Trial Design

Dolutegravir-based regimens were studied in a Phase 3, treatment-experienced, INSTI-naïve trial1-3

  • Baseline characteristics: Median age was 43 years; 68% of patients were male, 42% were of African American/African heritage, 50% were white, 20% had HIV-1 RNA >100,000 copies/mL, 72% had CD4+T-cell counts <350 cells/mm3, 16% had hepatitis B and/or C virus co-infection, and 46% were CDC Class C (AIDS)
  • Primary endpoint: Proportion of patients with HIV-1 RNA <50 copies/mL at Week 48 (FDA snapshot analysis with 12% noninferiority margin with prespecified tests for superiority)
  • Baseline resistance prior to ART: 100% of patients had at least 2-class resistance and 49% were resistant to 3 classes

*BR was investigator selected and consisted of up to 2 agents including at least 1 fully active agent. Most common BRs: darunavir/r + TDF, lopinavir/r + TDF, darunavir/r + etravirine, lopinavir/r, atazanavir/r + TDF, darunavir/r + maraviroc.

Four patients were excluded from the efficacy and safety analyses: 3 from the arm receiving TIVICAY and 1 from the raltegravir arm due to good clinical practices noncompliance at one site.

INSTI=integrase strand transfer inhibitor; BR=background regimen; CDC=Centers for Disease Control and Prevention; ART=antiretroviral therapy; r=ritonavir; TDF=tenofovir.

Virologic Response

Statistically superior virologic response with dolutegravir at 48 weeks in SAILING (snapshot analysis: proportion of patients with HIV-1 RNA <50 copies/mL)2

Statistically superior difference:
  • Treatment difference (7.4% [95% CI; 0.7%, 14.2%]) was primarily driven by the rates of virologic nonresponse (20% for the regimens with TIVICAY vs 28% for the raltegravir regimens)1

Resistance Results

High barrier to resistance with dolutegravir is supported by 48-week results in SAILING2

  • No patients receiving dolutegravir had decreases in susceptibility (>2-fold) to dolutegravir in the resistance analysis data set (n=28 with confirmed PDVF at last visit through Week 48 and having resistance data)


Number of patients with treatment-emergent INSTI substitutions based on the resistance analysis data set through 48 weeks3

PDVF was defined as either virologic nonresponse (a decrease in plasma HIV-1 RNA <1 log10 copies/mL by Week 16, with subsequent confirmation, unless plasma HIV-1 RNA was <400 copies/mL; or confirmed plasma HIV-1 RNA 400 copies/mL on or after Week 24) or virologic rebound (confirmed rebound in plasma HIV-1 RNA to 400 copies/mL after prior confirmed suppression to <400 copies/mL, or confirmed plasma HIV-1 RNA >1 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 RNA value 400 copies/mL).

§At virologic failure, additional treatment-emergent INSTI-resistance substitutions were T97A and E138A/T, and a 148-fold reduction in susceptibility was observed.

PDVF=protocol-defined virologic failure.

Discontinuations Due to AEs

Proportion of patients who discontinued due to adverse events in treatment-experienced, INSTI-naïve trial2

AEs=adverse events.

Adverse Drug Reactions

SAILING—Grades 2 to 4 treatment-emergent adverse drug reactions (≥2% frequency) through 48 weeks

  • The only treatment-emergent adverse drug reaction of moderate to severe intensity with at least 2% frequency in either treatment group was diarrhea, 2% (6 of 354) in patients receiving TIVICAY 50 mg once daily + BR* and 1% (5 of 361) in patients receiving raltegravir 400 mg twice daily + BR*

Please see full Prescribing Information for TIVICAY.

References

  1. Cahn P, Pozniak AL, Mingrone H, et al; on behalf of the extended SAILING Study Team. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700-708.
  2. Data on file. ViiV Healthcare group of companies. Research Triangle Park, NC.