title: Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.
abstract: BACKGROUND
  In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia.
  
  
  METHODS
  Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models.
  
  
  RESULTS
  A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1-26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79).
  
  
  CONCLUSIONS
  In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.forename: Hannock
authors.initials: H
authors.lastname: Tweya
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Paula
authors.initials: P
authors.lastname: Braitstein
authors.forename: Mauro
authors.initials: M
authors.lastname: Schecter
authors.forename: Martin W G
authors.initials: MW
authors.lastname: Brinkhof
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.forename: Suely
authors.initials: S
authors.lastname: Tuboi
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sprinz
authors.forename: Mar
authors.initials: M
authors.lastname: Pujades-Rodriguez
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: Denis
authors.initials: D
authors.lastname: Nash
authors.forename: Andreas
authors.initials: A
authors.lastname: Jahn
authors.forename: Patrick
authors.initials: P
authors.lastname: MacPhail
authors.forename: Ruedi
authors.initials: R
authors.lastname: Lüthy
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D018791:CD4 Lymphocyte Count; D003906:Developing Countries; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008507:Medically Underserved Area; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors