PMID- 25350958
OWN - NLM
STAT- MEDLINE
DCOM- 20141230
LR  - 20201209
IS  - 1528-4336 (Print)
IS  - 1528-4336 (Linking)
VI  - 15
IP  - 5
DP  - 2014 Sep-Oct
TI  - Dolutegravir: clinical and laboratory safety in integrase inhibitor-naive 
      patients.
PG  - 199-208
LID - 10.1310/hct1505-199 [doi]
AB  - 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.
FAU - Curtis, L
AU  - Curtis L
AD  - GlaxoSmithKline, Stockley Park, UK.
FAU - Nichols, G
AU  - Nichols G
AD  - GlaxoSmithKline, Research Triangle Park, NC, USA.
FAU - Stainsby, C
AU  - Stainsby C
AD  - GlaxoSmithKline, Stockley Park, UK.
FAU - Lim, J
AU  - Lim J
AD  - GlaxoSmithKline, Stockley Park, UK.
FAU - Aylott, A
AU  - Aylott A
AD  - GlaxoSmithKline, Stockley Park, UK.
FAU - Wynne, B
AU  - Wynne B
AD  - GlaxoSmithKline, Philadelphia, PA, USA.
FAU - Clark, A
AU  - Clark A
AD  - ViiV Healthcare, Brentford, UK.
FAU - Bloch, M
AU  - Bloch M
AD  - Holdsworth House Medical Practice, Sydney, Australia.
FAU - Maechler, G
AU  - Maechler G
AD  - ViiV Healthcare, Brentford, UK.
FAU - Martin-Carpenter, L
AU  - Martin-Carpenter L
AD  - ViiV Healthcare, Research Triangle Park, NC, USA.
FAU - Raffi, F
AU  - Raffi F
AD  - Infectious and Tropical Diseases Department, Nantes University Hospital, Nantes, 
      France.
FAU - Min, S
AU  - Min S
AD  - GlaxoSmithKline, Research Triangle Park, NC, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - HIV Clin Trials
JT  - HIV clinical trials
JID - 100936377
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (Lipids)
RN  - 0 (Oxazines)
RN  - 0 (Piperazines)
RN  - 0 (Pyridones)
RN  - DKO1W9H7M1 (dolutegravir)
RN  - EC 2.7.3.2 (Creatine Kinase)
SB  - IM
MH  - Anti-HIV Agents/*adverse effects/*therapeutic use
MH  - Chemical and Drug Induced Liver Injury/blood
MH  - Creatine Kinase/blood
MH  - HIV Infections/*drug therapy
MH  - Heterocyclic Compounds, 3-Ring/*adverse effects/*therapeutic use
MH  - Humans
MH  - Lipids/blood
MH  - Oxazines
MH  - Piperazines
MH  - Psychoses, Substance-Induced
MH  - Pyridones
MH  - Systemic Inflammatory Response Syndrome/chemically induced
OTO - NOTNLM
OT  - HIV-1
OT  - dolutegravir
OT  - integrase inhibitor
OT  - safety
EDAT- 2014/10/29 06:00
MHDA- 2014/12/31 06:00
CRDT- 2014/10/29 06:00
PHST- 2014/10/29 06:00 [entrez]
PHST- 2014/10/29 06:00 [pubmed]
PHST- 2014/12/31 06:00 [medline]
AID - 088385NV8428X738 [pii]
AID - 10.1310/hct1505-199 [doi]
PST - ppublish
SO  - HIV Clin Trials. 2014 Sep-Oct;15(5):199-208. doi: 10.1310/hct1505-199.