LONDON, September 23, 2015 /PRNewswire/ --
ViiV Healthcare today announced 24-week data from the Phase
IIIb/IV STRIIVING study, an open-label study evaluating the
efficacy, safety and tolerability of switching from an
antiretroviral therapy (ART) to the once-daily, fixed-dose
dolutegravir-based regimen, Triumeq®
(abacavir/dolutegravir/lamivudine) in virologically suppressed
adults with HIV-1 (n=274).[1] The study included
(n= 277) adults who remained on their existing ART to 24
weeks. STRIIVING met its primary endpoint, demonstrating that
viral suppression was non-inferior for patients switching to
abacavir/dolutegravir/lamivudine (HIV RNA <50 copies/mL in
intention to treat efficacy (ITTe, primary endpoint; n=551): 85%
(abacavir/dolutegravir/lamivudine) vs. 88% (existing ART) [adjusted
difference -3.4%; 95% CI: -9.1, 2.3], per protocol (PP; n=435): 93%
vs. 93% [adjusted difference -0.3%; 95% CI: -4.9,
4.4]).[1] No patients had protocol defined
virologic failure (confirmed plasma HIV-1 RNA ≥400 copies/mL) and
therefore no patients were evaluated for treatment-emergent
resistance in either arm (ITTe).[1]
Furthermore, statistically, the treatment satisfaction score
improved significantly more for those patients switching to
once-daily abacavir/dolutegravir/lamivudine from their established
regimen, as assessed by the HIV Treatment Satisfaction
Questionnaire (adjusted difference 2.4, 95% CI: 1.3, 3.5;
p<0.001).[1]
"For clinicians, choosing among antiretroviral therapies now
involves balancing efficacy with factors such as tolerability,
dosing, ability to use with other medications, and resistance
profile. These data support the use of once-daily
abacavir/dolutegravir/lamivudine as a treatment option in the
switch setting for appropriate patients," said John Pottage,
MD, Chief Scientific and Medical Officer, ViiV Healthcare.
The STRIIVING study recruited patients switching from a broad
range of protease inhibitor (PI; n=234), integrase strand transfer
inhibitor (INSTI; n=146) and non-nucleoside reverse transcriptase
inhibitor (NNRTI; n=171)-based regimens, with the aim of reflecting
a common clinical situation.[1]
Patients switching to abacavir/dolutegravir/lamivudine reported
more adverse events (AEs) leading to withdrawal compared with those
who continued on their established regimen (ITTe: 4% vs.
0%).[1] The majority of these AEs were Grade I
& 2.[1] The most common AEs (≥ 5%) reported in
patients switched to the abacavir/dolutegravir/lamivudine arm
included cough (5%), diarrhoea (7%), fatigue (7%), headache (5%),
nausea (10%) and upper respiratory tract infection
(7%).[1] The AE profile observed with
abacavir/dolutegravir/lamivudine in the study is in line with
previous studies with dolutegravir-based
regimens.[2],[3],[4],[5],[6]
STRIIVING study design
STRIIVING is a Phase IIIb/IV randomised, open-label,
multicentre, North American study to evaluate the efficacy, safety
and tolerability of switching from an ART regimen to once-daily,
fixed-dose abacavir/dolutegravir/lamivudine in
virologically-suppressed (HIV-1 RNA <50 copies/mL) adults with
HIV-1. Participants were randomised 1:1 to switch to
abacavir/dolutegravir/lamivudine (n=274) or continue on their
current ART (n=277) for 24 weeks. The total number of patients in
the study was 551.[1]
Important Safety Information (ISI) for
Triumeq® (abacavir, dolutegravir and
lamivudine) tablets
The following ISI is based on the Highlights section of the
Prescribing Information for Triumeq. Please consult the full
Prescribing Information for all the labelled safety information for
Triumeq.
BOXED WARNING: RISK OF HYPERSENSITIVITY REACTIONS, LACTIC
ACIDOSIS AND SEVEREHEPATOMEGALY, AND EXACERBATIONS OF HEPATITIS
B
See full Prescribing Information for complete boxed
warning.
- Serious and sometimes fatal hypersensitivity reactions have
been associated with abacavir-containing products.
- Hypersensitivity to abacavir is a multi-organ clinical
syndrome.
- Patients who carry the HLA-B*5701 allele are at high risk for
experiencing a hypersensitivity reaction to abacavir.
- Discontinue Triumeq as soon as a 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 abacavir, NEVER
restart Triumeq or any other abacavir-containing product.
- Lactic acidosis and severe hepatomegaly with steatosis,
including fatal cases, have been reported with the use of
nucleoside analogues.
- Severe acute exacerbations of hepatitis B have been reported in
patients who are co-infected with Hepatitis B Virus (HBV) and Human
Immunodeficiency Virus (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
- Presence of HLA-B*5701 allele.
- Previous hypersensitivity reaction to abacavir, dolutegravir or
lamivudine.
- Co-administration with dofetilide.
- Moderate or severe hepatic impairment.
WARNINGS AND PRECAUTIONS
Patients with underlying hepatitis B or C may be at increased
risk for worsening or development of transaminase elevations with
use of Triumeq. Appropriate laboratory testing prior to initiating
therapy and monitoring for hepatotoxicity during therapy with
Triumeq is recommended in patients with underlying hepatic disease
such as hepatitis B or C.
- 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. Discontinue Triumeq as medically appropriate and
consider dose reduction or discontinuation of interferon alfa,
ribavirin, or both.
- Immune reconstitution syndrome and redistribution/accumulation
of body fat have been reported in patients treated with combination
antiretroviral therapy.
- Administration of Triumeq is not recommended in patients
receiving other products containing abacavir or lamivudine.
ADVERSE REACTIONS
The most commonly reported (≥2%) adverse reactions of at least
moderate intensity in treatment-naïve adult subjects receiving
Triumeq were insomnia (3%), headache (2%), and fatigue (2%).
DRUG INTERACTIONS
Co-administration of Triumeq with other drugs can alter the
concentration of other drugs and other drugs may alter the
concentrations of Triumeq. The potential drug-drug interactions
must be considered prior to and during therapy.
USE IN SPECIFIC POPULATIONS
- Pregnancy: Triumeq should be used during pregnancy only if
the potential benefit justifies the potential risk.
- Nursing mothers: Breastfeeding is not recommended due to
the potential for HIV transmission.
- Triumeq is not recommended in patients with creatinine
clearance less than 50 mL per min.
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.
About Triumeq®
Triumeq is a once-daily dolutegravir-based regimen, containing
the 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.
Please refer to the full US Prescribing Information for
contraindications, special warnings and precautions for
use. [7]
Triumeq is a registered trademark of the ViiV Healthcare group
of companies.
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 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
References
1. Trottier B, Lake J, Logue K et al. Switching to
Abacavir/Dolutegravir/Lamivudine combination (ABC/DTG/3TC FDC) from
a PI, INI or NNRTI based regimen maintains HIV suppression.
Presented at the Interscience Conference on Antimicrobial
Agents and Chemotherapy (ICAAC), 17-21
September 2015, San Diego,
California
2. 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.
3. Pappa K, Baumgarten A, Felizarta F, et al. Dolutegravir (DTG)
+ abacavir/lamivudine once daily superior to
tenofovir/emtricitabine/efavirenz in treatment naïve HIV subjects:
144-week results from SINGLE (ING114467). Abstract presented at:
54th Interscience Conference on Antimicrobial Agents and
Chemotherapy; September 5-9, 2014;
Washington, DC, USA.
4. 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
5. Vavro C, Huang J, Avatapally C, Min S, Ait-Khaled M. Durable
efficacy and limited integrase resistance in subjects receiving
dolutegravir after failing a prior regimen: week 48 results from
VIKING-3. Rev Antiviral Ther Infect Dis. 2014;2:Abstract
O-10.
6. 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. Published online March 2015
http://dx.doi.org/10.1016/S2352-3018(15)00027-2 (Last Accessed
March 2015)
7. Triumeq US label
Cautionary statement regarding forward-looking
statements: GSK cautions investors that any
forward-looking statements or projections made by GSK, including
those made in this announcement, are subject to risks and
uncertainties that may cause actual results to differ materially
from those projected. Such factors include, but are not limited to,
those described under Item 3.D 'Risk factors' in the company's
Annual Report on Form 20-F for 2014.
SOURCE ViiV Healthcare