title: Rate and determinants of treatment response to different antiretroviral combination strategies in subjects presenting at HIV-1 diagnosis with advanced disease.
abstract: BACKGROUND
  The optimal therapeutic strategies for patients presenting with advanced disease at HIV-1 diagnosis are as yet incompletely defined.
  
  
  METHODS
  All patients presenting at two outpatient clinics in 2000-2009 with an AIDS-defining clinical condition or a CD4+ T cell count < 200/μL at HIV-1 diagnosis were analyzed for the presence of combined immunovirological response, defined by the concomitant presence of an absolute number of CD4+ T cells > 200 cells/μL and a plasma HIV-1 RNA copy number < 50/mL after 12 months of HAART.
  
  
  RESULTS
  Among 102 evaluable patients, first-line regimens were protease inhibitors [PI]-based in 78 cases (77%) and efavirenz-based in 24 cases (23%). The overall response rate was 65% (95% CI: 55-74), with no differences by gender, age, nationality, route of transmission, hepatitis virus coinfections, presence of AIDS-defining clinical events, baseline HIV-1 viral load, or type of regimen (response rates with PI-based and efavirenz-based therapy: 63% and 71%, respectively, p = 0.474). Response rate was significantly better with higher baseline CD4+ T cell counts (78% with CD4+ ≥ 100/μL, compared to 50% with CD4+ < 100/μL; odds ratio: 3.5; 95% CI: 1.49-8.23, p = 0.003). Median time on first-line antiretroviral therapy was 24 months (interquartile range: 12-48). Switch to a second line treatment occurred in 57% of patients, mainly for simplification (57%), and was significantly more common with PI-based regimens [adjusted hazard ratios (AHR) with respect to efavirenz-based regimens: 3.88 for unboosted PIs (95% CI: 1.40-10.7, p = 0.009) and 4.21 for ritonavir-boosted PI (95% CI 1.7-10.4, p = 0.002)] and in older subjects (≥ 50 years) (AHR: 1.83; 95% CI: 1.02-3.31, p = 0.044). Overall mortality was low (3% after a median follow up of 48 months).
  
  
  CONCLUSIONS
  Our data indicate that a favorable immunovirological response is possible in the majority of naive patients presenting at HIV-1 diagnosis with AIDS or low CD4+ T cell counts, and confirm that starting HAART with a more compromised immune system may be associated with a delayed and sometimes partial immune recovery. Simpler regimens may be preferable in this particular population.
authors.affiliation: Dpt, of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Esposito
authors.forename: Marco
authors.initials: M
authors.lastname: Floridia
authors.forename: Gabriella
authors.initials: G
authors.lastname: d'Ettorre
authors.forename: Daniele
authors.initials: D
authors.lastname: Pastori
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fantauzzi
authors.forename: Paola
authors.initials: P
authors.lastname: Massetti
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ceccarelli
authors.forename: Camilla
authors.initials: C
authors.lastname: Ajassa
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
mesh_terms: D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz; D019438:Ritonavir