Dolutegravir efficacy at 48 weeks in key subgroups of treatment-naive HIV-infected individuals in three randomized trials.
OBJECTIVE
Dolutegravir (DTG) has been studied in three trials in HIV treatment-naive participants, showing noninferiority compared with raltegravir (RAL), and superiority compared with efavirenz and ritonavir-boosted darunavir. We explored factors that predicted treatment success, the consistency of observed treatment differences across subgroups and the impact of NRTI backbone on treatment outcome.


METHODS
Retrospective exploratory analyses of data from three large, randomized, international comparative trials: SPRING-2, SINGLE, and FLAMINGO.


METHODS
We examined the efficacy of DTG in HIV-infected participants with respect to relevant demographic and HIV-1-related baseline characteristics using the primary efficacy endpoint from the studies (FDA snapshot) and secondary endpoints that examine specific elements of treatment response. Regression models were used to analyze pooled data from all three studies.


RESULTS
Snapshot response was affected by age, hepatitis co-infection, HIV risk factor, baseline CD4⁺ cell count, and HIV-1 RNA and by third agent. Differences between DTG and other third agents were generally consistent across these subgroups. There was no evidence of a difference in snapshot response between abacavir/lamivudine (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) overall [ABC/3TC 86%, TDF/FTC 85%, difference 1.1%, confidence interval (CI) -1.8, 4.0 percentage points, P = 0.61] or at high viral loads (difference -2.5, 95% CI -8.9, 3.8 percentage points, P = 0.42).


CONCLUSIONS
DTG is a once-daily, unboosted integrase inhibitor that is effective in combination with either ABC/3TC or TDF/FTC for first-line antiretroviral therapy in HIV-positive individuals with a variety of baseline characteristics.
aUniversity of Nantes, Nantes, France bSunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada cCentral Texas Clinical Research, Austin, Texas, USA dEPIMED/Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany eFundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain fGlaxoSmithKline, Research Triangle Park, North Carolina, USA gGlaxoSmithKline, Mississauga, Ontario, Canada hGlaxoSmithKline, Stockley Park, Uxbridge iViiV Healthcare, Brentford, UK jUniversity of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA kUniversity Health Network, University of Toronto, Toronto, Ontario, Canada.
François
F
Raffi
Anita
A
Rachlis
Cynthia
C
Brinson
Keikawus
K
Arasteh
Miguel
M
Górgolas
Clare
C
Brennan
Keith
K
Pappa
Steve
S
Almond
Catherine
C
Granier
W Garrett
WG
Nichols
Robert Liam
RL
Cuffe
Joseph
J
Eron
Sharon
S
Walmsley
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D017326:Clinical Trials, Phase III as Topic; D060085:Coinfection; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D000099226:Dolutegravir; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D019259:Lamivudine; D063065:Organophosphonates; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019438:Ritonavir; D000068698:Tenofovir; D000099226:Dolutegravir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir