title: Rates of switching antiretroviral drugs in a primary care service in South Africa before and after introduction of tenofovir.
abstract: BACKGROUND
  Antiretroviral changes (single drug substitutions and regimen switches) limit treatment options and introduce challenges such as increased cost, monitoring and adherence difficulties. Patterns of drug substitutions and regimen switches from stavudine (d4T) and zidovudine (AZT) regimens have been well described but data on tenofovir (TDF) are more limited. This study describes the patterns and risk factors for drug changes of these antiretroviral drugs in adults.
  
  
  METHODS
  This retrospective cohort study included HIV positive, antiretroviral treatment (ART) naïve adults aged ≥18 years who started ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor. Follow-up was censored at first drug change and analysis focused on NRTI changes only.
  
  
  RESULTS
  Between September 2002 and April 2011, 5095 adults initiated ART in Gugulethu. This comprised 948 subjects on TDF, 3438 on d4T and 709 subjects on AZT. Virological suppression rates at 1 year, regimen switching due to virological failure and overall losses to the programme were similar across the three groups. TDF had the lowest incidence rate of drug substitutions (2.6 per 100 P/Ys) compared to 17.9 for d4T and 8.5 per 100 P/Ys for AZT. Adverse drug reactions (ADRs) accounted for the majority of drug substitutions of d4T. Multivariate analysis showed that increasing age, female sex and d4T exposure were associated with increased hazard of drug substitution due to ADRs. Conversely, TDF exposure was associated with a substantially lower risk of substitution (adjusted hazards ratio 0.38; 95% CI 0.20-0.72).
  
  
  CONCLUSIONS
  Regimen switches and virological suppression were similar for patients exposed to TDF, d4T and AZT, suggesting all regimens were equally effective. However, TDF was better tolerated with a substantially lower rate of drug substitutions due to ADRs.
authors.affiliation: Desmond Tutu HIV Centre, Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. christine_njuguna@yahoo.co.uk
authors.forename: Christine
authors.initials: C
authors.lastname: Njuguna
authors.forename: Catherine
authors.initials: C
authors.lastname: Orrell
authors.forename: Richard
authors.initials: R
authors.lastname: Kaplan
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D015331:Cohort Studies; D057915:Drug Substitution; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use*; D011320:Primary Health Care; D012189:Retrospective Studies; D012307:Risk Factors; D013019:South Africa; D000068698:Tenofovir
chemical_list: D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine