Observational Safety Data Analysis from Routine Follow-up in the EuroSIDA Study of Patients Treated with Raltegravir in a Five-Year Post Authorization Period (MK-0518-058)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Retrospective analysis of prospective cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (J05AR) Antivirals for treatment of HIV infections, combinations

  (J05AX08) raltegravir

Population studied

• Short description of the study population:
  All HIV-infected patients who are 16 years or older and report initiating treatment with raltegravir in the study cohort during the analysis period from 93 clinical centers in 31 European countries, Argentina and Israel.; ; Patients were included in the RAL patient cohort who:; • started RAL for the first time on or after the 21 December 2007 (RAL authorisation date in the European Union).; • had at least 1 month’s prospective follow-up in this cohort.; • had a CD4 count and a viral load measured within 6 months prior to the start date of RAL.; ; Patients were included in the historical comparison cohort who:; • started a new antiretroviral drug as part of a cART regimen on or after the 1 January 2006 and before 21 December 2007. The patient must have had no previous exposure to the new drug, including as part of a different co-formulation, e.g. if zidovudine (ZDV) had been previously received as part of Combivir and the patient started Trizivir, ZDV would not be counted as a new drug.; • had at least 1 month’s prospective follow-up in this cohort.; • had a CD4 count and a viral load measured within 6 months prior to the start date of the new drug.; ; Patients were included in the concurrent cohort not taking RAL who:; • started a new antiretroviral drug other than RAL as part of a cART regimen on or after the 21 December 2007. The patient must have had no previous exposure; to the new drug, including as part of a different co-formulation.; • had at least 1 month’s prospective follow-up in this cohort.; • had a CD4 count and a viral load measured within 6 months prior to the start date of the new drug
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Special population of interest:
  Immunocompromised
• Estimated number of subjects:
  6617

Study design details

• Main study objective:
  The overall objective of this analysis is to investigate the incidence of clinically important medical events following treatment with raltegravir. Incidence rates of medical events and all cause mortality will be determined for raltegravir recipients over the duration of raltegravir exposure and among both a historical and concurrent comparison group.
• Outcomes:
  1. Incidence of malignancy in patients treated with raltegravir2. Incidence of clinically important hepatic events in patients treated with raltegravir3. Incidence of lipodystrophy in patients treated with raltegravir4. Incidence of all-cause mortality in patients treated with raltegravir, 1. Incidence of malignancy in a post-licensure concurrent comparison cohort2. Incidence of clinically important hepatic events in a post-licensure concurrent comparison cohort3. Incidence of lipodystrophy in a post-licensure concurrent comparison cohort4. Incidence of all-cause mortality in a post-licensure concurrent comparison cohort
• Data analysis plan:
  Incidence rates, and 95% confidence intervals of each pre-specified medical events were tabulated. Multivariate regression was used to compare the incidence rates ofraltegravir versus the historical comparison group. Rate ratios (RR) of adverse events were calculated, and regression models that incorporate propensity scores were used to adjust simultaneously for the potentially confounding effects of selected variables and comparison group characteristics using Poisson regression. Descriptive statistics will be used to describe the heterogeneity in the treatment experience and treatment failure history of raltegravir patients at initiation of therapy.