D3

OUR TOMORROW STARTS WITH 2

MAKE THEIR FIRST HIV REGIMEN A 2-DRUG REGIMEN

D3

Explore the Clinical Data

GEMINI-1 and GEMINI-2:
2 Fully Powered Studies With More Than 700 Patients Each

2 identically designed, double-blind, treatment-naïve Phase III studies1:

  • Objective: demonstrate non-inferior efficacy of DTG 50 mg + 3TC 300 mg to
    DTG 50 mg + TDF/FTC 300 mg/200 mg
  • Primary endpoint: percent of patients with plasma HIV-1 RNA <50 copies/mL at Week 48 (by Snapshot algorithm)

 

RAMs=resistance-associated mutations.

Gemini_graph 1:1Baseline Randomisation DTG + TDF/FTC (n=717) DTG + 3TC (n=716) Week 48: Primary Endpoint GEMINI-1 and GEMINI-2 (pooled) • Treatment naïve • Viral load 1,000 copies/mL to 500,000 copies/mL • HBV negative • No major RAMs • ≥18 years old Week 96 >Week 144
Gemini_graph_Mobile 1:1Baseline Randomisation DTG + 3TC (n=716) DTG + TDF/FTC (n=717) Week 48: Primary Endpoint Week 96 Week 144 GEMINI-1 and GEMINI-2 (pooled) • Treatment naïve • Viral load 1,000 copies/mL to 500,000 copies/mL • HBV negative • No major RAMs • ≥18 years old

 

TIVICAY + Lamivudine: Powerful Efficacy in Treatment-Naïve Adults

DTG + 3TC Non-Inferior to a 3-Drug Regimen at Week 48

*Treatment-related discontinuation=failure population accounts for confirmed virological withdrawal, withdrawal due to lack of efficacy, withdrawal due to treatment-related adverse event, and participants who met protocol-defined stopping criteria.1

DTG + 3TC CD4+ T-cell count <200 Snapshot non-response (n=13): 1 confirmed virological withdrawal, 3 with viral load >50 copies/mL in window (2 of 3 re-suppressed),
2 discontinued due to adverse event (tuberculosis, Chagas disease), 2 protocol violations, 2 lost to follow-up, 1 withdrew consent, 1 withdrew to start hepatitis C treatment,
1 change in ART (incarcerated).1

DTG + TDF/FTC CD4+ T-cell count <200 Snapshot non-response (n=4):1 investigator discretion, 1 withdrew consent, 1 lost to follow-up, 1 viral load >50 copies/mL
(re-suppressed).1

ITT–E=intent-to-treat exposed.

 

In GEMINI-1 and GEMINI-2:
TIVICAY + Lamivudine—High Barrier to Resistance up to 48 Weeks

0

CASES OF RESISTANCE-ASSOCIATED MUTATIONS1

     
  Number of Patients
in Treatment Arm
Confirmed Virological
Withdrawal
Number of Patients
With Mutations
NRTI
Mutations
INI
Mutations
DTG + 3TC;
pooled, n (%)
716 6 (<1%) 0 0 0
DTG + TDF/FTC;
pooled, n (%)
717 4 (<1%) 0 0 0

 

Overall, Adverse Events Were Comparable Across Both Arms at 48 Weeks1

Fewer Drug-Related Adverse Events (AEs) with TIVICAY + lamivudine

 

   
  DTG + 3TC
(n=716; pooled),
n (%)
DTG + TDF/FTC
(n=717; pooled),
n (%)
Any AE 543 (76%) 579 (81%)
Drug-related AEs 126 (18%) 169 (24%)
Drug-related AEs, Grade 2 to Grade 4, ≥1% in either arm 42 (6%) 47 (7%)
Drug-related AEs, Grade 2 to Grade 4—Headache 8 (1%) 8 (1%)
AEs leading to withdrawal 15 (2%) 16 (2%)
Neuropsychiatric AEs leading to withdrawal 6 (<1%) 4 (<1%)
Any serious AEs* 50 (7%) 55 (8%)

*2 deaths (acute myocardial infarction, n=1; Burkitt's lymphoma, n=1) in GEMINI-2 study; both were in the DTG + 3TC group and were considered unrelated to the study drug regimen.1

Improvement in indicators of potential long term toxicities

  • Statistically significant change in renal and bone biomarkers from baseline favours DTG + 3TC vs DTG + TDF/FTC1
  • Improvements in TC/HDL ratio in both treatment arms1

 

RENAL

  • Statistically significant change in eGFR (cystatin C) favouring DTG + 3TC1
  • Statistically significant change in urine protein/creatinine, retinol-binding protein/creatinine and beta-2 microglobulin/creatinine ratios favouring DTG + 3TC1

 

STATISTICALLY SIGNIFICANT IMPROVEMENTS IN RENAL BIOMARKERS1

PLASMA/SERUM MARKERS (ITT-E POOLED ANALYSIS)1URINE MARKERS (ITT-E POOLED ANALYSIS)1 

Adapted from Cahn et al, 2018.1

The clinical significance of these values may vary in individual patients.

LIPIDS

  • TC/HDL ratio improved in both arms with a statistically significant greater reduction in the 
    DTG + TDF/FTC arm1

 

IMPROVEMENT IN TC/HDL RATIO IN BOTH TREATMENT ARMS1

SERUM LIPIDS (ITT–E POOLED ANALYSIS)1

Adapted from Cahn et al, 2018.1

The clinical significance of these values may vary in individual patients.

BONE

  • Statistically significant smaller change in bone turnover markers in the DTG + 3TC arm1

 

STATISTICALLY SIGNIFICANT SMALLER CHANGE IN BONE BIOMARKERS1

BONE TURNOVER MARKERS (ITT–E POOLED ANALYSIS)1

Adapted from Cahn et al, 2018.1

The clinical significance of these values may vary in individual patients.

Interactive Man

Experts Discuss the GEMINI-1 and GEMINI-2 Data

Is it time to rethink the way we treat HIV?

No One Should Take More Medicines Than They Need

All medicines have side effects and the potential to cause harm

A 20-year-old starting a 3-drug regimen may be on therapy for nearly 6 decades, which translates to more than 60,000 doses of individual medications2

Why 2-Drug Regimens?

Is It Time to Rethink the Way We Treat HIV?

Why pair TIVICAY and lamivudine?

The Next Step in the 2-Drug Regimen Era

A complete regimen of just 2 pills powered by dolutegravir at the core

This regimen is only suitable for the treatment of HIV-1 infection where there is no known or suspected resistance to the integrase inhibitor class, or to lamivudine.

Shown superior efficacy vs 5 different ART comparators in 3-drug regimens3-7

Proven effective in a 2-drug regimen with lamivudine in treatement-naive patients at 48 weeks and rilpivirine in virologically suppressed patients at 100 weeks1,8

High barrier to resistance proven in clinical trials up to 144 weeks and real-world settings1,3-9

Favourable Drug-Drug Interaction Profile10

Generally Well Tolerated3-5

Rapid and Sustained Virological Response in Treatment-Naïve Patients10,11

Over 20 years of experience12

Established efficacy and generally well tolerated13-16

Few clinically significant drug-drug interactions13,17

Guidelines recommended since 199818-23

Eliminated at a similar rate to DTG17,24

Would you be confident prescribing TIVICAY + lamivudine to your appropriate treatment-naïve adult patients with HIV?

YES

Thank you for your response.

 

Do you have a colleague who might be interested in learning about DTG + 3TC?

Consider sharing the GEMINI Slide Deck.

NO

Thank you for your response.

Please consider reviewing the GEMINI Slide Deck for a more comprehensive look at the clinical evidence supporting the use of DTG + 3TC in treatment-naïve patients.

UNDECIDED

Thank you for your response.

 

Please consider watching the following video in which Professor Chloe Orkin discuss the clinical relevance of the GEMINI data.

How to Prescribe

 

 

A Convenient Regimen17,24

A Regimen With Few Drug-Drug Interactions17,24

  • Minimal effect on metabolism via the CYP3A4 pathway
  • No known interactions with contraceptives, antihypertensives, proton pump inhibitors, statins, PDE-5 inhibitors or most common recreational drugs*
  • DTG is contraindicated with dofetilide**
  • Avoid chronic co-administration of sorbitol and similar solutions with 3TC
  • Dose separation for antacids and supplements
  • Dose adjustment of DTG required for rifampicin, carbamazepine, oxcarbazepine, phenobarbital, phenytoin and St John's wort
  • Dose adjustment of metformin may be required

 

*This regimen is only suitable for the treatment of HIV-1 infection where there is no known or suspected resistance to the integrase inhibitor class, or to lamivudine.

**dofetilde is an antiarrythmic agent that is not licensed for use in the UK

 

 

 

MAKE TIVICAY + LAMIVUDINE
THEIR FIRST HIV REGIMEN

 

 

POWERFUL
EFFICACY

non-inferior to 
3-drug regimen1

 

 

0 RESISTANCE

up to 48 weeks1

 

 

REDUCED
ARV EXPOSURE

and potential for associated
toxicities1

 

 

BECAUSE NO ONE SHOULD TAKE MORE MEDICINES THAN THEY NEED

 

 

 

 

Studied in HBV-negative patients with viral loads up to 500,000 copies/mL

This regimen is only suitable for the treatment of HIV-1 infection where there is no known or suspected resistance to the integrase inhibitor class, or to lamivudine.

References:

  1. Cahn P, Sierra Madero J, Arribas J, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials., The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.
  2. The Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017;4:e349-e356.
  3. Walmsley S, Baumgarten A, Berenguer J, et al. Dolutegravir plus abacavir/lamivudine for the treatment of HIV-1 infection in antiretroviral therapy-naive patients: week 96 and week 144 results from the SINGLE randomized clinical trial. J Acquir Immune Defic Syndr. 2015;70(5):515-519.
  4. Molina J-M, Clotet B, van Lunzen J, et al; on behalf of the FLAMINGO study team. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. 2015;2(4):e127-e136.
  5. Orrell C, Hagins DP, Belonosova E, et al; on behalf of the ARIA study team. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study. Lancet HIV. 2017;4:e536-e546.
  6. 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.
  7. Aboud M, Kaplan R, Lombaard J, et al. Superior efficacy of dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) compared with lopinavir/ritonavir (LPV/r) plus 2 NRTIs in second-line treatment—48-week data from the DAWNING study. Presented at: International AIDS Conference; July 23-27, 2018; Amsterdam, Netherlands. Poster THPEB040.
  8. Aboud M, Orkin C, Podzamczer D, et al. Durable suppression 2 years after switch to DTG + RPV 2-drug regimen: SWORD-1 and SWORD-2 studies. Presented at: International AIDS Conference; July 23-27, 2018; Amsterdam, Netherlands. Poster THPEB047.
  9. Trottier B, Lake JE, Logue K, et al. Dolutegravir/abacavir/lamivudine versus current ART in virally suppressed patients (STRIIVING): a 48-week, randomized, non-inferiority, open-label, Phase IIIb study. Antivir Ther. 2017;22:295-305.
  10. Min S, Sloan L, DeJesus E, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS. 2011;25:1737-1745.
  11. van Lunzen J, Maggiolo F, Arribas, et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis. 2012;12(2):111-118.
  12. Antiretroviral drugs used in the treatment of HIV infection. http://www.fda.gov/ForPatients/Illness/HIVAIDS/Treatment/ucm118915.htm. Accessed August 9, 2018.
  13. Quercia R, Perno C-F, Koteff J, et al. Twenty-five years of lamivudine: current and future use for the treatment of HIV-1 infection. J Acquir Immune Defic Syndr. 2018;78(2):125-135.
  14. Eron JJ. The treatment of antiretroviral-naive subjects with the 3TC/zidovudine combination: a review of North American (NUCA 3001) and European (NUCB 3001) trials. AIDS. 1996:5;S11-S19.
  15. Bartlett JA, Benoit SL, Johnson VA, et al. Lamivudine plus zidovudine compared with zalcitabine plus zidovudine in patients with HIV infection. Ann Intern Med. 1996:125(3);161-172.
  16. Result summary for NUCB3001. Research Triangle Park, NC. ViiV Healthcare group of companies; September 2, 2005. https://viiv-clinicalstudyregister.com/files2/1561.pdf. Accessed August 9, 2018.
  17. EPIVIR Summary of Product Characteristics. 
  18. US Department of Health and Human Services. Report of the NIH panel to define principles of therapy of HIV infection and guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents; April 24, 1998. https://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL04241998014.pdf. Accessed August 9, 2018.
  19. Carpenter CCJ, Fischl MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society–USA Panel. JAMA. 1998;280(1):78-86.
  20. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. May 30, 2018. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed August 9, 2018.
  21. Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society–USA panel. JAMA. 2018;320(4):379-396.
  22. European AIDS Clinical Society. Guidelines. Version 9.0. October 2017. http://www.eacsociety.org/files/guidelines_9.0-english.pdf. Accessed August 9, 2018.
  23. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Second edition, 2016. Accessed August 9, 2018.
  24. TIVICAY Summary of Product Characteristics.

UK/DTG3TC/0035/18 | November 2018