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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether starting a specific combination of antiretroviral drugs can protect important immune cells in people recently infected with HIV. The treatment involves taking dolutegravir (Tivicay) with emtricitabine/tenofovir daily. Participants must show evidence of HIV infection within the last 90 days and should not have started, or only recently started, any other antiretroviral therapy. This study suits those newly diagnosed with HIV who can adhere to a daily medication routine. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, offering participants the chance to contribute to understanding its benefits for more patients.

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.

What is the safety track record for Dolutegravir and Emtricitabine/Tenofovir?

Research shows that combining dolutegravir with emtricitabine/tenofovir is generally safe and well-tolerated for people living with HIV. One study found that this combination helped 90.3% of participants maintain very low virus levels in their blood, indicating effective treatment without major issues.

Another study found that switching to this treatment did not worsen existing health problems, allowing many to use this combination without severe side effects.

Dolutegravir and emtricitabine/tenofovir are already used to treat HIV and have been tested extensively. This testing confirms their safety for most people. While mild headaches or stomach issues can occur, these side effects are usually not serious.

Overall, existing research supports the safety of this treatment for people with HIV. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Dolutegravir combined with Emtricitabine/Tenofovir for early HIV/AIDS treatment because it offers a potent, once-daily regimen that simplifies therapy. Unlike some older treatments, Dolutegravir is an integrase inhibitor, which means it targets a different part of the HIV life cycle, potentially leading to fewer side effects and reducing the chance of drug resistance. Additionally, the inclusion of Emtricitabine/Tenofovir as a backbone provides a well-tolerated and effective approach, enhancing the overall efficacy of this combination. This combination stands out for its powerful suppression of the virus and ease of adherence, making it an appealing option for early intervention.

What is the effectiveness track record for Dolutegravir and Emtricitabine/Tenofovir in early HIV infection?

Research has shown that the combination of dolutegravir, emtricitabine, and tenofovir, which participants in this trial will receive, effectively treats HIV. Studies have demonstrated that this combination keeps the virus under control for extended periods. In one study, this treatment proved just as effective as other standard options for managing the virus. Another study found it works well as a first choice for new patients starting treatment. This combination helps protect important immune cells, like CD4+ T cells, which are vital for a healthy immune system. Overall, this treatment is trusted and widely used to manage HIV effectively. ^{1 3 4 6 7}

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

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

Pregnant or breastfeeding women

My kidney function is severely impaired.

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 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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7654764/

Efficacy and safety of dolutegravir plus emtricitabine versus ... The combination of DTG with FTC had a similar efficacy in maintaining viral suppression through 48 weeks of treatment as standard combined antiretroviral ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33010240/

Dolutegravir with emtricitabine and tenofovir alafenamide ... ADVANCE compared the efficacy and safety of two antiretroviral first-line combinations (dolutegravir combined with emtricitabine and either tenofovir ...

3. academic.oup.com academic.oup.com/jac/article/80/1/281/7903192

Efficacy of bictegravir/emtricitabine/tenofovir alafenamide ... In studies of intermittent ARV treatment, B/F/TAF maintained viral suppression in 98% of participants through Week 96 when administered 4 or 5 ...

4. thelancet.com thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30099-0/abstract

Fixed-dose combination bictegravir, emtricitabine, and ... At week 144, bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to both dolutegravir-containing regimens for efficacy. In study 1, 256 (82%) ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02607956

NCT02607956 | Study to Evaluate the Safety and Efficacy ... This primary objective of this study is to evaluate the efficacy of a fixed dose combination (FDC) containing bictegravir/emtricitabine/tenofovir ...

6. academic.oup.com academic.oup.com/ofid/article/11/10/ofae560/7777137

Efficacy, Safety, and Tolerability of Switching From Bictegravir ... The DYAD study demonstrated noninferior efficacy of switching to dolutegravir/lamivudine among adults with virologic suppression and bictegravir/emtricitab.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1902824

Dolutegravir plus Two Different Prodrugs of Tenofovir to ... Treatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen.