title: Long-term safety from the raltegravir clinical development program.
abstract: BACKGROUND
  Raltegravir has demonstrated potent and durable efficacy and a favorable safety profile in 3 phase III studies in treatment-naïve and treatment-experienced patients with HIV-1 infection. This manuscript provides a review of the raltegravir safety profile using data from these and other studies in the clinical development program.
  
  
  METHODS
  Comprehensive 96-week safety data from STARTMRK (raltegravir versus efavirenz, each with tenofovir/emtricitabine) and BENCHMRK (raltegravir versus placebo, each with optimized background therapy) are summarized. A cumulative meta-analysis of raltegravir 400 mg bid was conducted across the entire development program.
  
  
  RESULTS
  In STARTMRK, drug-related adverse events (AEs) occurred less frequently with raltegravir than efavirenz. In BENCHMRK, the most common drug-related AEs occurred at generally similar frequencies in both groups. Drug-related serious AEs were uncommon. Rash was observed in raltegravir-treated patients at a higher frequency than placebo but a lower frequency than efavirenz. Depression and immune reconstitution inflammatory syndrome occurred at similar rates for raltegravir and comparators. Isolated elevations of creatine kinase were more common with raltegravir than placebo but occurred without clinical manifestations. The frequency of aminotransferase elevations was greater in patients with viral hepatitis co-infection, but similar in the raltegravir and comparator groups. The relative risk (95% CI) of cancer was 0.75 (0.30, 1.91) indicating no difference between raltegravir and comparator. Overall trends in the cumulative meta-analysis were similar to those observed in the phase III studies.
  
  
  CONCLUSIONS
  Long-term data from the phase III clinical trials demonstrate that raltegravir was generally well-tolerated in both treatment-naïve and treatment-experienced patients with HIV infection.
authors.affiliation: Hedy Teppler, MD, Merck Research Laboratories, PO Box 1000, UG3D-56, North Wales, PA 19454-1099, USA. hedy_teppler@merck.com
authors.forename: Hedy
authors.initials: H
authors.lastname: Teppler
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Brown
authors.forename: Randi Y
authors.initials: RY
authors.lastname: Leavitt
authors.forename: Peter
authors.initials: P
authors.lastname: Sklar
authors.forename: Hong
authors.initials: H
authors.lastname: Wan
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Fabio
authors.initials: F
authors.lastname: Lievano
authors.forename: Heidi P
authors.initials: HP
authors.lastname: Lehman
authors.forename: T Christopher
authors.initials: TC
authors.lastname: Mast
authors.forename: Bach-Yen T
authors.initials: BY
authors.lastname: Nguyen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects*; D000068898:Raltegravir Potassium; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium