For HIV-1. See Full Indication.

EFFICACY AND RESISTANCE

SAILING: DOLUTEGRAVIR-BASED REGIMENS PUT TO THE TEST IN PATIENTS WITH PRIOR ART RESISTANCE1

A randomized, double-blind, active-control, noninferiority trial in 719 treatment-experienced, INSTI-naïve adult (≥18 years) patients with HIV-1Eligible participants had to have 2 consecutive plasma HIV-1 RNA assessments of ≥400 copies/mL (unless >1000 copies/mL at screening).

Baseline characteristics
Median age was 43 years; 68% of patients were male, 42% were of African American/African heritage, 49% 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 coinfection, 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)

Virologic Response

When put to the test in patients with prior ART resistance, DTG-based regimens showed a statistically superior difference in virologic response at Week 48 (ITT–E; primary endpoint)1,2†

VIROLOGIC RESPONSE IN PATIENTS WITH HIGH BASELINE VIRAL LOAD1

SUBGROUP ANALYSIS

Virologic response (HIV-1 RNA <50 copies/mL) stratified by baseline viral load

VIROLOGIC RESPONSE IN PATIENTS WITH LOW BASELINE VIRAL LOAD1

SUBGROUP ANALYSIS

Virologic response (HIV-1 RNA <50 copies/mL) stratified by baseline viral load

Resistance Results

High barrier to resistance with dolutegravir is supported by 48-week results in SAILING1

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 weeks2

*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.
Prespecified secondary endpoint; ITT-E population.
§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).
||One subject isolate had pre-existing raltegravir resistance substitutions E138A, G140S, and Q148H at baseline and had additional emergent INSTI-resistance substitutions T97A and E138A/T with a corresponding 148-fold reduction in dolutegravir susceptibility at failure.

ART=antiretroviral therapy; INSTI=integrase strand transfer inhibitor; BR=background regimen; FDA=Food and Drug Administration; CI=confidence interval; PDVF=protocol defined virologic failure; DTG=dolutegravir; RAL=raltegravir; TDF=tenofovir disoproxil fumarate; ITT-E=intent-to-treat--exposed.

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.

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