title: Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis.
abstract: BACKGROUND
  Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy.
  
  
  METHODS
  We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately.
  
  
  RESULTS
  A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined.
  
  
  CONCLUSIONS
  Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.
authors.affiliation: Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases L, Spallanzani, IRCCS, Via Portuense 292, 00149, Rome, Italy. enrico.girardi@inmi.it
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Paola
authors.initials: P
authors.lastname: Scognamiglio
authors.forename: Claudio
authors.initials: C
authors.lastname: Angeletti
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
authors.forename: Dora
authors.initials: D
authors.lastname: Buonfrate
authors.forename: Massimo
authors.initials: M
authors.lastname: Arlotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mazzarello
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000592:standards / Q000600:supply & distribution*; D002986:Clinical Trials as Topic / Q000941:ethics / Q000592:standards; D015897:Comorbidity; D057176:Compassionate Use Trials / Q000941:ethics / Q000592:standards; D015507:Drugs, Investigational / Q000592:standards / Q000600:supply & distribution*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006297:Health Services Accessibility / Q000941:ethics / Q000592:standards*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008107:Liver Diseases / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D055361:Multilevel Analysis; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015507:Drugs, Investigational