title: Effectiveness and metabolic complications after 96 weeks of a generic fixed-dose combination of stavudine, lamivudine, and nevirapine among antiretroviral-naive advanced HIV-infected patients in Thailand: A prospective study.
abstract: BACKGROUND
  Generic fixed-dose combination (FDC) antiretroviral therapy (ART) has been widely used in resource-limited settings. Treatment based on these combinations provide low pill burden and are less expensive.
  
  
  OBJECTIVE
  The aim of this study was to determine the long-term effectiveness and metabolic complications of a generic FDC of stavudine (d4T)/lamivudine (3TC)/ nevirapine (NVP), among ART-naive HIV-infected patients.
  
  
  METHODS
  A prospective study was conducted among patients who were initiated on d4T/3TC/NVP between November 2004 and March 2005. Plasma HIV-1 RNA, CD4 and alanine transaminase were assessed every 12 weeks. Fasting plasma glucose (FPG) and lipid profile were determined at 96 weeks. Adverse events and genotypic drug resistance were recorded. The primary outcome of interest was the proportion of patients who achieved plasma HIV-1 RNA <50 copies/mL after 96 weeks of ART and analyzed by intent-to-treat (ITT) and on-treatment (OT) populations.
  
  
  RESULTS
  There were 140 patients (mean [SD] age, 35.7 [7.6] years; male, 67.9%) enrolled in the study. Median (interquartile range [IQR]) baseline CD4 was 31 (14-79) cells/mm(3) and HIV-1 RNA count was 433,500 (169,000-750,000) copies/mL. At week 96, 87 patients (ITT, 62.1%; OT, 87.0%) achieved HIV-1 RNA -50 copies/mL. Median (IQR) CD4 at 96 weeks was 328 (229-450) cells/mm(3). The reasons for drug discontinuation were as follows: drug resistance (9.3%), lost to follow-up (9.3%), NVP- related rashes (7.9%), death (5.0%), d4T-related adverse events (3.6%), and transferred to another hospital (2.1%). At 96 weeks, 25 patients (28.7%) had low-density lipoprotein cholesterol (LDL-C) >130 mg/dL, 7 (8.0%) had LDL-C >160 mg/dL, 6 (6.9%) had triglycerides >400 mg/dL, and 2 (2.3%) had FPG >126 mg/dL. Eleven patients (12.6%) had a lactic acid level >2.5 mmol/L. Eight patients (9.2%) needed to take antihypertensive agents. Of 13 patients who developed virologic failure, 76.9% and 61.5% had M184V/I and Y181C/I mutations, respectively.
  
  
  CONCLUSIONS
  Initiation of this FDC ofd4T/3TC/NVP in these ART-naive patients with advanced HIV infection and low baseline CD4 cell count was effective at 96 weeks of follow-up with regard to virologic and immunologic responses. However, long-term metabolic complications, particularly dyslipidemia, were common and should be closely monitored.
authors.affiliation: Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand ; Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Weerawat
authors.initials: W
authors.lastname: Manosuthi
authors.affiliation: Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Somnuek
authors.initials: S
authors.lastname: Sungkanuparph
authors.affiliation: Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Somsit
authors.initials: S
authors.lastname: Tansuphaswadikul
authors.affiliation: Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Wisit
authors.initials: W
authors.lastname: Prasithsirikul
authors.affiliation: Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Chatiya
authors.initials: C
authors.lastname: Athichathanabadi
authors.affiliation: Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Sirirat
authors.initials: S
authors.lastname: Likanonsakul
authors.affiliation: Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Achara
authors.initials: A
authors.lastname: Chaovavanich
keywords: GPOvir-S; HIV; effectiveness; metabolic; nevirapine