#1 Clinical Trials Search in Europe

Dolutegravir

This article examines the use of dolutegravir, an integrase inhibitor drug, in clinical trials for the treatment of HIV infection. Dolutegravir has shown promise in suppressing HIV replication and maintaining viral suppression in both treatment-naive and treatment-experienced patients. The trials discussed here evaluate dolutegravir’s efficacy, safety, pharmacokinetics, and potential side effects when used alone or in combination with other antiretroviral medications.

Table of Contents

What is Dolutegravir?

Dolutegravir (DTG) is a medication used to treat Human Immunodeficiency Virus (HIV) infection. It’s also known by its brand names Tivicay[1] and S/GSK1349572[5]. Dolutegravir belongs to a class of drugs called integrase strand transfer inhibitors (INSTIs), which are important in fighting HIV[3].

How Dolutegravir Works

Dolutegravir works by blocking an enzyme called integrase, which HIV needs to multiply in your body. By stopping this enzyme, dolutegravir helps prevent HIV from making copies of itself and infecting more cells in your body[3]. This action helps to reduce the amount of HIV in your blood (known as viral load) and increase your CD4 cell count. CD4 cells are a type of white blood cell that helps your immune system fight infections[5].

Uses of Dolutegravir

Dolutegravir is primarily used to treat HIV-1 infection in adults and children. It can be used in different scenarios:

  • As part of initial treatment for people newly diagnosed with HIV[5]
  • As a replacement for other HIV medications in people who have achieved viral suppression (very low levels of HIV in the blood) on their current treatment[2]
  • In combination with other antiretroviral drugs to create powerful HIV treatment regimens[1]

Dosage and Administration

Dolutegravir is typically taken as a tablet once or twice daily, depending on your specific situation and treatment plan. The standard dose is usually 50 mg[5]. However, the exact dosage may vary based on factors such as:

  • Whether you’ve taken HIV medications before
  • If you have certain types of HIV that are resistant to other medications
  • If you’re taking other medications that might interact with dolutegravir

It’s crucial to take dolutegravir exactly as prescribed by your healthcare provider[6].

Efficacy and Safety

Clinical trials have shown that dolutegravir is highly effective in treating HIV. It has demonstrated the ability to:

  • Suppress viral replication (stop HIV from making copies of itself)[3]
  • Increase CD4 cell counts, which helps improve the immune system[5]
  • Maintain virological suppression (keep HIV levels very low) in people who switch from other HIV medications[2]

Dolutegravir has shown a high genetic barrier to resistance, meaning it’s less likely that HIV will become resistant to this medication compared to some other HIV drugs[3].

Side Effects and Considerations

Like all medications, dolutegravir can cause side effects. Common side effects may include:

  • Headache
  • Nausea
  • Diarrhea
  • Sleep problems (insomnia)
  • Fatigue

Some studies have reported neuropsychiatric side effects such as anxiety or depression, and there have been concerns about potential weight gain in some patients[3][9]. It’s important to discuss any side effects you experience with your healthcare provider.

There are also some important considerations when taking dolutegravir:

  • It may interact with certain other medications, so always inform your doctor about all drugs you’re taking[4].
  • If you’re pregnant or planning to become pregnant, discuss the risks and benefits of dolutegravir with your healthcare provider[8].
  • Regular monitoring of your viral load and CD4 count is important to ensure the medication is working effectively[9].

Dolutegravir in Combination Therapies

Dolutegravir is often used as part of combination antiretroviral therapy (cART). It can be combined with other HIV medications to create powerful treatment regimens. Some examples include:

  • Dolutegravir + Darunavir/Cobicistat: This combination has been studied as a potential simplified treatment option for people with HIV who have limited treatment options due to drug resistance[1][4].
  • Dolutegravir + Abacavir/Lamivudine: This combination is available as a single tablet called Triumeq[8].
  • Dolutegravir + Tenofovir/Emtricitabine: Another common combination used in HIV treatment[9].

Ongoing Research

Researchers continue to study dolutegravir to better understand its long-term effects, optimal use, and potential in various treatment strategies. Some areas of ongoing research include:

  • Use of dolutegravir as monotherapy (single drug treatment) in certain situations[5].
  • Effects of dolutegravir on bone mineral density[3].
  • How dolutegravir concentrations in different parts of the body (like blood, semen, and rectal tissue) might affect its ability to prevent HIV transmission[6].
  • The relationship between genetic factors, gut microbiota, and response to dolutegravir treatment[9].

These ongoing studies aim to optimize the use of dolutegravir and improve outcomes for people living with HIV.

Aspect Details
Drug Name Dolutegravir (DTG)
Drug Class Integrase strand transfer inhibitor (INSTI)
Common Dosing 50 mg once daily or twice daily
Key Efficacy Findings – Effective viral suppression in treatment-naive and experienced patients – Non-inferior or superior to some other antiretroviral regimens – Effective against some drug-resistant HIV strains
Safety Profile – Generally well-tolerated – Common side effects: headache, nausea, diarrhea, sleep disturbances – Ongoing evaluation of metabolic effects
Special Populations Studied – Treatment-experienced patients with resistance to other drugs – Patients switching from other regimens – Healthy volunteers (for pharmacokinetic studies)
Areas of Ongoing Research – Use as monotherapy – Effects on insulin sensitivity and metabolism – Long-term safety and efficacy

FAQ

  • What is dolutegravir and how does it work? Dolutegravir is an integrase inhibitor drug used to treat HIV infection. It works by preventing the HIV integrase enzyme from inserting viral DNA into human DNA, which stops the virus from multiplying.
  • What are some of the key findings from dolutegravir clinical trials? Clinical trials have shown that dolutegravir is effective at suppressing HIV viral loads, including in patients with resistance to other HIV medications. It has demonstrated non-inferiority or superiority to some other antiretroviral regimens. Some trials are also evaluating its potential as a single-drug regimen.
  • What are the most common side effects of dolutegravir? Common side effects observed in trials include headache, nausea, diarrhea, and sleep disturbances. Some studies are also investigating potential effects on weight gain, insulin sensitivity, and metabolic parameters.
  • How is dolutegravir typically dosed? Dolutegravir is most commonly dosed as a 50 mg tablet taken once daily. Some trials have also evaluated twice daily dosing in certain patient populations.
  • Is dolutegravir effective against drug-resistant HIV? Yes, several trials have shown dolutegravir to be effective in patients with resistance to other antiretroviral drugs, including other integrase inhibitors like raltegravir. Its high genetic barrier to resistance makes it useful for treatment-experienced patients.

Ongoing Clinical Trials on Dolutegravir

  • Study Comparing Doravirine/Lamivudine and Dolutegravir/Lamivudine for HIV Patients with Controlled Viral Load on Three-Drug Regimens

    Recruiting

    3 1 1 1
    Investigated drugs:
    France

  • Study on HIV-1 Patients: Effects of Rilpivirine and Dolutegravir After Stopping Antiretroviral Therapy

    Recruiting

    3 1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy

  • Metformin hydrochloride plus drug combination to reduce pain, inflammation and biological aging in patients with knee osteoarthritis

    Not yet recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    The Netherlands

  • Study on Early Switching to Dolutegravir and Lamivudine for Adults with HIV-1 on Three-Drug Regimen with Virological Suppression

    Not recruiting

    3 1 1 1
    Investigated drugs:
    Italy

  • Study Comparing Weekly Islatravir/Lenacapavir Regimen to Standard Care in HIV Patients with Controlled Viral Load

    Not recruiting

    3 1 1 1
    Investigated drugs:
    Germany The Netherlands Poland Spain

Glossary

  • Integrase inhibitor: A class of antiretroviral drugs that block the action of integrase, an HIV enzyme that inserts the viral genome into the DNA of the host cell.
  • Viral load: The amount of HIV in a blood sample, reported as number of HIV RNA copies per milliliter of blood. It indicates how well treatment is controlling the virus.
  • CD4 count: A measure of the number of CD4 T lymphocytes (white blood cells) per cubic millimeter of blood. It is an indicator of immune system health in HIV patients.
  • Antiretroviral therapy (ART): The use of HIV medicines to treat HIV infection, usually involving a combination of drugs from different classes.
  • Virologic failure: When antiretroviral therapy fails to suppress and sustain a person's viral load to less than 200 copies/mL.
  • Pharmacokinetics: The study of how a drug is absorbed, distributed, metabolized, and eliminated by the body.
  • Genotypic resistance: The presence of specific genetic mutations in HIV that are known to reduce susceptibility to certain antiretroviral drugs.
  • Phenotypic resistance: A laboratory test that measures the ability of HIV to grow in different concentrations of antiretroviral drugs.
  • Monotherapy: Treatment with a single drug, as opposed to combination therapy.
  • Non-inferiority: A type of clinical trial designed to show that a new treatment is not worse than an existing treatment by more than a specified margin.

References

  1. https://clinicaltrials.gov/study/NCT02499978
  2. https://clinicaltrials.gov/study/NCT02219217
  3. https://clinicaltrials.gov/study/NCT01966822
  4. https://clinicaltrials.gov/study/NCT03683524
  5. https://clinicaltrials.gov/study/NCT02401828
  6. https://clinicaltrials.gov/study/NCT01459315
  7. https://clinicaltrials.gov/study/NCT04805944
  8. https://clinicaltrials.gov/study/NCT04229290
  9. https://clinicaltrials.gov/study/NCT03094507
  10. https://clinicaltrials.gov/study/NCT02028819