1 / 28

Sasisopin Kiertiburanakul , MD, MHS , Surakameth Mahasirimongkol , MD, MSc, PhD,

Late Breaker Track B WELBB04 HLA-B*35:05 and CCHCR1 Screening Reduces Nevirapine -associated Cutaneous Adverse Reactions in Thailand: A Prospective Multicenter Randomized Controlled Trial (NCT 00986063). Sasisopin Kiertiburanakul , MD, MHS , Surakameth Mahasirimongkol , MD, MSc, PhD,

benito
Download Presentation

Sasisopin Kiertiburanakul , MD, MHS , Surakameth Mahasirimongkol , MD, MSc, PhD,

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Late Breaker Track BWELBB04HLA-B*35:05 and CCHCR1 Screening Reduces Nevirapine-associated Cutaneous Adverse Reactions in Thailand: A Prospective Multicenter Randomized Controlled Trial(NCT 00986063) Sasisopin Kiertiburanakul, MD, MHS,SurakamethMahasirimongkol, MD, MSc, PhD, Natta Rajatanavin, MD,AngkanaCharoenyingwattana, BSc (Pharm), MSc, ArchawinRojanawiwat, MD, PhD,WittayaWangsomboonsiri, MD,WeerawatManosuthi, MD,PachareeKantipong, MD,AnuchaApisarnthanarak, MD,WilawanSangsirinakakul, MD,PawineeWongprasit, MD,RomaneeChaiwarith, MD, MHS,WoraphotTantisiriwat, MD, MPH, Michiaki Kubo, MD, PhD, Yusuke Nakamura, MD, PhD, Taisei Mushiroda, PhD,WasunChantratita, PhD, SomnuekSungkanuparph, MD 7th IAS, Kuala Lumpur (July 3, 2013)

  2. Background • Nevirapine (NVP) is the main component of the regimen for the treatment of HIV infection • NVP-based regimen is recommended by EACS and resource-limited settings guidelines including Thailand • NVP-associated cutaneous adverse reaction (NVP-CAR) is a major drug adverse reaction • Prevalence ~15-20% • The associations of NVP-CAR and variations in major histocompatibility complex (MHC) region class I have been reported in Thais • HLA-B*35:05 • Single nucleotide polymorphisms (SNPs) in CCHCR1

  3. HLA-B*35:05 was observed in 17.5% of patients with rash vs. 1.1% of NVP-tolerant patients OR 49.15 (95% CI 6.45-374.41, P=0.00017) Sensitivity 17.5% Specificity 98.9% Chantarangsu S et al. Pharmacogenet Genomics 2009;19:139-46.

  4. ∼550,000 markers • CCHCR1 significantly associated with rash • OR 2.59 (95% CI 1.82-3.68, P=0.007) • Receiver operating characteristic curve showed an area under the curve of 76.4% Chantarangsu S et al. Clin Infect Dis 2011;53:341–8.

  5. Objective • This study was designed to determine the effectiveness of prospective genotypes-based screening to prevent NVP-CAR in HIV-infected Thai patients

  6. Patients and Methods

  7. Study Methods • Prospective multicenter randomized study • 9 hospitals in Thailand • Study period: April 2009-April 2012 • We randomly assigned patients to undergo prospective HLA-B*35:05 and CCHCR1 SNPs genotyping group and control group (standard-of-care group)

  8. Study Methods Prospective-screening group • Exclusion of patients with HLA-B*35:05 and CCHCR1 carrier from using NVP and initiated efavirenz (EFV)-based regimen Control group • NVP usage without prospective genotypic screening End point committee • NVP-CAR was reviewed by central end point committees composed of a clinical immunologist, a dermatologist and an infectious disease specialist Patients were followed for 6 months after ART initiation

  9. Patient Selection Criteria • Age 18-70 years old • Confirmed to be infected with HIV-1 • Naïve to ART • Eligible for ART according to Thai national guidelines • Agreed to withholding other drugs and other medications which do not prescribed by the investigators 14 days prior to ART initiation and during the study • Not a pregnant woman or in a lactation period • AST/ALT <5 ULN

  10. Results

  11. Study Flow Chart • 1,137 patients were enrolled 34 patients did not receive randomization 10 patients withdrew consent 4 patients had a protocol violation 10 patients were lost to follow-up 10 patients were not treated owing to investigator’s decision • Randomized by gender and CD4 strata N=1,103 • Prospective-screening group • N=554 Control group N=549

  12. Baseline Characteristics

  13. Baseline Characteristics (continued)

  14. Antiretroviral Regimens Prospective-screening group Control group

  15. Results *Division of AIDS table for grading the severity of adult and pediatric adverse events

  16. Relative Risk: Overall and By Subgroup

  17. Strength of the Study • First randomized trial regarding personalized prescription of NVP • Point of care genotypic testing is effective preventive intervention for NVP-CAR • NVP can be initiated safely for those who less likely to develop NVP-CAR from the result of genetic testing

  18. Limitations • HLA-B genotype testing may be limited by facility and resource • HLA-B*35:05 is not common in other populations except Southeast Asian and Southern Americans • Additional genetic risks remained to be discovered

  19. Conclusion • HLA-B*35:05 and CCHCR1 SNPs genotypic screening reduced the risk of NVP-CAR • Our results support the use of genotypes-based screening in a clinical setting to prevent NVP-CAR among naïve HIV-infected Thai patients

  20. Acknowledgement • Research grant from Pharmacogenomics Projects, the collaboration between Ramathibodi Hospital, Mahidol University and Thailand Center of Excellence of Life Sciences (TCELS) • All study patients

  21. Sensitivity and Specificity of the Tests

  22. Sensitivity and Specificity of the Tests

  23. Incidence of NVP-CAR

  24. Results of Genetic Testing

  25. Incidence of NVP-CAR

  26. Comparisons of strata by arms Standard of care Genetic testing

  27. Study Team Sasisopin Kiertiburanakul, MD, MHS,1 SurakamethMahasirimongkol, MD, MSc, PhD,2 Natta Rajatanavin, MD,1 AngkanaCharoenyingwattana, BSc (Pharm), MSc,3 ArchawinRojanawiwat, MD, PhD,2 WittayaWangsomboonsiri, MD,4 WeerawatManosuthi, MD,5 PachareeKantipong, MD,6 AnuchaApisarnthanarak, MD,7 WilawanSangsirinakakul, MD,8 PawineeWongprasit, MD,9 RomaneeChaiwarith, MD, MHS,10 WoraphotTantisiriwat, MD, MPH,11 Michiaki Kubo, MD, PhD12 Yusuke Nakamura, MD, PhD,13 Taisei Mushiroda, PhD,13 WasunChantratita, PhD,14SomnuekSungkanuparph, MD1  1Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Thailand 2Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand 3Thailand Center of Excellence for Life Sciences, Mahidol University, Bangkok, Thailand 4Department of Internal Medicine, Sawanpracharak Hospital, Nakornsawan, Thailand 5Department of Internal Medicine, BamrasnaraduraInfectious Disease Institute, Nonthaburi, Thailand 6Department of Internal Medicine, Chiang RaiPrachanukroh Hospital, Chiang Rai, Thailand 7Department of Medicine, Faculty of Medicine, Thammasat University, Pratumthani, Thailand 8Department of Internal Medicine, MaharajNakornratchasima Hospital, Nakornratchasima, Thailand 9Department of Medicine, Buriram Hospital, Buriram, Thailand 10Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand 11Department of Preventive Medicine and Social Medicine, Faculty of Medicine, Srinakharinwirot University, NakhonNayok, Thailand 12Laboratory for Genotyping Development, RIKEN Center for Integrative Medicine Sciences, Yokohama, Japan 13Laboratory for Pharmacogenomic, RIKEN Center for Integrative Medicine Sciences, Yokohama, Japan 14Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Thailand

More Related