CATIE News

5 September 2019 

Dovato approved in Canada for HIV treatment

  • A new two-in-one pill combines anti-HIV medications dolutegravir and 3TC
  • This is the first dual therapy approved in Canada for initial treatment of HIV
  • Dovato was found as effective as triple-drug regimens with dolutegravir

In August 2019 Health Canada approved the use and sale of a regimen containing the following two anti-HIV medicines:

  • Dolutegravir (Tivicay, also in Juluca and Triumeq) – 50 mg
  • 3TC (lamivudine) – 300 mg

These two drugs will be sold in a pill under the brand name Dovato. Manufactured by ViiV Healthcare, Dovato is a complete treatment in one pill. It is taken once daily, with or without food, day or night. Dovato should be available for ordering by wholesalers and pharmacies in late September 2019.

About Dovato

The drugs inside Dovato are not new. Dolutegravir has been used in Canada since 2013. It belongs to a class of drugs called integrase inhibitors. Over the past seven years, integrase inhibitors have become the cornerstone of combination therapy for HIV in Canada and other high-income countries. When used as part of HIV treatment, regimens containing an integrase inhibitor usually reduce the amount of HIV in the blood more quickly than other regimens. In general, integrase inhibitors are well tolerated. 

The other medicine that makes up Dovato is the nucleoside analogue 3TC (lamivudine). This drug has been used in HIV treatment regimens since the mid-1990s. It is generally safe and a successful part of many regimens.

What is new about Dovato

For the first time, dolutegravir and 3TC are in one pill and this pill is approved for the initial treatment of HIV infection.

Effectiveness

In clinical trials with HIV-positive people, Dovato has been found to be similarly effective to other regimens that contain the integrase inhibitor dolutegravir over a period of 96 weeks (the length of the studies so far). The drugs inside Dovato work well in various groups of people, including women, those using HIV treatment for the first time and those who are treatment experienced.

Safety

Dovato was generally safe in clinical trials. Side effects that occurred were temporary, usually mild to moderate in intensity and affected 5% or less of participants. They included the following:

  • headache
  • diarrhea
  • nausea
  • difficulty falling asleep or staying asleep
  • feeling sleepy during the daytime
  • lack of energy/feeling tired

Note that the people who are typically enrolled in pivotal clinical trials of new HIV treatments are usually young and relatively healthy adults. However, once a treatment is approved and more widely available, it gets used by clinic populations that are usually not in pivotal clinical trials. These people can be older and may have other health issues (comorbidities)—including cardiovascular disease, liver injury, kidney injury, type 2 diabetes, anxiety, depression and substance dependency—that require medications and, in some cases, close clinical and laboratory monitoring. As a result, their experience of side effects may be different than those reported in pivotal clinical trials.

However, 3TC has been in use for nearly 25 years, dolutegravir for almost seven years, and a pill called Triumeq (containing dolutegravir + 3TC + abacavir) has been used for six years, so the side effects of these drugs are well known.

Use

According to Viiv, doctors should bear the following points in mind prior to or when prescribing Dovato:

  • It is meant for use by “adults and adolescents 12 years of age and older weighing at least 40 kg.”
  • “Dovato is not recommended for patients with any known or suspected viral resistance to dolutegravir or lamivudine.”
  • “Dovato is not recommended for use in patients with creatinine clearance less than 50 mL/min as the dose of lamivudine cannot be adjusted.”
  • “Dovato contains lamivudine and therefore it is recommended to test for hepatitis B virus”

Special populations

Pregnant women

Viiv recommends that Dovato not be used during pregnancy “unless the potential benefits outweigh the potential risks to the fetus.”

Older adults (over the age of 65)

Viiv states that clinical trials with Dovato “did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from adult patients less than 65 years of age.”

Pediatrics (under the age of 12)

Viiv states: “Safety and efficacy of Dovato in pediatric patients less than 12 years of age and weighing less than 40 kg have not been established.”

Access

After Health Canada licenses a treatment, physicians can prescribe it but initially patients must pay for it themselves unless they have a private insurance plan that covers the cost. Usually it takes between three and six months for such coverage to take effect.

If left untreated, HIV infection leads to catastrophic disease that can affect one’s ability to work. HIV treatment is expensive. In Canada, provincial and territorial ministries of health heavily subsidize the cost of anti-HIV medications. Each ministry has a listing for the drugs for which it is prepared to pay. These listings are called formularies.

In the months ahead, Viiv and provincial and territorial ministries of health will be negotiating the price of Dovato. This process might not be completed until sometime in 2020. Check with a pharmacist to find out when Dovato is listed on your region’s formulary.

In Canada, Dovato should be ready for ordering by wholesalers and pharmacies towards the end of September, 2019.

A CATIE Factsheet on Dovato is in development. Some information about clinical trials with Dovato is available below. Additional information about Dovato in clinical trials and issues to consider, including safety to the fetus, will be forthcoming on the CATIE website.

Resources

TreatmentUpdate 229

Agencies issue caution about use of dolutegravir by pregnant HIV-positive women – CATIE News

—Sean R. Hosein

REFERENCES:

  1. Viiv Healthcare. Dovato (dolutegravir and lamivudine tablets). Product Monograph. 22 August 2019.
  2. Glaxo Wellcome Biochem Inc. 3TC. Notice of Compliance. 12 August 1995.
  3. Quercia R, Perno CF, Koteff J, et al. Twenty-five years of lamivudine: Current and future use for the treatment of HIV-1 infection. Journal of Acquired Immune Deficiency Syndromes. 2018 Jun 1;78(2):125-135.
  4. Viiv Healthcare. Tivicay (dolutegravir sodium). Notice of compliance. 31 October 2013.