Objectives: To determine the incidence and risk factors for nevirapine (NVP)-associated toxicity in a cohort of HIV-infected people in Buenos Aires, Argentina. Design: Retrospective study. Methods: HIV-infected adults who received NVP-based highly active antiretroviral therapy (HAART) at least for 2 weeks between May 1997 and March 2008 were included in this study. We analyzed patients’ age, gender, HIV transmission route, HIV disease stage, pregnancy, alcohol intake, adverse events, coinfection with hepatitis B or C virus, time until toxicity, and withdrawal rates. Results: A total of 1110 patients (631 men) were included. Rash was the most frequently observed adverse event; it was more frequent in women. The incidence of severe rash and hepatotoxicity was similar in women and men. Female sex was the only variable significantly associated with mild-to-moderate rash. High CD4 count, pregnancy, and chronic hepatitis were not associated with NVP-related toxicity. An undetectable viral load at the time of starting NVPtreatment resulted in a lower risk of NVP-related rash.
Panel on Antiretroviral Guidelines for Adult and Adolescents.Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. December 1, 2009; 1-161. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf. Accessed December 2, 2009.
2.
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(6):1071-1092.
3.
Taiwo BONevirapine toxicity. Int J STD & AIDS. 2006;17(6): 364-370.
4.
Stern JO, Robinson PA, Love J., Lanes S., Imperiale MS, Mayers DLA comprehensive hepatic safety analysis of nevirapine in different populations of HIV infected patients. J Acquir Immune Defic Syndr. 2003;34(suppl 1):S21-S33.
5.
Ena J., Amador C., Benito C., Fenoll V., Pasquau F.Risk and determinants of developing severe liver toxicity during therapy with nevirapine-and efavirenz-containing regimens in HIV-infected patients. Int J STD AIDS. 2003;14(11):776-781.
6.
Baylor M., Truffa M., Gibbs N.Hepatic toxicity of antiretrovirals in HIV-infected pregnant women: a review of the FDA’s adverse event reporting system. In 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA, February 2004 (Abstract 944).
7.
US Department of Health & Human Services.FDA Public Health Advisory for Nevirapine (Viramune). http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm051674.htm . Accessed December 2, 2009.
8.
Centers for Disease Control and Prevention.1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults . MMWR Recomm Rep1. 1992;41(RR-17):1-19.
9.
O’Connor PGAlcohol Abuse and Dependence. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. St. Louis, MO: WB Saunders Company, 2004:17.
10.
Saunders JB , Aasland OG, Babor TF, de La Fuente JR, Grant M.Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption-II. Addiction. 1993; 88(6):791-804.
11.
Montaner JS , Reiss P., Cooper D., et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study. JAMA. 1998;279(12): 930-937.
12.
D’Aquila RT, Hughes MD, Johnson VA, et al. Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group Protocol 241 Investigators . Ann Intern Med. 1996;124(12):1019-1030.
13.
Kesselring AM, Wit FW, Sabin CA, et al. Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy . AIDS.2009;23(13):1689-1699.
14.
Mazhude C., Jones S., Murad S., Taylor C., Easterbrook P.Female sex but not ethnicity is a strong predictor of non-nucleoside reverse transcriptase inhibitor-induced rash. AIDS. 2002;16(11): 1566-1568.
15.
Bersoff-Matcha SJ, Miller WC, Aberg JA, et al. Sex differences in nevirapine rash . Clin Infect Dis. 2001;32(1):124-129.
16.
Bonnet F., Lawson-Ayayi S., Thiébaut R., et al. A cohort study of nevirapine tolerance in clinical practice: French Aquitaine Cohort, 1997-1999. Clin Infect Dis. 2002;35(10):1231-1237.
17.
Zhou J., Phanupak P., Kiertiburanakul S., et al. Highly active antiretroviral treatment containing efavirenz or nevirapine and related toxicity in the TREAT Asia HIV observational database . J Acquir Immune Defic Syndr. 2006;43(4):501-502. (Letter).
18.
Tansuphaswadikul S., Aung SE, Phonrat B., Kaewkungwal J., Pitisuttithum P., Maek-a-nantawat W.Presisposing factors for nevirapine toxicity among AIDS patients with low baseline CD4 count. Asian Pac J Allergy Immunol. 2007;25(2-3):147-154.
19.
Sanne I., Mommeja-Marin H., Hinkle J., et al. Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects. J Infect Dis. 2005;191(6):825-829.
20.
van Griensven J., Zachariah R., Rasschaert F., Mugabo J., Atté EF, Reid T.Stavudine-and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment incidence timing and risk factors in a three-year cohort in Kigali, Rwanda. Trans R Soc Trop Med Hyg.2010;104(2):148-153.
21.
Jamisse L., Balkus J., Hitti J., et al. Antiretroviral-associated toxicity among HIV-1-seropositive pregnant women in Mozambique receiving nevirapine-based regimens. J Acquir Immune Defic Syndr. 2007;44(4):371-376. (Letter).
22.
Gatanaga H. , Yazaki H., Tanuma J., et al. HLA-Cw8 primarily associated with hypersensitivity to nevirapine. AIDS. 2007 ; 21(2):264-265. (Letter).
23.
Vitezica ZG, Milpied B., Lonjou C., et al. HLA-DRB1*01 associated with cutaneous hypersensitivity induced by nevirapine and efavirenz. AIDS. 2008;22(4):540-541. (Letter).
24.
Haas DW, Bartlett JA, Andersen JW, et al. Pharmacogenetics of nevirapine-associated hepatotoxicity: an adult AIDS Clinical Trials Group Collaboration. Clin Infect Dis. 2006;43(6):783-786.
25.
Sulkowski MS, Thomas DL, Mehta SH, Chaisson RE, Moore RDHepatotoxicity associates with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infection. Hepatology. 2002;35(1):182-189.
26.
Snijdewind I., Smit C., Godfried M., et al. Side effects of HAART in HIV-1-infected pregnant and non-pregnant women: pregnancy is associated with hepatotoxicity, while ethnicity is associated with rash. In 16th Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009. Montreal, Canada (Abstract 948).
27.
Knobel H., Guelar A., Montero M., et al. Risk of side effects associated with the use of nevirapine in treatment-naïve patients, with respect to gender and CD4 cell count. HIV Med. 2008;9(1):14-18.
28.
Manfredi R. , Calza L.Nevirapine versus efavirenz in 742 patients: no link of liver toxicity with female sex, and a baseline CD4 cell count greather than 250 cells/μl. AIDS. 2006;20(17):2233-2236.
29.
Phillips E. , Gutiérrez S., Jahnke N., et al. Determinants of nevirapine hypersensitivity and its effect on the association between hepatitis C status and mortality in antiretroviral drug-naive HIV-positive patients . AIDS. 2007;21(12):1561-1568.
30.
Aaron E., Kempf M., Criniti S., et al. Risks associated with nevirapine use in pregnant and non-pregnant women. In 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston (MA), USA. (Abstract 983).
31.
João EC, Calvet GA, Menezes JA, et al. Nevirapine toxicity in a cohort of HIV-1-infected pregnant women. Am J Obstet Gynecol. 2006;194(1):199-202.
32.
Kondo W., Astori Ade A., Gomes Sel-K, Fernandes Rde B., Sasaki MG, Sbalqueiro RLEvaluation of the adverse effects of nevirapine in HIV-infected pregnant women in a South Brazilian University Hospital. Rev Bras Ginecol Obstet. 2008;30(1):19-24.
33.
Wolf E., Koegl C., Theobald T.Nevirapine-associated hepatotoxicity: No increased risk for females or high CD4 count in a single centre HIV cohort. In 46th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Francisco CA. 2006 (Abstract H-1063).
34.
Lyons F., Hopkins S., Kelleher B., et al. Maternal hepatotoxicity with nevirapine as part of combination antiretroviral therapy in pregnancy. HIV Med. 2006;7(4):255-260.
35.
Phanuphak N. , Apornpong T., Teeratakulpisarn S., et al. Nevirapine-associated toxicity in HIV-infected Thai men and women, including pregnant women. HIV Med. 2007;8(6):357-366.
36.
Hitti J., Frenkel LM, Stek AM, et al. Maternal toxicity with continuous nevirapine in pregnancy: results from PACTG 1022. J Acquir Immune Defic Syndr. 2004;36(3):772-776.
37.
Marazzi MC, Germano P., Liotta G., et al. Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. HIV Med. 2006;7(5):338-344.
38.
Ouyang DW, Brogly SB, Lu M., et al. Lack of increased hepatotoxicity in HIV-infected pregnant women receiving nevirapine compared with other antiretrovirals. AIDS.2010;24(1):109-114.
39.
Ouyang DW, Shapiro DE, Lu M., et al. Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure. AIDS.2009;23(18): 2425-2430.
40.
Rey J., Dugoujon JM, Dejean C., Carnese FRGene mixture in a population sample from Buenos Aires City. Medicina (Buenos Aires). 2006;66(2):113-118.
