Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study

Hans Jürgen Stellbrink, Jacques Reynes, Adriano Lazzarin, Eugene Voronin, Federico Pulido, Franco Felizarta, Steve Almond, Marty St Clair, Nancy Flack, Sherene Min

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To evaluate the efficacy and safety/tolerability of dolutegravir (DTG, S/GSK1349572), a potent inhibitor of HIV integrase, through the full 96 weeks of the SPRING-1 study. DESIGN: ING112276 (SPRING-1) was a 96-week, randomized, partially blinded, phase IIb dose-ranging study. METHODS: Treatment-naive adults with HIV received DTG 10, 25, or 50  mg once daily or efavirenz (EFV) 600 mg once daily (control arm) combined with investigator-selected dual nucleos(t)ide reverse transcriptase inhibitor backbone regimen (tenofovir/emtricitabine or abacavir/lamivudine). The primary endpoint of the study was the proportion of participants with plasma HIV-1 RNA less than 50 copies/ml, based on time to loss of virologic response at 16 weeks (conducted for the purpose of phase III dose selection), with a planned analysis at 96 weeks. Safety and tolerability were also assessed. RESULTS: Of 208 participants randomized to treatment, 205 received study drug. At week 96, the proportion of participants achieving plasma HIV-1 RNA less than 50 copies/ ml was 79, 78, and 88% for DTG 10, 25, and 50 mg, respectively, compared with 72% for EFV. The median increase from baseline in CD4 cells was 338 cells/μl with DTG (all treatment groups combined) compared with 301 cells/μl with EFV (P = 0.155). No clinically significant dose-related trends in adverse events were observed, and fewer participants who received DTG withdrew because of adverse events (3%) compared with EFV (10%). CONCLUSION: Throughout the 96 weeks of the SPRING-1 study, DTG demonstrated sustained efficacy and favorable safety/tolerability in treatment-naive individuals with HIV-1.

Original languageEnglish
Pages (from-to)1771-1778
Number of pages8
JournalAIDS (London, England)
Volume27
Issue number11
DOIs
Publication statusPublished - Jul 17 2013

Keywords

  • antiretroviral agents
  • HIV integrase
  • HIV integrase inhibitors
  • HIV-1
  • reverse transcriptase inhibitors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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