title: Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study.
abstract: BACKGROUND
  Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil.
  
  
  METHODS
  Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load<50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression.
  
  
  RESULTS
  Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI=69.7-86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI=103.4-159.6). In multiple logistic regression analysis, higher baseline viral load (RR=1.04 per 10,000 copies/mL increase; 95% CI=1.01-1.09) and higher number of darunavir resistance-associated mutations (RR=1.23 per each; 95% CI=0.95-1.48) were independently associated with virologic failure.
  
  
  CONCLUSIONS
  Virologic suppression is a realistic endpoint for most treatment-experienced patients who begin a darunavir-based therapy outside the controlled conditions of a randomized trial, at routine care settings.
authors.affiliation: Postgraduate Program on Health Sciences: Infectious Diseases and Tropical Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: karinamotaribeiro@gmail.com.
authors.forename: Karina Mota
authors.initials: KM
authors.lastname: Ribeiro
authors.affiliation: School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Fernando Martin
authors.initials: FM
authors.lastname: Biscione
authors.affiliation: Postgraduate Program on Health Sciences: Infectious Diseases and Tropical Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Mateus Rodrigues
authors.initials: MR
authors.lastname: Westin
authors.affiliation: School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Danielle Pessoa
authors.initials: DP
authors.lastname: Machado
authors.affiliation: Postgraduate Program on Health Sciences: Infectious Diseases and Tropical Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Dirceu Bartolomeu
authors.initials: DB
authors.lastname: Greco
authors.affiliation: Postgraduate Program on Health Sciences: Infectious Diseases and Tropical Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Unaí
authors.initials: U
authors.lastname: Tupinambás
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001938:Brazil; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016879:Salvage Therapy; D013449:Sulfonamides / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D013449:Sulfonamides; D000069454:Darunavir
keywords: Genotyping techniques; HIV-1; Highly active antiretroviral therapy; Multiple viral drug resistance; Salvage therapy
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