title: Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.
abstract: BACKGROUND
  Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand.
  
  
  METHODS
  All HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Cox's proportional hazard models.
  
  
  RESULTS
  Of 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95% CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95% CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95% CI:1.51-2.95). Female gender (aHR 0.54, 95% CI: 0.30-0.96), elder age (aHR 0.56, 95% CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95% CI: 0.10-0.82) were protective for treatment failure related modification.
  
  
  CONCLUSIONS
  HLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and lipodystrophy, respectively. Female gender, elder age, and having HLA-B*40:01 had protective effects on treatment failure-related regimen modification. This study provides further information of regimen modification for future tailored ART in Asia.
authors.affiliation: Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, Japan. lotus0503jp@yahoo.co.jp.|Global COE program, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, Japan. lotus0503jp@yahoo.co.jp.
authors.forename: Naho
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Day Care Center, Lampang Hospital, 280 Paholyothin Road, Muang Lampang, Lampang, 52000, Thailand. panitapa@yahoo.com.
authors.forename: Panita
authors.initials: P
authors.lastname: Pathipvanich
authors.affiliation: National Institute of Health, Ministry of Public Health, 88/7 Tiwanon road, Ampur Muang, Nonthaburi, 11000, Thailand. nuanjunw@yahoo.com.
authors.forename: Nuanjun
authors.initials: N
authors.lastname: Wichukchinda
authors.affiliation: National Institute of Health, Ministry of Public Health, 88/7 Tiwanon road, Ampur Muang, Nonthaburi, 11000, Thailand. archawin191@yahoo.com.
authors.forename: Archawin
authors.initials: A
authors.lastname: Rojanawiwat
authors.affiliation: National Institute of Health, Ministry of Public Health, 88/7 Tiwanon road, Ampur Muang, Nonthaburi, 11000, Thailand. wattana.a@dmsc.mail.go.th.
authors.forename: Wattana
authors.initials: W
authors.lastname: Auwanit
authors.affiliation: Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, Japan. kari@nagasaki-u.ac.jp.|Global COE program, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, Japan. kari@nagasaki-u.ac.jp.
authors.forename: Koya
authors.initials: K
authors.lastname: Ariyoshi
authors.affiliation: Food and Drug Administration, Ministry of Public Health, 88/7 Tiwanon road, Ampur Muang, Nonthaburi, 11000, Thailand. pathom@health.moph.go.th.
authors.forename: Pathom
authors.initials: P
authors.lastname: Sawanpanyalert
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001208:Asia; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D019259:Lamivudine / Q000627:therapeutic use; D008060:Lipodystrophy; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D013785:Thailand; D017211:Treatment Failure
chemical_list: D044966:Anti-Retroviral Agents; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine