Dolutegravir-based regimens were studied in a Phase 3, treatment-experienced, INSTI-naïve trial1,2
- 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 disoproxil fumarate.
Statistically superior virologic response with dolutegravir at 48 weeks in SAILING (snapshot analysis: proportion of patients with HIV-1 RNA <50 copies/mL)1
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
High barrier to resistance with dolutegravir is supported by 48-week results in SAILING2
Number of patients with treatment-emergent INSTI substitutions based on the resistance analysis data set through 48 weeks2
Discontinuations Due to AEs
Proportion of patients who discontinued due to adverse events in a treatment-experienced, INSTI-naïve trial2
Adverse Drug Reactions (ADRs)
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*
Indications and Usage
TIVICAY is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with:
- other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 30 kg
- rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable antiretroviral regimen for ≥6 months with no history of treatment failure or known substitutions associated with resistance to either antiretroviral agent
Important Safety Information
- Do not use TIVICAY in patients with previous hypersensitivity reaction to dolutegravir
- Do not use TIVICAY in patients receiving dofetilide
WARNINGS AND PRECAUTIONS
- Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
- Discontinue TIVICAY immediately if signs or symptoms of hypersensitivity reaction develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated
- Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure) in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors
- Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY. In some cases the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
- Monitoring for hepatotoxicity is recommended
- Avoid use of TIVICAY at the time of conception through the first trimester due to the risk of neural tube defects
- Perform pregnancy testing before use of TIVICAY and advise that consistent use of effective contraception is recommended while using TIVICAY in adolescents and adults of childbearing potential
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:
The concomitant use of TIVICAY and other drugs may result in known or potentially significant drug interactions (see Contraindications or Drug Interactions)
Immune Reconstitution Syndrome,
including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of TIVICAY.
The most common adverse reactions (incidence ≥2%, Grades 2-4) in treatment-naïve adults receiving TIVICAY in a combination regimen were insomnia (3%), headache (2%), and fatigue (2%).
- Coadministration of TIVICAY with drugs that induce or inhibit UGT1A1 and/or CYP3A may affect plasma concentrations
- Administer TIVICAY 2 hours before or 6 hours after taking antacids, polyvalent cation-containing products or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, oral calcium and iron supplements (including multivitamins containing calcium or iron) can be taken with TIVICAY if coadministered with a meal
- Consult the full Prescribing Information for TIVICAY for more information on potentially significant drug interactions, including clinical comments
USE IN SPECIFIC POPULATIONS
There are insufficient human data on the use of TIVICAY during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Avoid use of TIVICAY at the time of conception through the first trimester of pregnancy. If planning a pregnancy or if pregnancy is confirmed while taking dolutegravir during the first trimester, if possible, switch to an alternative regimen
Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
Females and Males of Reproductive Potential:
Perform pregnancy testing before initiation of TIVICAY. Advise adolescents and adults of childbearing potential to consistently use effective contraception while taking TIVICAY
- 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.
- Data on file. ViiV Healthcare group of companies. Research Triangle Park, NC.