Antiretroviral Therapy for Early HIV/AIDS

(DGVTAF Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must be taking: Antiretrovirals

Must not be taking: Immunomodulatory drugs, Investigational drugs

Disqualifiers: Severe kidney disease, Severe hepatic impairment, 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: 6 months

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to identify and provide immediate antiretroviral therapy to a cohort of HIV-infected individuals with very early HIV infection (estimated date of infection within the last 90 days). The primary aim of the study is to evaluate whether initiation of dolutegravir plus emtricitabine/tenofovir during acute/early HIV infection leads to protection of CD4+ T cells and other immune cells in the peripheral blood and lymphoid tissue from infection.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as dofetilide, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John's wort, metformin, and any immunomodulatory or investigational drugs. If you are on blood thinners, you may need to stop them for 5 days before and after each colorectal biopsy.

Is the antiretroviral therapy including Dolutegravir, Tivicay, Emtricitabine, and Tenofovir safe for humans?

Dolutegravir, Tivicay, Emtricitabine, and Tenofovir have been shown to be safe and well-tolerated in humans, with common side effects including diarrhea, nausea, and vomiting. These treatments have been tested in various clinical trials and are generally considered safe for use in adults with HIV. ^{1 2 3 4 5}

How does the drug Dolutegravir, Emtricitabine/Tenofovir differ from other HIV treatments?

This drug combination is unique because Dolutegravir is a new-generation integrase inhibitor that doesn't require boosting, making it simpler to use, and it has a high barrier to resistance, meaning it remains effective against many resistant strains of HIV. ^{2 5 6 7 8}

What data supports the effectiveness of the drug Dolutegravir, Tivicay, Emtricitabine/Tenofovir for early HIV/AIDS?

Research shows that Dolutegravir, when used with Emtricitabine and Tenofovir, is effective in treating HIV, as it maintains viral suppression and is well tolerated. Studies have demonstrated that these drugs, both individually and in combination, are effective in reducing HIV levels in the body and increasing immune cell counts. ^{2 3 5 7 9}

Who Is on the Research Team?

Sulggi Lee, MD PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with very early HIV infection (within the last 90 days), who haven't started or have just begun antiretroviral therapy. Participants must consent to study procedures, not be trying to conceive, and use double contraception when sexually active.

Inclusion Criteria

All participants must agree not to participate in a conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization)

I can follow the medication schedule and attend all study visits.

I will use two forms of birth control for two weeks after stopping the study drug.

Exclusion Criteria

My kidney function is severely impaired.

Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation

Pregnant or breastfeeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Immediate initiation of Dolutegravir plus Emtricitabine/Tenofovir for acutely infected HIV patients

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dolutegravir
• Emtricitabine/Tenofovir

Trial Overview The trial tests if starting a combination of dolutegravir and emtricitabine/tenofovir right after HIV infection helps protect immune cells. It aims to treat participants at the 'hyperacute' stage of HIV.

How Is the Trial Designed?

Group I: Dolutegravir+Emtricitabine/Tenofovir Experimental Treatment 2 Interventions

Dolutegravir 50 mg PO daily plus Emtricitabine 200 mg/Tenofovir alafenamide 25 mg

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

Approved in European Union as Tivicay for:

• HIV-1 infection

Approved in United States as Tivicay for:

• HIV-1 infection

Approved in Canada as Tivicay for:

• HIV-1 infection

Approved in Japan as Tivicay for:

• HIV-1 infection

Approved in Switzerland as Tivicay for:

• HIV-1 infection

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

ViiV Healthcare

Industry Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

In a phase 2 study involving initial antiretroviral therapy, both bictegravir and dolutegravir combined with emtricitabine and tenofovir alafenamide demonstrated excellent efficacy over 60 weeks.

After switching to a single-tablet regimen of bictegravir, all participants maintained viral suppression for 12 weeks in the open-label phase, indicating the treatment's safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir alafenamide. Sax, PE., DeJesus, E., Crofoot, G., et al.[2019]

Dolutegravir is an effective treatment for HIV-1, showing noninferior efficacy compared to other antiretroviral therapies in both treatment-naïve and experienced patients, based on data from 6 clinical trials.

It demonstrates significant potency in patients with multiple-class antiretroviral resistance, achieving a 63% virologic suppression rate by week 8, indicating its potential as a reliable option even in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dolutegravir: An Integrase Strand Transfer Inhibitor for the Treatment of Human Immunodeficiency Virus 1 in Adults. Mercadel, CJ., Skelley, JW., Kyle, JA., et al.[2023]

In a study of treatment-naïve adults living with HIV, both dolutegravir+lamivudine (DTG+3TC) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) achieved high rates of viral suppression after 48 weeks, with 89% and 82.4% of patients respectively reaching a viral load of less than 50 copies/mL.

While both treatment regimens were well-tolerated and showed similar virological efficacy, BIC/FTC/TAF was associated with greater weight gain, indicating a potential side effect that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of dolutegravir+Lamivudine and bictegravir/emtricitabine/tenofovir alafenamide in antiretroviral therapy-naïve patients infected with HIV: preliminary results from clinical practice. Gan, L., Xie, X., Fu, Y., et al.[2023]

Dolutegravir is a new HIV-1 treatment that can be taken once daily without needing additional boosting, showing high effectiveness in achieving viral suppression in both treatment-naive and treatment-experienced patients.

In clinical trials, dolutegravir demonstrated superior or noninferior efficacy compared to other antiretroviral therapies, with a high barrier to resistance and a favorable safety profile, making it a significant option for HIV-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dolutegravir: a review of its use in the management of HIV-1 infection in adolescents and adults. McCormack, PL.[2022]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Emtricitabine/tenofovir disoproxil fumarate: in combination with a protease inhibitor in HIV-1 infection. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Emtricitabine/tenofovir disoproxil fumarate. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir alafenamide. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate single-tablet regimen: a review of its use in HIV infection. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Dolutegravir: An Integrase Strand Transfer Inhibitor for the Treatment of Human Immunodeficiency Virus 1 in Adults. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Comparison of dolutegravir+Lamivudine and bictegravir/emtricitabine/tenofovir alafenamide in antiretroviral therapy-naïve patients infected with HIV: preliminary results from clinical practice. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Efavirenz/emtricitabine/tenofovir disoproxil fumarate: triple combination tablet. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Dolutegravir: a review of its use in the management of HIV-1 infection in adolescents and adults. [2022]