Biktarvy vs. Symtuza for HIV-Related Weight Gain

Overseen By Smit Rajput, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: East Carolina University

Must be taking: Antiretrovirals

Must not be taking: Insulin, Antidepressants, Antipsychotics, others

Disqualifiers: Morbid obesity, Substance abuse, Pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines why some HIV medications might cause more weight gain than others. Researchers compare two treatments, Biktarvy (a combination of bictegravir, emtricitabine, and tenofovir alafenamide) and Symtuza (a combination of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide), to assess their effects on body weight and body mass index (BMI) over 48 weeks. They also investigate the role of micro-RNAs, tiny molecules in the body that can influence gene activity. Participants with HIV who are new to treatment and have access to a smartphone might be suitable for this study. As a Phase 4 trial, this study involves treatments already approved by the FDA and proven effective, aiming to understand how they benefit more patients.

Do I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot be on medications associated with weight changes or those that interact with Symtuza or Biktarvy.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that are known to interact significantly with Symtuza or Biktarvy, as well as those associated with weight loss or gain, like insulin or antidepressants.

What is the safety track record for these treatments?

Research has shown that both Biktarvy and Symtuza have been studied for their safety in people with HIV. Biktarvy, a combination of bictegravir, emtricitabine, and tenofovir alafenamide, was 92% effective over 12 months for people with HIV. Regarding weight changes, participants taking Biktarvy gained an average of 2 kg over 96 weeks, with about 17.3% experiencing weight gain.

Symtuza, which combines darunavir, cobicistat, emtricitabine, and tenofovir alafenamide, also showed low weight gain in studies. Patients on Symtuza gained an average of 2 kg or less over 96 weeks. In two studies, only one person reported weight gain related to the treatment, with an average increase of about 3.13 pounds over 48 weeks.

Overall, both treatments are generally well-tolerated, with weight gain as a noted side effect. These findings suggest that both Biktarvy and Symtuza are safe for managing HIV, with manageable side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Biktarvy and Symtuza are unique because they are single-tablet regimens designed to simplify HIV treatment, which can help improve adherence and outcomes. Biktarvy combines bictegravir, emtricitabine, and tenofovir alafenamide, offering a potent option with a high barrier to resistance. Symtuza, on the other hand, includes darunavir, cobicistat, emtricitabine, and tenofovir alafenamide, providing a comprehensive approach with the added benefit of a boosted protease inhibitor. Researchers are particularly excited about their potential impact on HIV-related weight gain, offering a more tailored approach to managing side effects compared to traditional multi-pill regimens.

What evidence suggests that this trial's treatments could be effective for HIV-related weight gain?

Research has shown that both Biktarvy and Symtuza, studied in this trial, effectively manage HIV. Participants will receive either Biktarvy or Symtuza. One study found Biktarvy to be 92% effective in people with HIV over a year. However, some studies report an average weight gain of up to 2 kg (about 4.4 pounds) over 96 weeks. Symtuza is also effective, particularly for those new to treatment, and typically causes less weight gain compared to some other HIV medications. Both treatments help control the virus but may affect weight differently. ^{1 2 4 6 7}

Who Is on the Research Team?

Paul Cook, MD

Principal Investigator

East Carolina University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HIV and a viral load of at least 1000 copies/ml who haven't started treatment yet. They need internet access via smartphone and must be willing to consent. Excluded are those on weight-altering drugs, bedbound individuals, prisoners, pregnant women, people with extreme obesity or cachexia, or active substance abusers.

Inclusion Criteria

My HIV viral load is 1000 copies/ml or higher.

Have access to a smartphone with internet access

Willing to provide written informed consent

Exclusion Criteria

Pregnant females

My BMI is either 40 or higher, or 20 or lower.

Unwilling or unable to comply with protocol requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Symtuza or Biktarvy once daily to study the effect on microRNA profiles and weight gain

48 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Biktarvy
• Symtuza

Trial Overview The study compares the effects of two HIV medications—Biktarvy and Symtuza—on microRNAs in the body and their potential link to weight gain over 48 weeks. It also looks at calorie intake's role in medication-related weight changes.

How Is the Trial Designed?

Group I: Symtuza Experimental Treatment 1 Intervention

15 subjects will get Symtuza (single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide) once daily.

Group II: Biktarvy Experimental Treatment 1 Intervention

15 subjects will get Biktarvy (single-tablet regimen of bictegravir/emtricitabine/tenofovir alafenamide) once daily.

Biktarvy is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Biktarvy for:

• HIV-1 infection

Approved in United States as Biktarvy for:

• HIV-1 infection

Approved in Canada as Biktarvy for:

• HIV-1 infection

Approved in Japan as Biktarvy for:

• HIV-1 infection

Approved in Switzerland as Biktarvy for:

• HIV-1 infection

Who Is Running the Clinical Trial?

East Carolina University

Lead Sponsor

Trials

111

Recruited

42,400+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Symtuza® is the first single tablet regimen for HIV-1 treatment that combines two nucleos(t)ide analogues and a boosted protease inhibitor, providing a convenient and effective option for patients.

This combination not only shows efficacy against various HIV strains but also reduces the risk of bone and renal toxicity associated with other treatments, making it a safer choice for a wider range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of Symtuza® (DRV/c/FTC/TAF). Curran, A., Navarro, J.[2021]

Symtuza® (cobicistat-boosted darunavir with emtricitabine and tenofovir alafenamide) is the first single-tablet regimen based on a protease inhibitor, offering a convenient option for lifelong HIV treatment that enhances adherence due to reduced pill burden.

This regimen is effective and has a high genetic barrier to resistance, making it suitable for naive patients, especially those at risk of poor adherence and with low potential for drug-drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symtuza® (DRV/c/FTC/TAF) in the management of treatment-naive HIV-patients. Gómez Ayerbe, C., Santos González, J., Palacios Muñoz, R.[2021]

In a study of 5,536 virologically suppressed people with HIV switching to regimens containing tenofovir alafenamide/emtricitabine (TAF/FTC), 18% experienced excessive weight gain of 5% or more within 28 weeks, and 9% gained 10% or more within 54 weeks.

Despite the observed weight gain, there were no statistically significant differences in the risk of excessive weight gain among the different treatment regimens (darunavir/cobicistat, elvitegravir/cobicistat, dolutegravir, or bictegravir), indicating similar safety profiles regarding weight changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excessive Weight Gain: Current Antiretroviral Agents in Virologically Suppressed People with HIV. Hsu, RK., Brunet, L., Fusco, JS., et al.[2023]

In a study of 160 people living with HIV, those starting treatment with the bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) regimen experienced an average weight gain of 3.8 kg and an increase in BMI after 48 weeks, indicating significant weight changes in treatment-naïve individuals.

Individuals switching to the BIC/FTC/TAF regimen also gained weight, averaging 2.8 kg, highlighting that weight gain is a common concern for both new and switching patients on this antiretroviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight gain and metabolic disturbances in people living with HIV who start antiretroviral therapy with, or switch to, bictegravir/emtricitabine/tenofovir alafenamide after 48 weeks of treatment: A real-world prospective study. Mata Marín, JA., Velasco-Penagos, JC., Mauss, S., et al.[2023]

In a study involving 631 treatment-naive adults with HIV-1, the fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was found to be non-inferior to the combination of dolutegravir, abacavir, and lamivudine at week 96, with 88% of participants achieving undetectable HIV-1 RNA levels.

Bictegravir was associated with fewer adverse events compared to dolutegravir, with only 28% of participants reporting drug-related side effects, and no participants discontinuing treatment due to adverse events, highlighting its safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Wohl, DA., Yazdanpanah, Y., Baumgarten, A., et al.[2022]

Symtuza® is a single-tablet regimen combining darunavir, cobicistat, emtricitabine, and tenofovir alafenamide, offering a potent and safe treatment option for HIV, particularly due to its high genetic barrier to resistance and renal safety profile.

Phase 3 studies have shown that Symtuza® is non-inferior to other treatments in achieving and maintaining virologic suppression, making it a preferred choice for patients with previous treatment failures or those needing rapid initiation of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symtuza® in clinical practice. Luis Casado, J., Fontecha, M., Monsalvo, M., et al.[2021]

In a study of 2250 people living with HIV-1, those starting treatment with bictegravir/FTC/TAF (BIC/FTC/TAF) experienced significantly greater increases in body mass index (BMI) and weight compared to those on darunavir/cobicistat/FTC/TAF (DRV/c/FTC/TAF) over 12 months.

Patients on BIC/FTC/TAF were more likely to gain at least 5% or 10% in weight and BMI, indicating that while both treatments are effective, the choice of regimen may impact weight management and overall health in people living with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body mass index increase and weight gain among people living with HIV-1 initiated on single-tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide in the United States. Emond, B., Rossi, C., Côté-Sergent, A., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40197415/

Long-term metabolic changes with bictegravir/emtricitabine ... No significant difference in weight change from baseline to Week 144 was found between bictegravir and DTG, or between B/F/TAF and a non-TAF-containing regimen.

2. academic.oup.com academic.oup.com/ofid/article/12/Supplement_1/ofae631.756/7987346

P-557. Weight Change After Switching from Bictegravir ... There was a median weight gain of 1.3 kg after 1 year of treatment with BIC/FTC/TAF. By year 2, there was a median weight loss of 0.8kg in the ...

3. askgileadmedical.com askgileadmedical.com/docs/biktarvy/biktarvy-weight-changes

Biktarvy® (BIC/FTC/TAF) Weight Changes At Week 96, the median weight gain was 2 kg (IQR: ‑0.9, 5.9), and, from baseline to Week 96, 17.3% of participants experienced weight increases ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11902965/

Change in weight and BMI associated with switching to ... Increased weight has been observed among treatment-naïve-and-experienced people living with HIV initiating bictegravir (BIC) and dolutegravir ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772707625001201

Real-world effectiveness, safety, and health-related quality ... Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) confirmed a high effectiveness of 92% in persons with HIV after 12 months.

6. aidsrestherapy.biomedcentral.com aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-025-00732-w

Long-term metabolic changes with bictegravir/emtricitabine ... Weight gain following treatment initiation was greatest in the first year of treatment and most pronounced in individuals with more advanced HIV at baseline.

7. symtuzahcp.com symtuzahcp.com/symtuza-real-world-data/

Comparing ARV-Related Weight Gain in a Real-World Study This retrospective, longitudinal study of data from electronic medical records was designed to compare ARV-related weight gain in patients who were prescribed ...