title: Outcomes of second-line combination antiretroviral therapy for HIV-infected patients: a cohort study from Rio de Janeiro, Brazil.
abstract: BACKGROUND
  World-wide, the notable expansion of HIV/AIDS treatment programs in resource-limited settings has lead to an increasing number of patients in need of second-line cART. To adequately address and prepare for this scenario, critical assessments of the outcomes of second-line cART are particularly relevant in settings where monitoring strategies may be inadequate. We evaluated virologic outcomes of second-line combination antiretroviral therapy (cART) among HIV-infected individuals from Brazil.
  
  
  METHODS
  This study was conducted at the Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, at Rio de Janeiro, Brazio. For this study we included all patients who started first-line and second-line cART between 2000 and 2013. Second-line cART required a switch in the anchor drug of first-line cART. We evaluated time from second-line start to virologic failure and factors associated with increased risk of failure using multivariable Cox proportional hazards regression models.
  
  
  RESULTS
  Among the 1,311 patients who started first-line cART a total of 386 patients (29.5%) initiated second-line cART, out of which 35.0% and 60.6% switched from their first-line to their second-line cART when their HIV RNA was undetectable and after documented virologic failure, respectively. At second line cART initiation, median age was 38 years [interquartile range (IQR): 31-45years]. Median CD4 count was significantly different for patients starting second-line cART undetectable [412 cells/mm3 (IQR: 240-617)] compared to those starting second-line cART after documented virologic failure [230 cells/mm3 (IQR: 118-322.5)] (p < 0.01). Median time from second-line cART initiation to failure was also significantly different for patients starting second-line cART undetectable compared to those who with documented virologic failure (log-rank test p < 0.01). Multivariable Cox models showed that younger age, lower education, and HIV RNA level were independently associated with an increased hazard of second-line failure among those with documented virologic failure at start of second-line cART.
  
  
  CONCLUSIONS
  We have shown that in a middle-income country with universal access to cART, having a detectable HIV RNA at the start of second-line cART as well as younger age and lower education negatively impact second-line outcomes. Our findings could guide HIV treatment efforts as to which strategies would help maximize the durability of these regimens.
authors.forename: Sandra W
authors.initials: SW
authors.lastname: Cardoso
authors.forename: Paula M
authors.initials: PM
authors.lastname: Luz
authors.forename: Luciane
authors.initials: L
authors.lastname: Velasque
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Torres
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Tavares
authors.forename: Sayonara R
authors.initials: SR
authors.lastname: Ribeiro
authors.forename: Ronaldo I
authors.initials: RI
authors.lastname: Moreira
authors.forename: Valdilea G
authors.initials: VG
authors.lastname: Veloso
authors.forename: Richard D
authors.initials: RD
authors.lastname: Moore
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
mesh_terms: D000328:Adult; D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001938:Brazil; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D016208:Databases, Factual; D004522:Educational Status; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors