A new era of HIV
treatment starts today

The first single-pill,
2-drug regimen powered by
dolutegravir at the core

Reduce Your Patients’ ARV Exposure

3

Treatment non-inferior to 3-drug regimens at maintaining virological suppression...1

3DR = 2NRTIs + INI/PI/NNRTI

2

is now available with just
2 well-tolerated agents...2-4

1

all in 1 small pill5

JULUCA is indicated for HIV-1 virologically suppressed adults on a stable regimen for at least 6 months with no history of virological failure and no known or suspected substitutions associated with resistance to any NNRTI or INI.

Explore the clinical data

JULUCA—95% of Patients Maintained Virological Suppression

 

                                                       Snapshot virological outcomes at Week 48 (pooled ITT analysis)1

VX_JULUCA_chart_bar 100% 80% 60% 40% 20% 0 95 % 95 % 1 % <1 % 4 % 5 % JULUCA (n=513) Continued 3-drug regimen (2 NRTIs + INI, PI or NNRTI [n=511]) Virological Success (486/513) (485/513) (3/513) (6/513) (24/513) (20/513) No Virological Data Virological Non-response HIV-1 RNA <50 c/mL, % VX_JULUCA_Mobile_chart_bar_1 100% 80% 60% 40% 20% 0 95 % 95 % 1 % <1 % 4 % 5 % Virological Success (486/513) (485/513) (3/513) (6/513) (24/513) (20/513) No Virological Data Virological Non-response HIV-1 RNA <50 c/mL, % JULUCA (n=513) Continued 3-drug regimen (2 NRTIs + INI, PI or NNRTI (n=511))

JULUCA - Non-inferior to continued 3-drug regimens1

Watch: Why DTG + RPV?

 

 

        • In these studies supporting JULUCA, DTG 50 mg + RPV 25 mg were used. Bioequivalence has been demonstrated1

 

JULUCA – ZERO INTEGRASE INHIBITOR RESISTANCE UP TO 48 WEEKS

 

For patients switched to JULUCA, there was no increased risk of virological failure vs continued 3-drug regimen (0.6% vs 1.2%, respectively)1

 

Treatment difference: - 0.5% (95% CI; -1.4, 0.5%); assessed using a non-inferiority margin of -4%1

 

 

    • One NNRTI mutation was identified (K101K/E) in a subject with documented poor/non-adherence1

In studies supporting JULUCA, DTG 50 mg and rilpivirine 25 mg were used. Bioequivalence has been demonstrated.

One Subject With an Identified NNRTI Mutation After Poor/Non-Adherence Resuppressed on DTG + RPV at Week 45

 

    • 41-year-old female participant randomised to DTG + RPV6
    • Viral load history: pre-treatment >2 million copies/mL; at Atripla initiation 968,000 copies/mL6
    • Documented poor/non-adherence leading up to Week 361

 

Juluca_High_barier_to_Resistance 10,000,0001,000,000100,00010,0001,000100101 Screening Day 1 Week 4 Week 8 Week 12 Week 24 Week 36 Week 36Retest Week 45Withdrawal HIV-1 RNA, c/mL 1,059,771 <50 <50 <50 <50 <50 <50 <50 1,018 Resuppressionon DTG + RPV Identified K101K/E mutation (NNRTI)• Confers 1.2. fold change to RPV• RPV phenotypically sensitive

 

Atripla is owned by or licensed to Bristol-Myers Squibb & Gilead Sciences, LLC.

 

JULUCA — Reduce your patients' ARV exposure & potential associated toxicities

JULUCA— Statistically significant Recovery in Bone Mineral Density (Dexa Sub-Study)7

CHANGE_IN_HIP_BMD_TO_WEEK_48 2.0 1.0 0 JULUCA (n=46) Continued 3-drug regimen (n=35) CHANGE IN HIP BMD TO WEEK 48 7 Week 48 % change in BMD 1.34 0.05 P =0.014 2.0 1.0 Week 48 % change in BMD 1.46 0.15 0 P =0.039 CHANGE IN LUMBAR BMD TO WEEK 48 7 CHANGE_IN_HIP_BMD_TO_WEEK_48_mobile 2.0 1.0 0 JULUCA (n=46) Continued 3-drug regimen (n=35) Week 48 % change in BMD 1.34 0.05 P =0.014 CHANGE IN HIP BMD TO WEEK 48 7 CHANGE_IN_LUMBAR_BMD_TO_WEEK_48_mobile JULUCA (n=46) Continued 3-drug regimen (n=35) CHANGE IN LUMBAR BMD TO WEEK 48 7 2.0 1.0 0 Week 48 % change in BMD 1.46 0.15 P =0.039
 

In studies supporting JULUCA, DTG 50 mg and rilpivirine 25 mg were used. Bioequivalence has been demonstrated.

In a DEXA substudy mean bone mineral density (BMD) increased from Baseline to Week 48 in subjects who switched to dolutegravir plus rilpivirine (1.34% total hip and 1.46% lumbar spine) compared with those who continued on treatment with a TDF-containing antiretroviral regimen (0.05% total hip and 0.15% lumbar spine. Any beneficial effect on fracture rate was not studied.5

 

 

Switching to JULUCA provides a robust option for maintaining virological suppression while preserving bone health.7

 

 

 

Bone Health and HIV

Effect of DTG + RPV on Bone Mineral Density in SWORD Studies

JULUCA — For patients who switched to JULUCA. Lipid values remained stable at 48 weeks1

 

 

chart-maintain-lipid 5 4 3 2 1 0 5 4 3 2 1 0 4.83 4.84 4.77 4.81 1.38 1.41 1.35 1.40 2.81 2.78 2.77 2.82 1.43 1.43 1.43 1.33 3.8 3.7 3.8 3.7 JULUCA (n=513) Baseline Week 48 Baseline Week 48 Continued 3-drug regimen (n=511) Total Cholesterol HDL Cholesterol LDL Cholesterol, Calculated Triglycerides Total Cholesteol: HDL Ratio Mean values, mmol/L TOTAL_Cholesterol_mobile 5 4 3 2 1 0 /> 4.83 4.84 4.77 4.81 Total Cholesteol Mean values, mmol/L HDL_Cholesterol_graph_mobile 5 4 3 2 1 0 1.38 1.41 1.35 1.40 HDL Cholesterol Mean values, mmol/L LDL_Cholesterol_Mobile 5 4 3 2 1 0 2.81 2.78 2.77 2.82 LDL Cholesterol, calculated Mean values, mmol/L Triglycerides_mobile 5 4 3 2 1 0 1.43 1.43 1.43 1.33 Triglycerides Mean values, mmol/L Total_Cholesterol_HDL_Ratio_Mobile 5 4 3 2 1 0 3.8 3.7 3.8 3.7 Total Cholesterol: HDL ratio Mean values, mmol/L Juluca_Key_for_graphic_bars JULUCA (n=513) Baseline W eek 48 3-drug_key Baseline Week 48 Continued 3-drug regimen (n=511)

 

No change in eGFR in either group as measured by cystatin C8

 

In studies supporting JULUCA, DTG 50 mg and rilpivirine 25 mg were used. Bioequivalence has been demonstrated.

JULUCA: Two well-tolerated agents in one pill

 

    • Patients switched to JULUCA had a median time on ART of 4.25 years1
    • 87% of subjects were new to both DTG and RPV9

 

Adverse events by Week 48 in SWORD-1 and SWORD-2 (pooled)1,6

 

JULUCA
(n=513)
n (%)
Continued 3-drug regimen
(n=511)
n (%)
Any AE*
395 (77) 364 (71)
Drug-related AEs*
Headache
Diarrhoea
97 (19)
11 (2)
8 (2)
9 (2)
0
1 (<1)
AEs leading to withdrawal from the study 17 (3) 3 (1)

*Reported by 5% or more of participants in either group.1

 

*In studies supporting JULUCA, DTG 50 mg and rilpivirine 25 mg were used. Bioequivalence has been demonstrated.

How to Prescribe

A complete once-daily regimen in the smallest single pill, taken with a meal


JULUCA is for patients who:

  • Are 18 years or over
  • Are virologically suppressed on ARVs for
    at least 6 months
  • Have no history of virological failure
  • Have no known or suspected resistance
    to any INI or NNRTI
     

JULUCA is indicated for HIV-1 virologically suppressed adults on a stable regimen for at least 6 months with no history of virological failure and no known or suspected resistance to any NNRTI or INI.

 

Drug-Drug Interactions5

 

  • No known interactions with contraceptives, statins, PDE-5 inhibitors
  • Contraindicated:
    • Proton pump inhibitors
    • Dofetilide
    • Rifampicin, rifapentine
    • Carbamazepine, oxcarbazepine, phenobarbital, phenytoin
    • Systemic dexamethasone
    • St John's wort
  • H2-antagonists: JULUCA should not be co-administered at the same time. Recommended to be administered 12 hours before or 4 hours after JULUCA. Only H2-receptor antagonists that can be dosed once daily should be used
  • Fe/Ca/Mg/multivitamins: Should be taken with JULUCA, with a meal. If this is not possible then recommended to be 6 hours before or 4 hours after
  • Antacids: JULUCA should not be co-administered at the same time. Recommended to take 6 hours before or 4 hours after
  • Metformin: Dose adjustment of metformin should be considered with co-administration of JULUCA

 

Why DTG + RPV?

Dolutegravir and Rilpivirine: An Innovative Pairing

Like 3-drug regimens, dolutegravir + rilpivirine inhibits the viral life cycle at 2 different target sites2,3

 

DTG + RPV is a robust treatment regimen

 

 

See why the pairing of DTG + RPV is an effective choice for a 2DR

Welcome to the 2-Drug Regimen Era

An Evolution in the Treatment of HIV

With treatment, people living with HIV are now expected to have a near normal life expectancy

Based on results from the Antiretroviral Therapy Cohort Collaboration, a 20-year-old starting HIV therapy during 2008 to 2010 can expect to see their 78th birthday.18

The majority of time on therapy is spent maintaining virological suppression18 

72% of patients still worry about the long-term effects of ARVs on their bodies (800/1,111)19

 

 

Switching patients therapy to 2 drug regimen following suppression can reduce ARV exposure and potential associated toxicities

 

Guidelines & Resources

DTG + RPV now recommended by DHHS and EACS in treatment guidelines

DHHS Guidelines, October 201720

DTG + RPV receives AI recommendation* for switching suppressed patients.
DTG plus RPV can be a reasonable option when the use of NRTIs is not desirable and when resistance to either DTG or RPV is not expected.20

*Strong recommendation based on 1 or more randomised trials with clinical outcomes and/or validated laboratory endpoints.

EACS Guidelines, October 201721

DTG + RPV included as a switch strategy for virologically suppressed patients.

References:

  1. Llibre JM, Hung C-C, Brinson C, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018. 391: 839–49 .
  2. TIVICAY (dolutegravir) Summary of Product Characteristics. March 2018.
  3. Edurant (rilpivirine) Summary of Product Characteristics. August 2017.
  4. TRIUMEQ Summary of Product Characteristics. March 2018.
  5. JULUCA Summary of Product Characteristics. May 2018.
  6. Llibre JM, Hung C-C, Brinson C, et al. SWORD 1 & 2: Switch to DTG + RPV maintains virologic suppression through 48 weeks, a Phase III study. Presented at: Conference on Retroviruses and Opportunistic Infections; February 13-16, 2017; Seattle, WA.
  7. McComsey GA, Lupo S, Parks D, et al. Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health. AIDS. 2018;32:477-485.
  8. Orkin C, Llibre JM, Kahl L, et al. Renal, inflammatory and bone biomarkers following switch to the DTG + RPV 2-drug regimen: the SWORD-1 and SWORD-2 studies. Presented at: 16th European AIDS Conference; October 25-27, 2017; Milan, Italy. Poster BPD2/10.
  9. Oglesby A, Punekar Y, Angelis K, et al. Patient reported outcomes after switching to a 2 drug regimen of dolutegravir + rilpivirine: results from the SWORD-1 and SWORD-2 studies. Presented at: 16th European AIDS Conference; October 25-27, 2017; Milan, Italy. Poster BPD1/2.
  10. 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.
  11. 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.
  12. Orrell C, Hagins DP, Belonosova E, et al. 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. Published online July 17, 2017. Lancet HIV. doi:10.1016/S2352-3018(17)30095-4.
  13. 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/RTV) plus 2 NRTIs in second-line treatment—interim data from the DAWNING Study. Presented at: Annual International AIDS Conference; July 23-26, 2017; Paris, France. Abstract TUAB0105LB.
  14. 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.
  15. Raffi F, Jaeger H, Quiros-Roldan E, et al; on behalf of the extended SPRING-2 Study Group. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013;13(11):927-935.
  16. Pozniak AL, Morales-Ramirez J, Katabira E, et al; TMC 278-C 204 Study Group. Efficacy and safety of TMC 278 in antiretroviral-naïve HIV-1 patients: week 96 results of a phase IIb randomized trial. AIDS. 2010; 24:55-65.
  17. Mills AM, Antinori A, Clotet B, et al; on behalf of the ECHO and THRIVE study groups. Neurological and psychiatric tolerability of rilpivirine (TMC278) vs. efavirenz in treatment-naïve, HIV-1–infected patients at 48 weeks. HIV Med. 2013;14:391-400.
  18. 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;1-9 (published online May 10). http://dx.doi.org/10.1016/S2352-3018(17)30066-8. Accessed 18 July 2017.
  19. Young B, Spire B, Garcia D, et al. Patient experience and views on antiretroviral treatment—findings from the Positive Perspectives study. Presented at: IDWeek 2017; October 4-8, 2017; San Diego, CA. Poster 1393.
  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. October 17, 2017. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed February 12, 2018.
  21. European AIDS Clinical Society. Guidelines. Version 9.0. October 2017. http://www.eacsociety.org/files/guidelines_9.0-english.pdf. Accessed February 12, 2018.

UK/DTGRPV/0034/18(2) | September 2018