title: Dolutegravir: clinical and laboratory safety in integrase inhibitor-naive patients.
abstract: BACKGROUND
  The efficacy of dolutegravir (DTG) has been demonstrated in 5 randomized studies in integrase inhibitor (INI)-naive adult populations. To date, a detailed safety review of DTG has not been provided in the literature.
  
  
  OBJECTIVE
  To describe the safety and tolerability profile of DTG in adults based on 5 randomized, controlled trials and comparison with drugs in 3 major antiretroviral (ARV) classes.
  
  
  METHODS
  Safety data from phase IIb/III/IIIb trials in ART-naive and ART-experienced, INI-naive adults were integrated.
  
  
  RESULTS
  In 4 ART-naive (SPRING-1, SPRING-2, SINGLE, FLAMINGO) and 1 ART-experienced, INI-naive study (SAILING), 1,579 individuals received a DTG-containing regimen. The proportion of individuals from DTG treatment arms who withdrew due to adverse events (AEs) was low (≤2%) compared to raltegravir (RAL; 2% SPRING-2, 4% SAILING), efavirenz (EFV)-containing comparator arm (10% SINGLE), and darunavir + ritonavir (DRV/r; 4% FLAMINGO). The most frequently observed AEs (diarrhea, nausea, headache), typically grade 1 or 2 in severity, did not lead to study discontinuation. Psychiatric and nervous system disorders with DTG were comparable to RAL- and DRV/r-containing regimens and favorable to EFV-containing regimens. In hepatitis B and/or C coinfected ART-naive individuals, the incidence of transaminase elevations was lower with DTG versus RAL and EFV comparators, but was similar to DRV/r. In SAILING, transaminase elevations were more commonly observed with DTG, particularly in the setting of inadequate hepatitis B therapy or immune reconstitution. On DTG treatment, mild creatinine elevations occurred and stabilized early. Few cases of hypersensitivity reaction and/or severe rash were seen. Rates of these events were comparable to or lower than with RAL-, EFV-, and DRV/r-containing regimens.
  
  
  CONCLUSIONS
  The safety profile for DTG 50 mg once daily in INI-naive individuals was comparable to RAL- and DRV/r-containing regimens and generally favorable compared with EFV-containing regimens.
authors.affiliation: GlaxoSmithKline, Stockley Park, UK.
authors.forename: L
authors.initials: L
authors.lastname: Curtis
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: G
authors.initials: G
authors.lastname: Nichols
authors.affiliation: GlaxoSmithKline, Stockley Park, UK.
authors.forename: C
authors.initials: C
authors.lastname: Stainsby
authors.affiliation: GlaxoSmithKline, Stockley Park, UK.
authors.forename: J
authors.initials: J
authors.lastname: Lim
authors.affiliation: GlaxoSmithKline, Stockley Park, UK.
authors.forename: A
authors.initials: A
authors.lastname: Aylott
authors.affiliation: GlaxoSmithKline, Philadelphia, PA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Wynne
authors.affiliation: ViiV Healthcare, Brentford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Clark
authors.affiliation: Holdsworth House Medical Practice, Sydney, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Bloch
authors.affiliation: ViiV Healthcare, Brentford, UK.
authors.forename: G
authors.initials: G
authors.lastname: Maechler
authors.affiliation: ViiV Healthcare, Research Triangle Park, NC, USA.
authors.forename: L
authors.initials: L
authors.lastname: Martin-Carpenter
authors.affiliation: Infectious and Tropical Diseases Department, Nantes University Hospital, Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Raffi
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Min
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000097:blood; D010078:Oxazines; D010879:Piperazines; D011605:Psychoses, Substance-Induced; D011728:Pyridones; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced; D000099226:Dolutegravir
chemical_list: D019380:Anti-HIV Agents; D003402:Creatine Kinase; D006575:Heterocyclic Compounds, 3-Ring; D008055:Lipids; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000099226:Dolutegravir
keywords: HIV-1; dolutegravir; integrase inhibitor; safety