PMID- 23362284
OWN - NLM
STAT- MEDLINE
DCOM- 20130913
LR  - 20211021
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 56
IP  - 9
DP  - 2013 May
TI  - Association of human leukocyte antigen alleles and nevirapine hypersensitivity in 
      a Malawian HIV-infected population.
PG  - 1330-9
LID - 10.1093/cid/cit021 [doi]
AB  - BACKGROUND: The nonnucleoside reverse transcriptase inhibitor nevirapine is the 
      cornerstone of treatment for human immunodeficiency virus (HIV) in many 
      sub-Saharan African countries. However, nevirapine is associated with a 6%-10% 
      risk of developing a hypersensitivity reaction, with different phenotypes, 
      including the blistering conditions Stevens-Johnson syndrome (SJS) and toxic 
      epidermal necrolysis (TEN). Our aim was to identify predictive human leukocyte 
      antigen (HLA) markers that are associated with nevirapine hypersensitivity. 
      METHODS: We identified 117 HIV-infected Malawian adults with nevirapine 
      hypersensitivity (15 drug-induced liver injury [DILI], 33 SJS/TEN, 20 
      hypersensitivity syndrome, and 46 nevirapine-induced rash plus 3 with both DILI 
      and SJS phenotype) and 155 age-, sex- and ethnicity-matched nevirapine-exposed 
      controls. HLA typing for 5 loci (A, B, C, DRB1, and DQB1) was undertaken using a 
      sequence-based high-resolution protocol. Logistic regression analysis included 
      CD4(+) cell count as a covariate. RESULTS: HLA-C*04:01 was found to markedly 
      increase the risk for SJS (odds ratio [OR] = 17.52; 95% confidence interval, 
      3.31-92.80) and all hypersensitivity phenotypes (OR = 2.64; 95% CI, 1.13-6.18) 
      when compared to the baseline rare allele group in a binary logistic regression 
      model. The OR for absolute risk of SJS/TEN associated with carriage of 
      HLA-C*04:01 was 5.17 (95% CI, 2.39-11.18). Positive predictive value was 2.6% and 
      negative predictive value was 99.2%. In addition, a number of alleles within the 
      HLA-DQB1 loci protected against nevirapine-induced hypersensitivity phenotypes. 
      CONCLUSIONS: Our study has identified HLA-C*04:01 carriage as a risk factor for 
      nevirapine-induced SJS/TEN in a Malawian HIV cohort. Validation of these findings 
      in a larger cohort of patients and mechanistic investigation of the pathogenesis 
      are required.
FAU - Carr, Daniel F
AU  - Carr DF
AD  - Department of Molecular and Clinical Pharmacology, University of Liverpool, 
      United Kingdom.
FAU - Chaponda, Mas
AU  - Chaponda M
FAU - Jorgensen, Andrea L
AU  - Jorgensen AL
FAU - Castro, Elena Cornejo
AU  - Castro EC
FAU - van Oosterhout, Joep J
AU  - van Oosterhout JJ
FAU - Khoo, Saye H
AU  - Khoo SH
FAU - Lalloo, David G
AU  - Lalloo DG
FAU - Heyderman, Robert S
AU  - Heyderman RS
FAU - Alfirevic, Ana
AU  - Alfirevic A
FAU - Pirmohamed, Munir
AU  - Pirmohamed M
LA  - eng
GR  - 100890/Wellcome Trust/United Kingdom
GR  - 101113/Wellcome Trust/United Kingdom
GR  - 078857MA/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130129
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Genetic Markers)
RN  - 0 (HLA Antigens)
RN  - 99DK7FVK1H (Nevirapine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anti-HIV Agents/*administration & dosage
MH  - Case-Control Studies
MH  - Drug Hypersensitivity/*genetics
MH  - Female
MH  - Gene Frequency
MH  - Genetic Markers
MH  - HIV Infections/drug therapy
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Malawi
MH  - Male
MH  - Nevirapine/*adverse effects
MH  - Sequence Analysis, DNA
MH  - Young Adult
PMC - PMC3616517
EDAT- 2013/01/31 06:00
MHDA- 2013/09/14 06:00
PMCR- 2013/01/29
CRDT- 2013/01/31 06:00
PHST- 2013/01/31 06:00 [entrez]
PHST- 2013/01/31 06:00 [pubmed]
PHST- 2013/09/14 06:00 [medline]
PHST- 2013/01/29 00:00 [pmc-release]
AID - cit021 [pii]
AID - 10.1093/cid/cit021 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2013 May;56(9):1330-9. doi: 10.1093/cid/cit021. Epub 2013 Jan 
      29.