title: Clinical and Virologic Outcomes After Changes in First Antiretroviral Regimen at 7 Sites in the Caribbean, Central and South America Network.
abstract: BACKGROUND
  HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications.
  
  
  METHODS
  HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2.
  
  
  RESULTS
  Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8).
  
  
  CONCLUSIONS
  Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.
authors.affiliation: *Fundación Arriarán/Facultad de Medicina, Universidad de Chile, Santiago, Chile;†Departments of Biostatistics and Medicine, Vanderbilt University, Nashville, TN;‡Fundación Huésped, Buenos Aires, Argentina;§Instituto de Pesquisa Clinica Evandro Chagas-Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;‖Le Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes, Port-au-Prince, Haiti;¶Instituto Hondureño de Seguridad Social and Hospital Escuela, Tegucigalpa, Honduras;#Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, México; and**Instituto de Medicina Tropical Alexander von Humboldt, Lima, Peru.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Wolff
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: Claudia
authors.initials: C
authors.lastname: Cortés
authors.forename: Peter
authors.initials: P
authors.lastname: Rebeiro
authors.forename: Carina
authors.initials: C
authors.lastname: Cesar
authors.forename: Sandra
authors.initials: S
authors.lastname: Wagner Cardoso
authors.forename: Jean W
authors.initials: JW
authors.lastname: Pape
authors.forename: Denis
authors.initials: D
authors.lastname: Padgett
authors.forename: Juan
authors.initials: J
authors.lastname: Sierra-Madero
authors.forename: Juan
authors.initials: J
authors.lastname: Echevarria
authors.forename: Catherine C
authors.initials: CC
authors.lastname: McGowan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D017691:Caribbean Region / Q000453:epidemiology; D002489:Central America / Q000453:epidemiology; D002985:Clinical Protocols; D015331:Cohort Studies; D057915:Drug Substitution / Q000706:statistics & numerical data; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D013020:South America / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents