ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline plc (“GSK”), with Pfizer Inc. and Shionogi Limited as shareholders, today presented three-year results from the TANGO study at IDWeek 2021, being held virtually 29 September - 3 October. Findings showed that the 2-drug regimen (2DR) Dovato (dolutegravir/lamivudine) continued to demonstrate non-inferior efficacy and a high barrier to resistance compared to continuation of tenofovir alafenamide fumarate (TAF)-based regimens of at least three drugs in virologically suppressed adults living with HIV-1 who had not experienced prior virologic failure. At three years, no participants on dolutegravir/lamivudine (0% [0/369]) met confirmed protocol-defined virologic failure, versus three participants (<1% [3/372]) on the TAF-based regimen. No resistance mutations were reported in either arm.
Olayemi Osiyemi, M.D., Founder, CEO, and President of Triple O Medical Services and Triple O Research Institute P.A., United States, lead author and one of the investigators of the TANGO study, said: “These data provide us with further long-term evidence that switching virologically supressed people living with HIV from TAF-based 3-drug regimens to dolutegravir/lamivudine will not only maintain virologic suppression, but offers a treatment option consisting of fewer medicines. As we now consider HIV a long-term condition requiring life-long medication, these results give physicians the data they need to have more confidence in switching their virologically suppressed patients who are taking three or more medicines. Additionally, these data show no confirmed virologic failures, which is important over a long-term study.”
These findings demonstrated the non-inferiority of dolutegravir/lamivudine compared to continuation of TAF-based regimens in the Intention to Treat-Exposed (ITT-E) population (defined as all participants randomised to the study), based on the proportion of participants with plasma HIV-1 RNA ≥50 copies per millilitre (c/mL) at Week 144 (Snapshot virologic failure: 0.3% [1/369] vs 1.3% [5/372]; adjusted difference: -1.1% [95% CI: -2.4%, 0.2%] for the dolutegravir/lamivudine and TAF-based regimen arms, respectively).
In the ITT-E population, both treatment arms showed a high proportion of participants with plasma HIV-1 RNA <50 c/mL, with dolutegravir/lamivudine demonstrating non-inferior virologic suppression to the TAF-based regimen (85.9% [317/369] vs 81.7% [304/372], respectively; adjusted difference: 4.2% [95% CI: -1.1%, 9.5%]).
Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “The latest results from the TANGO study further reinforce Dovato’s role in the HIV treatment landscape, allowing people living with HIV to maintain virologic suppression over the long-term with fewer medicines.”
Overall adverse event (AE) rates were similar between the study arms, with more drug-related grade 2-5 AEs with dolutegravir/lamivudine versus the TAF-based regimens arm (6% [21/369]) vs 4% [13/371], respectively). Rates of AEs were similar between treatment arms at Weeks 48, 96 and 144. The most common drug-related grade 2-5 AEs in the dolutegravir/lamivudine and TAF-based regimens arms were insomnia (1% [4/369] vs 0% [0/371]), increased weight (<1% [3/369] vs <1% [3/371]), constipation (<1% [2/369] vs <1% [1/371]), depression (<1% [2/369] vs <1% [1/371]), flatulence (<1% [2/369] vs 0% [0/371]) and nausea (0% [0/369] vs <1% [2/371]). As with the findings at Weeks 48 and 96, changes in fasting lipids generally favoured dolutegravir/lamivudine.Decreases in total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides were observed in the dolutegravir/lamivudine arm, compared to increases in the TAF-based regimens arm, while very small changes in TC/HDL ratio were seen across both treatment arms. At Week 144, proximal tubular renal function markers were comparable across the two treatment arms.
TANGO is a phase III, randomised, open-label, active-controlled, multicentre study to assess the antiviral efficacy and safety of switching to a 2-drug regimen (2DR) consisting of dolutegravir/lamivudine in HIV-infected adults who are virologically suppressed and stable on a tenofovir alafenamide fumarate (TAF)-based regimen.
Study participants were HIV-1 infected adults on TAF-based regimens with HIV-1 RNA<50 c/mL for at least six months, without prior virologic failure, no historical nucleoside reverse transcriptase inhibitors (NRTI) or integrase inhibitor (INI) major resistance mutation, and no evidence of hepatitis B infection. Participants were randomised to switch to dolutegravir/lamivudine or continue on the TAF-based regimens through Week 148. The primary endpoint was the proportion of participants with a viral load of >50 c/mL at Week 48 (FDA Snapshot algorithm) for the Intention to Treat-Exposed (ITT-E) population. Secondary endpoints included efficacy at Weeks 96 and 144 in the ITT-E and Per Protocol (PP) populations.
About Dovato (dolutegravir/lamivudine)
Dovato is a once-daily, single-pill, 2-drug regimen (2DR) that combines the integrase strand transfer inhibitor (INSTI) dolutegravir (Tivicay, 50 mg) with the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine (Epivir, 300 mg).
Dovato (dolutegravir 50 mg/lamivudine 300 mg tablets) is authorised in the EU for the treatment of HIV-1 infection in adults and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the INSTI class, or lamivudine. In the US, Dovato is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Dovato.
Dovato uses two medicines, instead of the traditional three, to inhibit the viral life cycle at two different sites. INSTIs, like dolutegravir, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Lamivudine is an NRTI that works by interfering with the conversion of viral ribonucleic acid (RNA) into deoxyribonucleic acid (DNA) which in turn stops the virus from multiplying.
Dovato is approved in the US, Europe, Japan, Australia and other countries worldwide.
Trademarks are owned by or licensed to the ViiV Healthcare group of companies.
Important Safety Information for Dovato (50mg dolutegravir/300mg lamivudine) Tablets
DOVATO is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of DOVATO.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.
Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of DOVATO. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.
Do not use DOVATO in patients with previous hypersensitivity reaction to dolutegravir or lamivudine
Do not use DOVATO in patients receiving dofetilide
Warnings and precautions
Embryo Fetal Toxicity:
Lactic Acidosis and Severe Hepatomegaly with Steatosis:
Fatal cases have been reported with the use of nucleoside analogs, including lamivudine. Discontinue DOVATO if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of DOVATO and other drugs may occur (see Contraindications and Drug interactions).
Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of DOVATO.
The most common adverse reactions (incidence ≥2%, all grades) with DOVATO were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%).
Use in specific populations
Please refer to the full European Summary of Product Characteristics for Dovato for full prescribing information, including contraindications, special warnings and precautions for use. For the US, please refer to the US Prescribing Information, including Boxed Warning.
Date: Sep 29, 2021
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