title: The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring.
abstract: OBJECTIVE
  We examined the effect of switching to second-line antiretroviral therapy (ART) on mortality in patients who experienced immunological failure in ART programmes without access to routine viral load monitoring in sub-Saharan Africa.
  
  
  METHODS
  Collaborative analysis of two ART programmes in Lusaka, Zambia and Lilongwe, Malawi.
  
  
  METHODS
  We included all adult patients experiencing immunological failure based on WHO criteria. We used Cox proportional hazards models weighted by the inverse probability of switching to compare mortality between patients who switched and patients who did not; and between patients who switched immediately and patients who switched later. Results are expressed as hazard ratios with 95% credible intervals (95% CI).
  
  
  RESULTS
  Among 2411 patients with immunological failure 324 patients (13.4%) switched to second-line ART during 3932 person-years of follow-up. The median CD4 cell count at start of ART and failure was lower in patients who switched compared to patients who did not: 80 versus 155 cells/μl (P < 0.001) and 77 versus 146 cells/μl (P < 0.001), respectively. Adjusting for baseline and time-dependent confounders, mortality was lower among patients who switched compared to patients remaining on failing first-line ART: hazard ratio 0.25 (95% CI 0.09-0.72). Mortality was also lower among patients who remained on failing first-line ART for shorter periods: hazard ratio 0.70 (95% CI 0.44-1.09) per 6 months shorter exposure.
  
  
  CONCLUSIONS
  In ART programmes switching patients to second-line regimens based on WHO immunological failure criteria appears to reduce mortality, with the greatest benefit in patients switching immediately after immunological failure is diagnosed.
authors.affiliation: Division of International and Environmental Health, Institute of Social and Preventive Medicine, University of Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gsponer
authors.forename: Maya
authors.initials: M
authors.lastname: Petersen
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Sam
authors.initials: S
authors.lastname: Phiri
authors.forename: Marloes H
authors.initials: MH
authors.lastname: Maathuis
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Patrick
authors.initials: P
authors.lastname: Musondad
authors.forename: Hannock
authors.initials: H
authors.lastname: Tweya
authors.forename: Karin
authors.initials: K
authors.lastname: Peter
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Chi
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D015497:HIV-1; D006297:Health Services Accessibility; D006801:Humans; D008295:Malawi / Q000453:epidemiology; D008297:Male; D016016:Proportional Hazards Models; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects; D015024:Zambia / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents
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