title: Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen.
abstract: BACKGROUND
  Stavudine-containing antiretroviral regimens are widely used in developing countries. Stavudine-associated lipodystrophy commonly occurs, without a clear predictable pattern owing to the unknown interaction between stavudine and the host, among patients who received this regimen. The aim of this study was to determine the clinical risk factors and human leukocyte antigen (HLA) alleles associated with stavudine-associated lipodystrophy.
  
  
  METHODS
  A case-control, cross-sectional study was conducted for HIV-infected patients receiving stavudine-containing antiretroviral regimens. Clinical assessments for lipodystrophy by physical examination, anthropometry, and dual-energy X-ray absorptiometry were obtained. On the basis of their clinical assessment, the patients were classified into 2 groups: the case group (moderated to severe lipodystrophy) and the control group (absent to mild lipodystrophy). The clinical characteristics and allelic distribution of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 were compared between the case group and the control group, to determine the possible association with stavudine-associated lipodystrophy.
  
  
  RESULTS
  There were 103 patients; 55 patients were in the case group, and 48 patients were in the control group. By use of forward stepwise logistic regression, the presence of HLA-B*4001 (odds ratio [OR], 14.05; 95% confidence interval [CI], 2.57-76.59; P=.002) and a longer duration of stavudine treatment (OR, 1.02; 95% CI, 1.00-1.04; P=.02) were significantly associated with stavudine-associated lipodystrophy, whereas a higher body mass index during treatment (OR, 0.73; 95% CI, 0.61-0.86; P<.001) was associated with a lower risk for lipodystrophy. HLA-B*4001 has a high specificity (95.8%) and a positive predictive value (88.9%) for lipodystrophy.
  
  
  CONCLUSIONS
  HLA-B*4001 is a strong genetic risk factor for stavudine-associated lipodystrophy in HIV-infected patients in Thailand. HLA-B*4001 may be used as a genetic marker to predict which patients will develop stavudine-associated lipodystrophy, to avoid or shorten the duration of stavudine use. This finding needs to be confirmed in further replication studies.
authors.affiliation: Departments of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Wittaya
authors.initials: W
authors.lastname: Wangsomboonsiri
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
authors.forename: Soranun
authors.initials: S
authors.lastname: Chantarangsu
authors.forename: Sasisopin
authors.initials: S
authors.lastname: Kiertiburanakul
authors.forename: Angkana
authors.initials: A
authors.lastname: Charoenyingwattana
authors.forename: Surat
authors.initials: S
authors.lastname: Komindr
authors.forename: Chupong
authors.initials: C
authors.lastname: Thongnak
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Wasun
authors.initials: W
authors.lastname: Chantratita
authors.forename: Somnuek
authors.initials: S
authors.lastname: Sungkanuparph
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001823:Body Composition; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008060:Lipodystrophy / Q000453:epidemiology / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018119:Stavudine / Q000627:therapeutic use*; D013785:Thailand / Q000453:epidemiology
chemical_list: D044966:Anti-Retroviral Agents; D015235:HLA-B Antigens; D018119:Stavudine