title: Changes in second-line regimen durability and continuity of care in relation to national ART guideline changes in South Africa.
abstract: Little is known about the impact of antiretroviral therapy (ART) guideline changes on the durability of second-line ART and continuity of care. This study examines predictors of early drug substitutions and treatment interruptions using a cohort analysis of HIV positive adults switched to second-line ART between January 2004 and September 2013 in Johannesburg, South Africa.
  
  
  
  The main outcomes were having a drug substitution or treatment interruption in the first 24 months on second-line ART. Kaplan Meiers analyses and Cox proportional hazards regression were used to identify predictors of drug substitutions and treatment interruptions.
  
  
  
  Of 3028 patients on second-line ART, 353 (11.7%) had a drug substitution (8.6 per 100PY, 95% CI: 7.8-9.6) and 260 (8.6%) had a treatment interruption (6.3 per 100PY, 95% CI: 5.6-7.1). While treatment interruptions decreased from 32.5 per 100PY for the 2004 cohort to 2.3 per 100PY for the 2013 cohort, the rates of drug substitutions steadily increased, peaking at an incidence of 26.7 per 100PY for the 2009 cohort and then decreased to 4.2 per 100PY in the 2011 cohort. Compared to the 2004 to 2008 cohorts, the hazard of early drug substitutions was highest among patients switched to AZT + ddI + LPVr in 2009 to 2010 (aHR 5.1, 95% CI: 3.4-7.1) but remained low over time among patients switched to TDF + 3TC/FTC + LPVr or AZT/ABC + 3TC + LPVr. The main common predictor of both treatment interruption and drug substitution was drug toxicity.
  
  
  
  Our results show a rapid transition between 2004 and 2010 ART guidelines and concurrent improvements in continuity of care among second-line ART patients. Drug toxicity reporting and monitoring systems need improvements to inform timely regimen changes and ensure that patients remain in care. However, reasons for drug substitutions should be closely monitored to ensure that patients do not run out of treatment options in the future.
authors.affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Dorina
authors.initials: D
authors.lastname: Onoya
authors.affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Department of Global Health, Boston University School of Public Health, Boston, MA, USA.|Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Alana T
authors.initials: AT
authors.lastname: Brennan
authors.affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Right to Care, Johannesburg, South Africa.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Berhanu
authors.affiliation: Right to Care, Johannesburg, South Africa.
authors.forename: Liudmyla
authors.initials: L
authors.lastname: van der Berg
authors.affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Thulasizwe
authors.initials: T
authors.lastname: Buthelezi
authors.affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Department of Global Health, Boston University School of Public Health, Boston, MA, USA.|Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fox
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D003266:Continuity of Patient Care; D057915:Drug Substitution; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D013019:South Africa
chemical_list: D019380:Anti-HIV Agents
keywords: HIV treatment; South Africa; antiretroviral therapy; drug substitution; second-line regimen; treatment durability; treatment interruption.