HLA-Cw*04 Allele Associated with Nevirapine-induced Rash in HIV-infected Thai Patients

Overview

Journal AIDS Res Ther

Publisher Biomed Central

Specialty Infectious Diseases

Date 2009 Oct 23

PMID 19845952

Citations 33

Authors

Sirirat Likanonsakul

Tippawan Rattanatham

Siriluk Feangvad

Sumonmal Uttayamakul

Wisit Prasithsirikul

Preecha Tunthanathip

Emi E Nakayama

Tatsuo Shioda

Affiliations

Soon will be listed here.

Abstract

Background: A high incidence of rash has been reported in HIV-1 patients who received the anti-retroviral drug nevirapine. In addition, several studies have suggested that polymorphisms of human leukocyte antigen (HLA) genes may play important roles in nevirapine-induced rash. The aim of the present study was to evaluate the effects of different HLA-C alleles on rash associated with nevirapine in patients who started highly active anti-retroviral therapy (HAART) containing nevirapine in Thailand.

Results: A case-control study was carried out involving HIV-1 patients under treatment at Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand between March 2007 and March 2008. The study included all HIV/AIDS patients being treated with nevirapine-containing regimens. The study population comprised 287 HIV/AIDS patients of whom 248 were nevirapine-tolerant and 39 developed rash after nevirapine treatment. From the nevirapine-tolerant patients, 60 were selected as the control group on the basis of age, sex, and therapy history matched for nevirapine-induced rash cases. We observed significantly more HLA-Cw*04 alleles in nevirapine-induced rash cases than in nevirapine-tolerant group, with frequencies of 20.51% and 7.50%, respectively (P = 0.009). There were no significant differences between the rash and tolerant groups for other HLA-C alleles except for HLA-Cw*03 (P = 0.015).

Conclusion: This study suggests that HLA-Cw*04 is associated with rash in nevirapine treated Thais. Future screening of patients' HLA may reduce the number of nevirapine-induced rash cases, and patients with alleles associated with nevirapine-induced rash should be started on anti-retroviral therapy without nevirapine.

Citing Articles

Pharmacogenomic landscape of the Thai population from genome sequencing of 949 individuals.

Piriyapongsa J, Chumnumwat S, Kaewprommal P, Triparn K, Suvichapanich S, Udomsinprasert W Sci Rep. 2024; 14(1):30683.

PMID: 39730427 PMC: 11681108. DOI: 10.1038/s41598-024-79018-6.

Delayed Drug Hypersensitivity Reactions: Molecular Recognition, Genetic Susceptibility, and Immune Mediators.

Chu M, Chang W, Pao S, Hung S Biomedicines. 2023; 11(1).

PMID: 36672685 PMC: 9855900. DOI: 10.3390/biomedicines11010177.

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS)/Drug-Induced Hypersensitivity Syndrome (DiHS)-Readdressing the DReSS.

Stirton H, Shear N, Dodiuk-Gad R Biomedicines. 2022; 10(5).

PMID: 35625735 PMC: 9138571. DOI: 10.3390/biomedicines10050999.

Genetic testing for prevention of severe drug-induced skin rash.

Alfirevic A, Pirmohamed M, Marinovic B, Harcourt-Smith L, Jorgensen A, Cooper T Cochrane Database Syst Rev. 2019; 7:CD010891.

PMID: 31314143 PMC: 6636675. DOI: 10.1002/14651858.CD010891.pub2.

Associations between human leukocyte antigen polymorphisms and hypersensitivity to antiretroviral therapy in patients with human immunodeficiency virus: a meta-analysis.

Hu K, Xiang Q, Wang Z, Mu G, Zhang Z, Ma L BMC Infect Dis. 2019; 19(1):583.

PMID: 31277607 PMC: 6612203. DOI: 10.1186/s12879-019-4227-5.

References

Martin A, Nolan D, James I, Cameron P, Keller J, Moore C . Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS. 2005; 19(1):97-9. DOI: 10.1097/00002030-200501030-00014. View

Manosuthi W, Sungkanuparph S, Tansuphaswadikul S, Inthong Y, Prasithsirikul W, Chottanapund S . Incidence and risk factors of nevirapine-associated skin rashes among HIV-infected patients with CD4 cell counts <250 cells/microL. Int J STD AIDS. 2007; 18(11):782-6. DOI: 10.1258/095646207782212289. View

Pollard R, Robinson P, Dransfield K . Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. Clin Ther. 1999; 20(6):1071-92. DOI: 10.1016/s0149-2918(98)80105-7. View

Palella Jr F, Delaney K, Moorman A, Loveless M, Fuhrer J, Satten G . Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998; 338(13):853-60. DOI: 10.1056/NEJM199803263381301. View

Cruse J, Brackin M, Lewis R, Meeks W, Nolan R, Brackin B . HLA disease association and protection in HIV infection among African Americans and Caucasians. Pathobiology. 1991; 59(5):324-8. DOI: 10.1159/000163671. View

Pirmohamed M, Park B . HIV and drug allergy. Curr Opin Allergy Clin Immunol. 2002; 1(4):311-6. DOI: 10.1097/01.all.0000011032.69243.10. View

Mallal S, Nolan D, Witt C, Masel G, Martin A, Moore C . Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002; 359(9308):727-32. DOI: 10.1016/s0140-6736(02)07873-x. View

Fellay J, Shianna K, Ge D, Colombo S, Ledergerber B, Weale M . A whole-genome association study of major determinants for host control of HIV-1. Science. 2007; 317(5840):944-7. PMC: 1991296. DOI: 10.1126/science.1143767. View

Kaslow R, Carrington M, Apple R, Park L, Munoz A, Saah A . Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med. 1996; 2(4):405-11. DOI: 10.1038/nm0496-405. View

10.

Carr A, Cooper D . Adverse effects of antiretroviral therapy. Lancet. 2000; 356(9239):1423-30. DOI: 10.1016/S0140-6736(00)02854-3. View

11.

Kiertiburanakul S, Sungkanuparph S, Charoenyingwattana A, Mahasirimongkol S, Sura T, Chantratita W . Risk factors for nevirapine-associated rash among HIV-infected patients with low CD4 cell counts in resource-limited settings. Curr HIV Res. 2008; 6(1):65-9. DOI: 10.2174/157016208783571946. View

12.

Coopman S, Johnson R, Platt R, Stern R . Cutaneous disease and drug reactions in HIV infection. N Engl J Med. 1993; 328(23):1670-4. DOI: 10.1056/NEJM199306103282304. View

13.

Havlir D, Cheeseman S, Mclaughlin M, Murphy R, Erice A, Spector S . High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection. J Infect Dis. 1995; 171(3):537-45. DOI: 10.1093/infdis/171.3.537. View

14.

Anekthananon T, Ratanasuwan W, Techasathit W, Sonjai A, Suwanagool S . Safety and efficacy of a simplified fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-VIR) for the treatment of advanced HIV-infected patients: a 24-week study. J Med Assoc Thai. 2004; 87(7):760-7. View

15.

van Leth F, Andrews S, Grinsztejn B, Wilkins E, Lazanas M, Lange J . The effect of baseline CD4 cell count and HIV-1 viral load on the efficacy and safety of nevirapine or efavirenz-based first-line HAART. AIDS. 2005; 19(5):463-71. DOI: 10.1097/01.aids.0000162334.12815.5b. View

16.

Manosuthi W, Chottanapand S, Thongyen S, Chaovavanich A, Sungkanuparph S . Survival rate and risk factors of mortality among HIV/tuberculosis-coinfected patients with and without antiretroviral therapy. J Acquir Immune Defic Syndr. 2006; 43(1):42-6. DOI: 10.1097/01.qai.0000230521.86964.86. View

17.

Kappelhoff B, van Leth F, MacGregor T, Lange J, Beijnen J, Huitema A . Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study. Antivir Ther. 2005; 10(1):145-55. View

18.

Carrington M, Nelson G, Martin M, Kissner T, Vlahov D, Goedert J . HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science. 1999; 283(5408):1748-52. DOI: 10.1126/science.283.5408.1748. View

19.

Gangar M, Arias G, OBrien J, Kemper C . Frequency of cutaneous reactions on rechallenge with nevirapine and delavirdine. Ann Pharmacother. 2000; 34(7-8):839-42. DOI: 10.1345/aph.19258. View

20.

Sabbatani S, Manfredi R, Biagetti C, Chiodo F . Antiretroviral Therapy in the Real World : Population-Based Pharmacoeconomic Analysis of Administration of Anti-HIV Regimens to 990 Patients. Clin Drug Investig. 2007; 25(8):527-35. DOI: 10.2165/00044011-200525080-00005. View