Does Dovato cause weight gain?

Official answer

by Drugs.com

Yes, Dovato and other integrase inhibitors have been associated with significant weight gain in people living with HIV, although the exact mechanism is not fully understood. Studies have shown that weight gain with dolutegravir can range from 2.4 to 6 kg (5.3 to 13.2 lb), or more, after one year of treatment.

Growing evidence suggests this may result in an increased risk for clinical obesity and metabolic syndrome, including elevated blood sugar, high blood pressure and type 2 diabetes. People living with HIV and taking dolutegravir and lamivudine (the components of Dovato) have reported weight gain. In addition, studies done with the use of Dovato after FDA approval, as well as some other Integrase Strand Transfer inhibitors (INSTIs), have found an association with weight gain. Also, long-term studies of dolutegravir when combined with tenofovir alafenamide have shown significant weight gain.

If you have experienced a rapid or unexpected weight change or have concerns about your weight, contact your doctor for further evaluation. Do not stop your ART treatment unless you have spoken to your healthcare provider due to the risk of building drug resistance, which would make your HIV medicines less effective.

What is Dovato?

In April 2019, Dovato (dolutegravir and lamivudine) was approved as the first complete, two-drug antiretroviral treatment (ART) regimen for untreated HIV in adults OR to replace the current regimen in patients who are:

Dovato contains dolutegravir (Tivicay, DTG), an Integrase Strand Transfer Inhibitor (INSTI) and lamivudine (Epivir, 3TC), nucleoside reverse transcriptase inhibitor (NRTI). Dolutegravir (DTG) is a popular integrase inhibitor because it has a high barrier to resistance, is dosed once daily as an oral tablet and it does not require boosting. Dovato is manufactured by ViiV Healthcare.

Initial FDA approval was based on two clinical trials of more than 1,400 HIV-infected adults with no prior ART treatment. Dovato (dolutegravir and lamivudine) was similarly effective in reducing the amount of HIV in the blood as treatment with dolutegravir (Tivicay) plus emtricitabine and tenofovir disoproxil fumarate (Truvada).

Common side effects with INSTIs such as Dovato include:

ART medicines that contain dolutegravir include:

How much weight gain occurs with Dovato?

Clinical research studies show that weight gain with dolutegravir can range from 2.4 to 6 kg (5.3 to 13.2 lb) after one year of treatment.

Study 1

In a 2019 study of randomized trials published in Clinical Infectious Diseases, researchers looked at weight gain with integrase inhibitors like dolutegravir (found in Dovato) or bictegravir (found in Biktarvy).

Study 2

In a study done in the U.S. from 2007 to 2016 and published in Clinical Infectious Diseases, researchers investigated if weight gain differed among 1,152 people living with HIV who had not received prior treatments (called “treatment-naive”). INSTI-based regimens were compared to other ART regimens.

Study 3

In the NAMSAL study (NCT02777229) researchers conducted a Phase 3 study in treatment-naive adults in Africa with an HIV RNA viral load of greater than 1000 copies per mL. They compared dolutegravir 50 mg with efavirenz 400 mg , both combined with lamivudine and tenofovir disoproxil fumarate (TDF). Results were published in Lancet HIV in Oct. 2020.

Study 4

Studies have found that weight gain can also occur when patients are switched from other ART therapies to one containing dolutegravir. In a study done in four African countries from 2013 to 2020 and published in the Journal of the International AIDS Society, investigators found an association between dolutegravir and weight gain.

Study 5

Significant weight gain has also been reported when dolutegravir is combined with tenofovir alafenamide (TAF), the newer formulation of tenofovir. In the 192-week ADVANCE study (NCT03122262), researchers compared the following treatments in randomized groups of South African patients:

Overall, the treatments were found to be non-inferior (similarly effective) with no differences on kidney or bone parameters. However, significant weight gain was reported in some groups. There was a high risk for metabolic syndrome, associated with increased risk of diabetes, stroke and heart disease, found in 15% of patients taking the DTG / TAF / FTC regimen.

By 192 weeks after randomization, people taking the DTG / TAF / FTC regimen gained roughly 8.9 kg, compared to 5.8 kg for those in the DTG / TDF / FTC group and 3.3 kg in the EFV / TDF / FTC group.

Those taking the TAF regimen with dolutegravir were three times more likely to develop obesity compared to the efavirenz group (a 3.28 hazard ratio), a statistically significant effect. Clinical obesity (BMI ≥ 30) occurred in:

Researchers found that 43% of women developed clinical obesity (compared to 27% of women taking DTG / TDF / FTC and 20% taking EFV / TDF / FTC) by week 192. In addition, 20% of women developed metabolic syndrome, compared to 7% of men.

Significantly more people were likely to develop clinical obesity (BMI ≥ 30) if they were on a regimen containing dolutegravir and tenofovir alafenamide. Overall, by week 192, clinical obesity occurred in:

Why does Dovato cause weight gain?

The mechanism of weight gain with dolutegravir and other Integrase strand transfer inhibitors (INSTIs), such as bictegravir, is not well-defined. Additional clinical studies are needed to determine the exact causes.

Several theories have been suggested as possible mechanisms or risk factors for weight gain with Dovarto or other INSTIs. More than one mechanism may be responsible, and other biological or pharmacological effects not yet identified may come into play.

What are Integrase Strand Transfer Inhibitors (INSTIs)?

Integrase Strand Transfer Inhibitors (INSTIs) include antiretroviral therapies (ARTs) such as dolutegravir and bictegravir. Dovato contains two ART medicines: the Integrase Strand Transfer Inhibitor (INSTI) dolutegravir and the Nucleoside Analogue Reverse Transcriptase Inhibitor (NRTI) emtricitabine.

Integrase Strand Transfer Inhibitors may also be referred to as Integrase Inhibitors.

The Integrase Strand Transfer Inhibitors (INSTIs) drug class includes the following prescription medications:

How does Dovato work?

Integrase strand transfer inhibitors (INSTIs) like Dovato block the action of integrase, an enzyme used by HIV to make copies of itself. Integrase strand transfer inhibitors prevent HIV from multiplying in the host.

This is not all the information you need to know about Dovato (dolutegravir and lamivudine) for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.