LONDON, England and Durban, South Africa, 18th July 2016 / PRNewswire / - Today ViiV Healthcare presented 48-week data from the Phase I...
LONDON, England and Durban, South Africa, 18th July 2016 / PRNewswire / -
Today ViiV Healthcare presented 48-week data from the Phase IIIb, open multiple ARIA international study, the superior efficacy to Triumeq® demonstrated (Dolutegravir / abacavir / lamivudine) compared to atazanavir with ritonavir increases (ATV / r) and disoproxil / emtricitabine tenofovir (TDF / FTC) in 495 previously untreated women living with HIV [1], the results of a statistically superior viral suppression (HIV-1 - RNA <50 c / ml) rate show week 48 :. 82% compared to 71% (adjusted difference of 10.5%; 95% CI: 3.1% -17.8%, p = 0.005). ARIA respectively [1] was a non - inferiority study of a predetermined analysis for superiority. Non - inferiority and superiority were achieved both ends, with superiority virological failure is driven and are lower due to adverse events (AEs) in the group / Dolutegravir / lamivudine abacavir rate [1].
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"Women make up more than half of the nearly 35 million adults living with HIV in the world, but are still unfortunately under-represented in HIV clinical trials," she said pottage John C Jr MD, scientific and medical director of ViiV Healthcare. "For this reason we are obliged to be examined to ensure that a specific treatment needs of women. This test not only provides physicians with important information about Triumeq, but also on the strong body of evidence based on the efficacy of regimens containing Dolutegravir to assist in a wide range of patient groups. "
The profile for Dolutegravir / abacavir / lamivudine safety was low compared to ATV / r TDF / FTC, with fewer side effects related to the drug in / Dolutegravir arm abacavir / lamivudine (33% vs 49%); There were also fewer side effects to a termination cause compared to those in the / r arm ATV TDF / FTC (4% vs. 7%). [1]
Drug-related adverse events in the Dolutegravir arm / abacavir / lamivudine are nausea (31 persons / 13%), diarrhea (12/5%), headache (02.05%) and dyspepsia (02.04%) reported. [1] in the ATV / r group / FTC, TDF, the EA-drug - related were nausea (35/14%), diarrhea (18/7%), ocular icterus (18/7%), dyspepsia (15/6%), headache ( 14/6%), and jaundice (13/5%). [1]
There was hit less subjects, the criteria for the absence of virologic response (VL> 50 c / ml) in the / Dolutegravir arm abacavir / lamivudine (6%) compared to the other group (14%) at week 48 women. [ 1], met the criteria set out in the protocol for virological retreat showed no on the arm of abacavir Dolutegravir / / lamivudine - resistance -. mutations processing components thresholds Dolutegravir / abacavir / lamivudine, compared to the control group [1]
HIV
HIV is HIV. Unlike other viruses, the human body can not get rid of HIV obtained so that a person HIV for life does have. There is no cure for HIV, but effective treatment of the virus for people with HIV can live control can lead a healthy and productive life. [2]
HIV in women
Globally, HIV / AIDS is the leading cause of death in women of reproductive age (15-44 years) [3] and the infection rates in young women (15-24) are two. Times that observed in young men [4] Despite the scale of the challenge that women are systematically under -. represented in clinical trials of HIV [5] This is may be due in part to lack of care, study protocols without because of the possibility of pregnancy and a lack of support at home. [5] as a result there are gaps in our knowledge of issues related with antiretroviral treatment related specifically to women. [5]
ARIA Design Study
ARIA is a randomized, multicenter IIIb, open-label, international phase of the non-inferiority fixed dose antiviral activity Dolutegravir / abacavir / lamivudine (Triumeq) compared to atazanavir with ritonavir (ATV / r) and tenofovir disoproxil strengthened to demonstrate fumarate / emtricitabine (TDF / FTC) not previously treated women in adults over 48 weeks [6] while ARIA is not. - Inferiority study, there was a predetermined analysis for superiority. ARIA also assessed the safety and tolerability of Dolutegravir / abacavir / lamivudine compared to ATV / r arm TDF / FTC. [6] 495 untreated adult women were enrolled in the study. [6]
About Triumeq ®
Triumeq's regime Dolutegravir once on a daily basis the inhibitor Dolutegravir chain transfer (INSTI) and unpowered integrase inhibitors containing nucleoside reverse transcriptase abacavir and lamivudine (NRTI).
Two essential steps in the HIV life cycle replication - when the virus's RNA rotates in DNA copy - and integration - when the virus DNA part of the DNA of the host cell. These methods require two enzymes known as reverse transcriptase and integrase. INSTIs NRTIs and with the effect of the two enzymes interfere with viral replication to inhibit. This decrease in replication will result in less virus than is available to cause a new infection of uninfected cells.
Triumeq recent data, including data in the IAC ARIA 2016 [1] shows relying on data from clinical trials that existing Dolutegravir - based diets are effective and generally well tolerated in a wide range of people living with HIV (PLHIV), including have developed resistance to multiple drugs for HIV prior antiretroviral therapy, treatment with experience and those. [7], [8], [9], [10] [11]
Triumeq is a registered trademark of the ViiV Healthcare group of companies.
Imp ortant Security Information (ISI) for Triumeq® (abacavir, lamivudine and Dolutegravir) [12]
Note: This is taken from the US label and local variations apply. Please check the applicable local labeling.
FDA indications and usage: Triumeq is for the treatment of human immunodeficiency - virus 1 (HIV-1) infection indicated.
Use Limitations:
It triumeq alone is not recommended in patients:
- current or past history of resistance to any of the ingredients of Triumeq
- Integrase resistance or clinically INSTI resistance substitutions suspected because Dolutegravir dose Triumeq is insufficient in these populations. See full prescribing information for Dolutegravir
Box - Warning: hypersensitivity reactions, lactic acidosis and severe hepatomegaly and exacerbations of hepatitis - B - Virus (HBV)
Hypersensitivity reactions:
- Serious and occasionally fatal hypersensitivity reactions have been encountered with products containing abacavir
- Hypersensitivity to abacavir is a multi-organ clinical syndrome
- Patients HLA-B * 5701 are more likely to experience a hypersensitivity reaction to abacavir; although hypersensitivity reactions have occurred in patients who are not carriers of the HLA-B * 5701
- Triumeq contraindicated before and HLA-B * 5701-positive patients in patients with a hypersensitivity reaction to abacavir. All patients should be on the HLA-B * 5701 before starting or restarting treatment Triumeq treatment unless patients have HLA-B * 5701 previously documented assessment be screened
- Triumeq interrupted as soon as a hypersensitivity reaction is suspected. Regardless of HLA-B * 5701, permanently suspend Triumeq if hypersensitivity can not be ruled out, even when other diagnoses are possible
- Following a hypersensitivity reaction to Triumeq, NEVER restart Triumeq or another product containing abacavir
Lactic acidosis and severe hepatomegaly with steatosis:
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues
Exacerbations of hepatitis B:
- Severe acute exacerbations of hepatitis B have been reported in patients with component coinfection with HBV and HIV-1 and are no longer lamivudine, a Triumeq. to monitor liver function closely in these patients and, if necessary, to initiate the treatment against hepatitis B
CONTRA - AREAS
Triumeq contraindicated in patients with:
- that have the HLA-B * 5701
- Hypersensitivity reaction to abacavir or lamivudine prior Dolutegravir
- receive dofetilide (antiarrhythmic)
- moderate or severe hepatic dysfunction
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions to Dolutegravir:
- Hypersensitivity reactions have been reported and characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver damage. The events have been reported in <1% of patients treated TIVICAY ® in Phase 3 clinical trials reported
- Clinically, it is impossible to determine whether a hypersensitivity reaction with Triumeq of abacavir or Dolutegravir caused. Stop Triumeq and other suspects agents immediately if signs or symptoms of hypersensitivity reactions develop
Serum biochemical effects on the liver in patients with hepatitis B or C co-infection:
- may be patients with hepatitis B or C Underlying with an increased risk of deterioration or transaminase level development with Triumeq. In some cases, elevations of transaminases with immune reconstitution syndrome or reactivation of hepatitis B, especially in the environment in the treatment of hepatitis has been withdrawn
- appropriate laboratory tests before starting treatment and during treatment with Triumeq hepatotoxicity monitoring in patients with liver underlying disease, such as hepatitis B or C recommended
Use with therapies based on interferon with ribavirin and hepatic decompensation, some fatal, in patients / HIV-1 virus hepatitis - C - virus (HCV) coinfection occurred antiretroviral therapy of interferon alpha and with or without ribavirin. Patients should be monitored closely with interferon alfa with or without ribavirin and Triumeq.
Immune reconstitution syndrome: including the development of auto - immune diseases with variable time to onset, has been reported.
Redistribution or accumulation of fat was observed in patients who observed antiretroviral therapy.
Myocardial infarction (MI):
- An observational study showed an increase in MI with abacavir; Sponsor conducted a pooled analysis showed no increased risk. Taken together, the available data are not conclusive
- The underlying risk of coronary heart disease should be considered when antiretroviral therapies prescribe to keep up with abacavir and action all modifiable risk factors as low as possible (eg, hypertension, hyperlipidemia, diabetes, smoking)
The use of certain antiretroviral products: Triumeq should not be administered concurrently with other products that abacavir or lamivudine.
Side effects: not treated The most common side effects of at least moderate intensity in adults previously receiving Triumeq were insomnia (3%), headache (2%) and fatigue (2 (2%)%?).
INTERACTIONS
- The Triumeq concomitant use with certain inducers UGT1A and / or CYP3A may reduce the plasma concentration of Dolutegravir. Full prescribing information for more details Triumeq
- Manage Triumeq. 2 hours before or 6 hours after antacids containing polyvalent cations, or laxatives, sucralfate, oral supplements containing iron or calcium or buffered medications Alternatively Triumeq and dietary supplements can be taken with calcium or iron in the diet,
USE IN certain population
- Pregnancy Category C: Triumeq be used during pregnancy only if the potential benefit justifies the potential risk. A replay of the Antiretroviral Pregnancy was established
- Breastfeeding: Breastfeeding is not because of the potential for HIV - recommended transmission and the risk of side effects in infants
- Patients with renal impairment: Triumeq is contraindicated in patients with creatinine - clearance <50 ml / min
- Hepatic: If a dose reduction of abacavir, a Triumeq component for patients with mild hepatic impairment, the individual components must be used
The full prescribing information available at Triumeq: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Triumeq/pdf/TRIUMEQ-PI-MG.PDF
About ViiV Healthcare
ViiV Healthcare is a global specialist HIV company established in November 2009, specializing GlaxoSmithKline (LSE: GSK) and Pfizer (NYSE: PFE) offer dedicated to advances in treatment and care of people living with HIV. Shionogi (TYO: 4507) has been the goal of the company is established in October 2012. to take a deeper and broader interest in HIV / AIDS than any company has done before, and take effective to provide a new approach and new drugs available HIV and support communities. of HIV. For more information about the company, its management, portfolio, pipeline and commitment, see http://www.viivhealthcare.com
1. Orell C. et al. the superior efficacy of Dolutegravir / abacavir / lamivudine (DTG / ABC / 3TC) fixed-dose combination (FDC) compared to ritonavir (RTV), atazanavir (ATV) and fumarate / emtricitabine tenofovir disoproxil fumarate (TDF / FTC) in women without treatment infected HIV-1 ( study ARIA). Presented at the International AIDS - Conference (IAC) 18-22 July 2016 in Durban, South Africa # 10215 abstract..
2. World Health Organization (WHO). 2016. HIV / AIDS Media Backgrounder. Available in: http://www.who.int/mediacentre/factsheets/fs360/en/ Last Accessed July 2016.
3. UNAIDS Strategy 2016-2021 to end the fast lane AIDS. Available in: http://www.unaids.org/sites/default/files/media_asset/20151027_UNAIDS_PCB37_15_18_EN_rev1.pdf Last Accessed July 2016.
4. UNAIDS Backgrounder - adolescents, youth and HIV. Available in: http://www.unaids.org/sites/default/files/en/media/unaids/contentassets/documents/factsheet/2012/20120417_FS_adolescentsyoungpeoplehiv_en.pdf Last accessed July 2016.
5. Curno, J. et al Mirjam. A systematic review of the inclusion (or exclusion) of women in HIV research: clinical trials of antiretroviral drugs and vaccines to treat strategies. Journal of Acquired Immune Deficiency Syndromes (JAIDS). 1 February 2016. 71 (2):. 181-8.
6. ClinicalTrials.gov (NCT01910402). Available in: https://clinicaltrials.gov/ct2/show/NCT01910402 June 2016 fetched.
7. Raffi F, H Jaeger, Quiros-Roldan E, H Albrecht, Belonosova E, Gatell JM, JG Baril, Domingo P, C Brennan, Mandel S, S min, the SPRING-2 Study Group. Dolutegravir once daily compared to raltegravir twice daily in antiretroviral treatment-naïve adults with HIV-1 (SPRING-2 study) 96 weeks results from a double-blind, randomized, non-inferiority. Lancet Infect Dis. 2013; 13 (11): 927-935.
8. Walmsley S, A Baumgarten, Berenguer J, et al. Brief Report: Dolutegravir and abacavir / lamivudine for the treatment of HIV-1 in patients with previous antiretroviral therapy: 96 weeks Week 144 results single randomized clinical trial. Journal of Acquired Immune Deficiency Syndromes (JAIDS). 2015; 70 (5): 515-519.
9. Molina J, et al. Once a day, compared to Dolutegravir darunavir and ritonavir for adults without prior treatment with HIV-1 (Flamenco) 96 weeks the results of a randomized Phase 3b open. Lancet HIV. 2015; 2: e127-136.
10. P Cahn, Pozniak AL, Mingrone H, Shuldyakov A, C Brites, Andrade Villanueva-JF, G Richmond, BC Buendia, Fourie J, M Ramgopal Hagins D Felizarta F, J Madruga, Reuter T, T Newman, Klein CB , J Lombaard, Grinsztejn B, D Dorey, Under M, S Griffith, min S, the extended study team of navigation. Dolutegravir to raltegravir in adults with antiretroviral drugs, integrase inhibitors for HIV without treatment: 48 weeks of randomized results, double-blind, non-inferiority of sailing. Lancing. 2013; 382 (9893): 700-708.
11. Castagna S, et al. Dolutegravir in pretreated patients without treatment with raltegravir and / or HIV-1 strains resistant to elvitegravir 24 weeks for Phase III-3 VIKING study. J Infect Dis. 2014; 210: 354-62.
12. Triumeq® (Dolutegravir / abacavir / lamivudine) US prescribing information. Available in: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Triumeq/pdf/TRIUMEQ-PI-MG.PDF
