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

People living with HIV and taking dolutegravir and lamivudine (the components of Dovato) have also reported weight gain. In addition, studies done with the use of Dovato after FDA approval, as well as some other integrase inhibitors, have found an association with weight gain.

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.

Long-term studies of dolutegravir when combined with tenofovir alafenamide have shown weight gain. In the TANGO trial, weight gain was seen in up to 3% of 740 virologically suppressed adults participants after 200 weeks of follow-up (compared to 2% in a tenofovir alafenamide–based (TAF) drug regimen group).

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?

Dovato (dolutegravir and lamivudine) is a complete, two-drug antiretroviral treatment (ART) regimen for adults and and adolescents 12 years of age and older and weighing at least 25 kg who are untreated OR to replace the current regimen in those who are:

• virologically suppressed (HIV-1 RNA less than 50 copies per mL), and
• on a stable antiretroviral regimen with no history of treatment failure, and
• without known substitutions associated with resistance to the individual components of Dovato.

Dovato contains dolutegravir (Tivicay, DTG), an Integrase Strand Transfer Inhibitor (INSTI) and lamivudine (Epivir, 3TC), a 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 in adults 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 may include:

• Anxiety
• Diarrhea
• Headache
• Fatigue (feeling tired, weak)
• Dizziness
• Insomnia (trouble sleeping)
• Mood changes
• Nausea
• Weight gain

ART medicines that contain dolutegravir include:

• Dovato (dolutegravir and lamivudine)
• Juluca (dolutegravir and rilpivirine)
• Tivicay (dolutegravir)
• Triumeq (abacavir, dolutegravir, and lamivudine)

Learn more: HIV and AIDS Medications and Drug Classes

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. The manufacturer also reports a 3% weight gain in a long-term safety study in 740 virologically suppressed adults.

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).

• Researchers discovered that patients on integrase inhibitors gained significantly more weight (3.24 kg [7.1 lbs]) than people taking either an NNRTI or a protease inhibitor.
• A significant weight gain of more than 10% was seen when compared to the beginning of the study.
• The mean weight gain over a 96 week period for dolutegravir was 4.07 kg (95% CI, 3.5 to 4.6 kg), equal to a mean weight gain of about 9 lbs.

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.

• Of the participants, 351 started treatment with INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, 49% were white. BMI was 25.1 kg/m2 at treatment initiation.
• At all study points, weight gain was highest in the dolutegravir groups and found to be significantly different. At 18 months, the average weight gain in the dolutegravir group was 6 kg (13.2 lb) compared to 2.6 kg (5.7 lb) for NNRTIs and 0.5 kg (1.1 lb) for elvitegravir. Those on dolutegravir also gained more weight at 18 months compared to the INSTI raltegravir (3.4 kg [7.5 lb]) and protease inhibitors (4.1 kg [9 lb]), although these differences were not statistically significant.
• The authors conclude that patients first starting treatment with dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based 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.

• The primary efficacy endpoint was defined as the proportion of participants with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin).
• Out of 613 patients, 310 were in the dolutegravir group and 303 were in the efavirenz 400 mg group. The endpoint of non-inferiority was met, meaning the treatments were similarly effective after 96 weeks. Viral load suppression was reached significantly more rapidly in the dolutegravir group (p<0·001). No acquired resistance mutations to dolutegravir were observed.
• Median weight gain was significantly greater in the group of patients receiving dolutegravir (5 kg [11 lb]) compared to the efavirenz group (3 kg [6.6 lb]).
• The incidence of resulting obesity was also greater in the dolutegravir vs. efavirenz group, respectively (22% vs. 16%, p=0.043).

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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.

• Investigators evaluated changes in weight and body mass index (BMI) after switching 1,474 people living with HIV to single tablet tenofovir (TDF) / lamivudine / dolutegravir (known as TLD). Participants remained on the TLD regimen for an average of one year.
• Researchers found that patients receiving TLD had 1.77 times the risk of developing a high BMI (95% CI: 1.22–2.55) compared to patients on non‐TLD ART.
• In the study, participants on tenofovir / lamivudine / dolutegravir gained an average of 0.68 kg (1.5 lbs) more than other compared regimens when adjusted for confounders such as duration of therapy, sex, viral loads or age.
• In the year after switching to TLD, participants had an average weight gain of 1.1 kg / year (2.4 lb), compared to before the switch.

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:

• dolutegravir/tenofovir disoproxil fumarate/emtricitabine (DTG / TDF / FTC)
• dolutegravir/tenofovir alafenamide/emtricitabine (DTG / TAF / FTC)
• efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV / TDF / FTC)

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:

• 29% of patients taking DTG / TAF / FTC
• 21% of patients taking DTG / TDF / FTC
• 15% of patients EFV / TDF / FTC

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:

• 29% of patients taking DTG / TAF / FTC
• 21% of patients taking DTG / TDF / FTC
• 15% of patients EFV / TDF / FTC

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.

• People living with HIV may gain weight once the HIV virus is suppressed and their condition is under better control. In one study, researchers reported that weight gain can be associated with this “return to health” effect in patients who have lived with active HIV disease for years. This is thought to be due to increased catabolism and decreased HIV-associated inflammation.
• Newer medicines for HIV treatment may be associated with less nausea and appetite loss. In addition, prior regimens may have been associated with weight loss.
• In several studies, people who are female at birth have been shown to gain more weight than males at birth.
• Combing dolutegravir with other ART regimens that may cause weight gain (for example, tenofovir alafenamide, TAF)
• A higher baseline body mass index (BMI) at treatment initiation may lead to a greater risk of obesity with dolutegravir
• Changes in the structure of fat cells that may promote obesity
• INSTIs may inhibit melanocyte-stimulating hormone (MSH), which controls appetite
• Genetic enzymes differences

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:

• bictegravir (part of fixed-dose combination), found in Biktarvy
• cabotegravir, found in Vocabria, Cabenuva, and Apretude
• dolutegravir (Tivicay)
• raltegravir (Isentress, Isentress HD)

Related: Does Biktarvy cause weight gain?

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.

References

• Sax PE, Erlandson KM, Lake JE, et al. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis. 2020 Sep 12;71(6):1379-1389. doi: 10.1093/cid/ciz999
• Wood BR, Huhn GD. Excess Weight Gain With Integrase Inhibitors and Tenofovir Alafenamide: What Is the Mechanism and Does It Matter? Open Forum Infect Dis. 2021 Nov 17;8(12):ofab542. doi: 10.1093/ofid/ofab542
• Esber AL, Chang D, Iroezindu M, et al; AFRICOS Study Group. Weight gain during the dolutegravir transition in the African Cohort Study. J Int AIDS Soc. 2022 Apr;25(4):e25899. doi: 10.1002/jia2.25899
• Bourgi K, Rebeiro PF, Turner M, Castilho JL, Hulgan T, Raffanti SP, Koethe JR, Sterling TR. Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy. Clin Infect Dis. 2020 Mar 17;70(7):1267-1274. doi: 10.1093/cid/ciz407
• Calmy A, Tovar Sanchez T, Kouanfack C, et al; New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-Income Countries (NAMSAL) ANRS 12313 Study Group. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon. Lancet HIV 2020; 7:e677–87
• Dovato (dolutegravir and lamivudine)) prescribing information. 4/2024. ViiV Healthcare. Durham, NC. Accessed April 9, 2024 at https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF#page=1
• Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Common and/or Severe Adverse Effects Associated with Antiretroviral Therapy (Table 20). National Institutes of Health (NIH). Accessed Jan 9, 2023 at https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/adverse-effects-antiretroviral-agents-full
• Venter W, Bosch B, Sohkela S, et al. (abstract). Final Week 192 results from the ADVANCE trial: First-line TAF/FTC+DTG, TDF/FTC+DTG vs TDF/FTC/EFV. Accessed Jan 9, 2023. Presented at AIDS 2022. The 24th International AIDS Conference at https://programme.aids2022.org/PAGMaterial/PPT/3733_4919/IAS_ADVANCE_W192POSTER_2022_AQ13JUL22.pdf
• Alcorn K. Dolutegravir and raltegravir cause changes to fat cells. 10/11/2019. AIDSmap.com. Accessed Jan. 9, 2023 at https://www.aidsmap.com/news/nov-2019/dolutegravir-and-raltegravir-cause-changes-fat-cells

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