LONDON, England and
DURBAN, South Africa, July 18, 2016 /PRNewswire/ --
ViiV Healthcare today presented 48-week data from the phase
IIIb, open-label, international, multi-centre ARIA study which
showed superior efficacy for Triumeq®
(dolutegravir/abacavir/lamivudine) compared with atazanavir boosted
with ritonavir (ATV/r) plus tenofovir disoproxil
fumarate/emtricitabine (TDF/FTC) in 495 treatment-naïve women
living with HIV.[1] Results show statistically superior
viral suppression (HIV-1 RNA <50 c/mL) rates at week 48: 82%
versus 71% (adjusted difference 10.5%, 95% CI: 3.1%-17.8%, p=0.005)
respectively.[1] ARIA was a
non-inferiority study with a pre-specified analysis for
superiority. Both non-inferiority and superiority endpoints
were met, with superiority being driven by lower rates of both
virological failures and discontinuations due to adverse events
(AEs) in the dolutegravir/abacavir/lamivudine
group.[1]
(Logo:
http://photos.prnewswire.com/prnh/20160223/336449LOGO )
"Women account for over half of the almost 35 million adults
living with HIV worldwide, yet unfortunately they are consistently
under-represented in HIV clinical trials," said John C Pottage, Jr,
MD, Chief Scientific and Medical Officer, ViiV Healthcare. "For
this reason, we are committed to ensuring that the specific
treatment needs of women are investigated. This trial not only
provides physicians with important additional information about
Triumeq, it also builds on the strong body of evidence supporting
the efficacy of dolutegravir-based regimens in a broad range of
patient populations."
The safety profile of dolutegravir/abacavir/lamivudine was
favourable compared to ATV/r plus TDF/FTC, with fewer
drug-related AEs reported on the
dolutegravir/abacavir/lamivudine arm (33% vs 49%); there were also
fewer AEs leading to discontinuation compared to those in the ATV/r
plus TDF/FTC arm (4% vs 7%).[1]
Drug-related AEs reported in the
dolutegravir/abacavir/lamivudine arm included, nausea (31
individuals / 13%), diarrhoea (12 / 5%), headache (5 / 2%) and
dyspepsia (4 / 2%).[1] In the
ATV/r plus TDF/FTC group, drug-related AEs included nausea (35 /
14%), diarrhoea (18 / 7%), ocular icterus (18 / 7%), dyspepsia (15
/ 6%), headache (14 / 6%) and jaundice (13 /
5%).[1]
There were fewer subjects meeting virologic non-response
criteria (VL >50c/mL) in the dolutegravir/abacavir/lamivudine
arm (6%) compared to the other group (14%) at week
48.[1] Of the women that met
protocol-defined virologic withdrawal criteria, none on the
dolutegravir/abacavir/lamivudine arm had treatment-emergent
resistance mutations to the components of
dolutegravir/abacavir/lamivudine, compared with one in the
comparator group.[1]
About HIV
HIV stands for the Human Immunodeficiency Virus. Unlike some
other viruses, the human body cannot get rid of HIV, so once
someone has HIV they have it for life. There is no cure for HIV,
but effective treatment can control the virus so that people with
HIV can enjoy healthy and productive lives.[2]
About HIV in women
Globally, HIV/AIDS is the leading cause of death for women of
reproductive age (15-44 years old)[3] and infection
rates in young women (aged 15-24) are twice as high as those seen
in young men.[4] Despite the scale of the challenge,
women are routinely under-represented in HIV clinical
trials.[5] This may be in part due to lack of child-care
services, exclusions from study protocols due to the potential for
pregnancy and lack of support in the
home.[5] As a result there are
gaps in our knowledge about issues regarding antiretroviral
treatments that are particular to
women.[5]
ARIA study design
ARIA is a phase IIIb randomised, open-label, international,
multi-centre study designed to demonstrate the non-inferior
antiviral activity of fixed-dose dolutegravir/abacavir/lamivudine
(Triumeq) compared with atazanavir boosted with ritonavir (ATV/r)
plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in
treatment-naïve adult women over 48 weeks.[6]
While ARIA is a non-inferiority study, there was a pre-specified
analysis for superiority. ARIA also evaluated the safety and
tolerability of dolutegravir/abacavir/lamivudine compared to ATV/r
plus TDF/FTC arm.[6] 495
treatment-naïve adult women were enrolled in the
study.[6]
About Triumeq®
Triumeq is a once-daily dolutegravir-based regimen, containing
the un-boosted integrase strand transfer inhibitor (INSTI)
dolutegravir and the nucleoside reverse transcriptase inhibitors
(NRTIs) abacavir and lamivudine.
Two essential steps in the HIV life cycle are replication - when
the virus turns its RNA copy into DNA - and integration - the
moment when viral DNA becomes part of the host cell's
DNA. These processes require two enzymes called reverse
transcriptase and integrase. NRTIs and INSTIs interfere with the
action of the two enzymes to prevent the virus from replicating.
This decrease in replication will lead to less virus being
available to cause subsequent infection of uninfected cells.
The latest data for Triumeq, including the ARIA data presented
at IAC 2016,[1] build on existing
clinical trial data demonstrating that dolutegravir-based regimens
are efficacious and generally well-tolerated in a broad range of
people living with HIV (PLHIV), including treatment-naïve,
treatment-experienced and those who have developed resistance to
multiple HIV
drugs.[7],[8],[9],[10],[11]
Triumeq is a registered trademark of the ViiV Healthcare group
of companies.
Important Safety Information
(ISI) for Triumeq® (abacavir, dolutegravir, and
lamivudine) tablets[12]
Note: this is taken from the US label and local variations
apply. Please refer to applicable local labelling.
FDA Indications and Usage: Triumeq is indicated for the
treatment of human immunodeficiency virus type 1 (HIV-1)
infection.
Limitations of Use:
Triumeq alone is not recommended in patients with:
- Current or past history of resistance to any components of
Triumeq
- Resistance-associated integrase substitutions or clinically
suspected INSTI resistance because the dose of dolutegravir in
Triumeq is insufficient in these subpopulations. See full
prescribing information for dolutegravir
BOXED WARNING: HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS
AND SEVERE HEPATOMEGALY, and EXACERBATIONS OF HEPATITIS B VIRUS
(HBV):
Hypersensitivity Reactions:
- Serious and sometimes fatal hypersensitivity reactions have
occurred with abacavir-containing products
- Hypersensitivity to abacavir is a multi-organ clinical
syndrome
- Patients who carry the HLA-B*5701 allele are at a higher risk
of experiencing a hypersensitivity reaction to abacavir; although,
hypersensitivity reactions have occurred in patients who do not
carry the HLA-B*5701 allele
- Triumeq is contraindicated in patients with a prior
hypersensitivity reaction to abacavir and in HLA-B*5701-positive
patients. All patients should be screened for the HLA-B*5701 allele
prior to initiating therapy or reinitiation of therapy with
Triumeq, unless patients have a previously documented HLA-B*5701
allele assessment
- Discontinue Triumeq as soon as hypersensitivity reaction is
suspected. Regardless of HLA-B*5701 status, permanently discontinue
Triumeq if hypersensitivity cannot be ruled out, even when other
diagnoses are possible
- Following a hypersensitivity reaction to Triumeq, NEVER restart
Triumeq or any other abacavir-containing product
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 HBV have been reported in
patients who are co-infected with HBV and HIV-1 and have
discontinued lamivudine, a component of Triumeq. Monitor hepatic
function closely in these patients and, if appropriate, initiate
anti-hepatitis B treatment
CONTRAINDICATIONS
Triumeq is contraindicated in patients:
- who have the HLA-B*5701 allele
- with prior hypersensitivity reaction to abacavir, dolutegravir,
or lamivudine
- receiving dofetilide (antiarrhythmic)
- with moderate or severe hepatic impairment
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions to Dolutegravir:
- Hypersensitivity reactions have been reported and were
characterized by rash, constitutional findings, and sometimes organ
dysfunction, including liver injury. The events were reported in
<1% of subjects receiving TIVICAY® in Phase 3
clinical trials
- Clinically, it is not possible to determine whether a
hypersensitivity reaction with Triumeq would be caused by abacavir
or dolutegravir. Discontinue Triumeq and other suspect agents
immediately if signs or symptoms of hypersensitivity reaction
develop
Effects on Serum Liver Biochemistries in Patients with
Hepatitis B or C Co-infection:
- Patients with underlying hepatitis B or C may be at increased
risk for worsening or development of transaminase elevations with
use of Triumeq. 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
- Appropriate laboratory testing prior to initiating therapy and
monitoring for hepatotoxicity during therapy with Triumeq are
recommended in patients with underlying hepatic disease such as
hepatitis B or C
Use With Interferon- and Ribavirin-based Regimens:
Hepatic decompensation, some fatal, has occurred in HIV-1/hepatitis
C virus (HCV) co-infected patients receiving combination
antiretroviral therapy and interferon alfa with or without
ribavirin. Patients receiving interferon alfa with or without
ribavirin and Triumeq should be closely monitored.
Immune Reconstitution Syndrome: including the occurrence
of autoimmune disorders with variable time to onset, has been
reported.
Fat Redistribution or accumulation has been observed in
patients receiving antiretroviral therapy.
Myocardial Infarction (MI):
- An observational study showed an increase in MI with abacavir;
a sponsor-conducted, pooled analysis did not show increased risk.
In totality, the available data are inconclusive
- The underlying risk of coronary heart disease should be
considered when prescribing antiretroviral therapies, including
abacavir, and action taken to minimize all modifiable risk factors
(eg, hypertension, hyperlipidemia, diabetes mellitus, smoking)
Use With Certain Antiretroviral Products: Triumeq should
not be administered concomitantly with other products containing
abacavir or lamivudine.
ADVERSE REACTIONS: The most commonly reported (≥2%)
adverse reactions of at least moderate intensity in treatment-naïve
adults receiving Triumeq were insomnia (3%), headache (2%), and
fatigue (2%).
DRUG INTERACTIONS
- Co-administration of Triumeq with certain inducers of UGT1A
and/or CYP3A may reduce plasma concentrations of dolutegravir.
Consult the full Prescribing Information for Triumeq for more
information
- Administer Triumeq 2 hours before or 6 hours after taking
polyvalent cation-containing antacids or laxatives, sucralfate,
oral supplements containing iron or calcium, or buffered
medications. Alternatively, Triumeq and supplements containing
calcium or iron can be taken with food
USE IN SPECIFIC POPULATIONS
- Pregnancy Category C: Triumeq should be
used during pregnancy only if the potential benefit justifies the
potential risk. An Antiretroviral Pregnancy Registry has been
established
- Nursing Mothers: Breastfeeding is not recommended
due to the potential for HIV transmission and the potential for
adverse reactions in nursing infants
- Patients with Impaired Renal Function: Triumeq is not
recommended in patients with creatinine clearance <50
mL/min
- Patients with Impaired Hepatic Function: If a dose
reduction of abacavir, a component of Triumeq, is required for
patients with mild hepatic impairment, then the individual
components should be used
Full US Prescribing Information for Triumeq is available at:
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 by GlaxoSmithKline
(LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances
in treatment and care for people living with HIV. Shionogi (TYO:
4507) joined in October 2012. The
company's aim is to take a deeper and broader interest in HIV/AIDS
than any company has done before and take a new approach to deliver
effective and new HIV medicines, as well as support communities
affected by HIV. For more information on the company, its
management, portfolio, pipeline, and commitment, please
visit http://www.viivhealthcare.com
1. C. Orell et al. Superior efficacy of
dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) fixed dose
combination (FDC) compared with ritonavir (RTV) boosted atazanavir
(ATV) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in
treatment-naïve women with HIV-1 infection (ARIA Study). Presented
at the International AIDS Conference (IAC), 18-22 July 2016, Durban, South Africa. Abstract
#10215.
2. World Health Organization (WHO). 2016. HIV/AIDS media fact
sheet. Available at:
http://www.who.int/mediacentre/factsheets/fs360/en/ Last
accessed July 2016.
3. UNAIDS, 2016-2021 Strategy On the Fast-Track to end AIDS.
Available at:
http://www.unaids.org/sites/default/files/media_asset/20151027_UNAIDS_PCB37_15_18_EN_rev1.pdf
Last accessed July 2016.
4. UNAIDS Factsheet - Adolescents, young people and HIV.
Available at:
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. Mirjam et al. A Systematic Review of the Inclusion
(or Exclusion) of Women in HIV Research: From Clinical Studies of
Antiretrovirals and Vaccines to Cure Strategies. Journal of
Acquired Immune Deficiency Syndromes (JAIDS). 2016 Feb 1;71(2):181-8.
6. ClinicalTrials.gov (NCT01910402). Available at:
https://clinicaltrials.gov/ct2/show/NCT01910402 Last accessed
June 2016.
7. Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E,
Gatell JM, Baril J-G, Domingo P, Brennan C, Almond S, Min S, for
the 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.
8. Walmsley S, Baumgarten A, Berenguer J, et al. Brief Report:
Dolutegravir plus abacavir/lamivudine for the treatment of HIV-1
infection in Antiretroviral therapy-naïve patients: Week 96 and
Week 144 Results from the SINGLE randomized clinical trial. Journal
of Acquired Immune Deficiency Syndromes (JAIDS).
2015;70(5):515-519.
9. Molina J, et al. 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:e127-136.
10. Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C,
Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal
M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB,
Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S,
for 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.
11. Castagna S, et al. Dolutegravir in
antiretroviral-experienced patients with raltegravir- and/or
elvitegravir-resistant HIV-1: 24-week results of the Phase III
VIKING-3 study. J Infect Dis. 2014;210:354-62.
12. Triumeq® (dolutegravir/abacavir/lamivudine) US prescribing
information. Available at:
https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Triumeq/pdf/TRIUMEQ-PI-MG.PDF
SOURCE ViiV Healthcare