title: Conservation of first-line antiretroviral treatment regimen where therapeutic options are limited.
abstract: OBJECTIVE
  To determine rates and causes of switching from first- to second-line antiretroviral treatment (ART) regimens in a large treatment-naive cohort (a South African community-based ART service) where a targeted adherence intervention was used to manage initial virological breakthrough.
  
  
  METHODS
  ART-naive adults (n=929) commencing first-line non-nucleoside-based ART [according to WHO (2002) guidelines] between September 2002 and August 2005 were studied prospectively. Viral load (VL) and CD4+ T-cell counts were monitored every 4 months. All drug switches were recorded. Counsellor-driven adherence interventions were targeted to patients with a VL > 1000 copies/ml at any visit (virological breakthrough) and the VL measurement was repeated within 8 weeks. Two consecutive VL measurements > 1000 copies/ml was considered virological failure, triggering change to a second-line regimen.
  
  
  RESULTS
  During 760 person-years of observation [median (IQR) 189 (85-441) days], 823 (89%) patients were retained on ART, 2% transferred elsewhere, 7% died and 3% were lost to follow-up. A total of 893 (96%) patients remained on first-line therapy and 16 (1.7%) switched to second-line due to hypersensitivity reactions (n=9) or lactic acidosis (n=7). A Kaplan-Meier estimate for switching to second-line due to toxicity was 3.0% at 32 months. Virological breakthrough occurred in 67 (7.2%) patients, but, following use of a targeted adherence intervention, virological failure was confirmed in just 20 (2.2%). Kaplan-Meier estimates at 32 months were 20% for virological breakthrough but only 5.6% for confirmed virological failure.
  
  
  CONCLUSIONS
  Regimen switches were due to virological failure or toxicity. Although follow-up time was limited, over 95% of individuals remained on first-line ART using a combination of viral monitoring and a targeted adherence intervention.
authors.affiliation: The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa. catherine.orrell@hiv-research.org.za
authors.forename: Catherine
authors.initials: C
authors.lastname: Orrell
authors.forename: Guy
authors.initials: G
authors.lastname: Harling
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
authors.forename: Richard
authors.initials: R
authors.lastname: Kaplan
authors.forename: Matthew
authors.initials: M
authors.lastname: McNally
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003153:Community Health Services / Q000706:statistics & numerical data; D003376:Counseling / Q000706:statistics & numerical data; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D006297:Health Services Accessibility / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D010349:Patient Compliance / Q000706:statistics & numerical data; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral