medicine, 361():
American Journal of TransplantationNevirapine-Induced Stevens Johnson-Syndrome and Fulminant Hepatic Failure Requiring Liver TransplantationAmerican Journal of Transplantation
Determinants of nevirapine hypersensitivity and its effect on the association between hepatitis C status and mortality in antiretroviral drug-naive HIV-positive patients
Jama-Journal of the American Medical Association
The Rresearch on Adverse Drug Events and Reports (RADAR) project
Jama-Journal of the American Medical Association, 293():
PharmacogenomicsPredicting and diagnosing abacavir and nevirapine drug hypersensitivity: from bedside to bench and back againPharmacogenomics
Journal of VirologyGenetic analysis of simian immunodeficiency virus expressed in milk and selectively transmitted through breastfeedingJournal of Virology
HautarztRashes in M-infected patients undergoing therapy with nevirapine or efavivenzHautarzt
Annual Review of Pharmacology and ToxicologyPharmacogenetics of anti-HIV drugsAnnual Review of Pharmacology and Toxicology
Maternal hepatotoxicity with nevirapine as part of combination antiretroviral therapy in pregnancy
HIV Medicine, 7(4):
International Journal of Std & AIDS
International Journal of Std & AIDS, 17(6):
Infection Control and Hospital Epidemiology
Fatigue increases the risk of injury from sharp devices in medical trainees: Results from a case-crossover study
Infection Control and Hospital Epidemiology, 28(1):
First-line antiretroviral therapy in Africa - How evidence-based are our recommendations?
AIDS Reviews, 7(3):
HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients
ToxicologyCharacterization and Quantification of Mercapturate and Glutathione Conjugates of NevirapineToxicology
Intracellular Pharmacokinetics of Antiretroviral Drugs in HIV-Infected Patients, and their Correlation with Drug Action
Clinical Pharmacokinetics, 49(1):
The use of a triple nucleoside-nucleotide-regimen for occupational HIV post-exposure prophylaxis
HIV Medicine, 6(3):
Chemical Research in ToxicologyEvidence of an immune-mediated mechanism for an idiosyncratic nevirapine-induced reaction in the female brown Norway ratChemical Research in Toxicology
ChemotherapyNevirapine toxicity in non-HIV cancer patientsChemotherapy
Current Opinion in Molecular Therapeutics
Nevirapine hypersensitivity reaction: Will the real HLA please stand up?
Current Opinion in Molecular Therapeutics, 11(3):
Cell differentiation and iodine-131 uptake in poorly differentiated thyroid tumour in response to nevirapine
Lancet Oncology, 7():
Infection Genetics and EvolutionPharmacogenetics of antiretroviral drugs for the treatment of HIV-infected patients: An updateInfection Genetics and Evolution
Medizinische KlinikHIV infection 2007Medizinische Klinik
Drug Metabolism and DispositionQuantifying the Metabolic Activation of Nevirapine in Patients by Integrated Applications of NMR and Mass SpectrometriesDrug Metabolism and Disposition
Pharmacogenetics of Adverse Effects Due To Antiretroviral Drugs
AIDS Reviews, 12(1):
Annales De Pathologie
Mitochondrial hepatic toxicity associated with antiretroviral treatment
Annales De Pathologie, 25(4):
HepatologyGrowing importance of liver disease in HIV-infected personsHepatology
HIV Clinical Trials
Prospective, open-label comparative study of liver toxicity in an unselected population of HIV-infected patients treated for the first time with efavirenz or nevirapine
HIV Clinical Trials, 6(6):
Archives of Internal Medicine
Evaluation of serious adverse drug reactions - A proactive pharmacovigilance program (RADAR) vs safety activities conducted by the Food and Drug Administration and pharmaceutical manufacturers
Archives of Internal Medicine, 167():
Drug SafetyResults from the First Decade of Research Conducted by the Research on Adverse Drug Events and Reports (RADAR) ProjectDrug Safety
Current Opinion in Allergy and Clinical ImmunologyDrug hypersensitivity in HIVCurrent Opinion in Allergy and Clinical Immunology
Current Opinion in GastroenterologyDrug-induced liver disease 2004Current Opinion in Gastroenterology
Current Opinion in Infectious DiseasesPostexposure prophylaxis after sexual exposure to HIVCurrent Opinion in Infectious Diseases
Current Opinion in Infectious DiseasesProtection of healthcare workers from bloodborne pathogensCurrent Opinion in Infectious Diseases
Current Opinion in OncologyAntiretroviral therapy: an update for the non-AIDS specialistCurrent Opinion in Oncology
JAIDS Journal of Acquired Immune Deficiency SyndromesTolerance of a Short Course of Nevirapine, Associated With 2 Nucleoside Analogues, in Postexposure Prophylaxis of HIVJAIDS Journal of Acquired Immune Deficiency Syndromes
hepatotoxicity; drug reaction skin; drug reaction liver; HIV; AIDS; postmarketing drug surveillance; nevirapine; hypersensitivity reaction; postexposure prophylaxis; hepatitis
© 2004 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Highlight selected keywords in the article text.
Data is temporarily unavailable. Please try again soon.