Novel Antiretroviral Therapy for HIV

Recruiting at 61 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must not be taking: Long-acting ARVs

Disqualifiers: AIDS, Active infections, Liver cirrhosis, HCV, HBV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 11 days

49 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing new medicines to stop HIV from multiplying in people living with HIV. The goal is to find effective treatments to manage their infection and improve their health.

Will I have to stop taking my current medications?

The trial protocol requires that any prescription or over-the-counter medications, including herbal products, taken within 28 days before starting the study drug must be reviewed and approved by the sponsor, except for vitamins, acetaminophen, and ibuprofen. This means you might need to stop or adjust some of your current medications.

What data supports the effectiveness of the drug B/F/TAF for treating HIV?

B/F/TAF is a combination drug that is highly effective for treating HIV due to its ability to quickly reduce the virus in the body, its good safety profile, and its minimal interactions with other drugs. It is recommended for rapid initiation of treatment, even in patients with advanced HIV, and has shown effectiveness in maintaining virus control in both adults and children. ^{1 2 3 4 5}

Is the novel antiretroviral therapy B/F/TAF safe for humans?

B/F/TAF is generally well tolerated and has shown improved safety for bones and kidneys compared to older treatments. It has fewer side effects and drug interactions, making it a safer option for long-term use in people with HIV. ^{1 3 6 7 8}

What makes the drug B/F/TAF unique for treating HIV?

B/F/TAF is unique because it combines three drugs into a single, small tablet that is easy to take, has fewer side effects, and interacts less with other medications. It also works well in children and has a high barrier to resistance, meaning the virus is less likely to become resistant to it. ^{1 3 4 6 9}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with HIV-1 who have a certain level of viral load, CD4 cell count above 200 cells/mm^3, and good kidney function. They should be new to the drug class being tested or haven't taken any antiretrovirals in the last 12 weeks. People can't join if they've had AIDS-defining conditions, resistance to major ARV classes, hepatitis B or C infections, significant liver issues, are pregnant/breastfeeding, need prohibited medications or have serious health problems.

Inclusion Criteria

Willing and able to comply with meal requirements on dosing days

Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 5000 copies/mL but ≤ 400,000 copies/mL at screening

Cluster of differentiation 4 (CD4) cell count > 200 cells/mm^3 at screening

Exclusion Criteria

I am not on any medications that the study does not allow.

I have had an AIDS-defining condition.

Hepatic transaminases (aspartate aminotransferase (AST) or alanine aminotransferase (ALT)) > 5 x upper limit of normal (ULN)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of the study drug (bavtavirine, GS-1720, or GS-6212) followed by assessments and initiation of a standard antiretroviral regimen

11 days

Multiple visits for assessments and drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants continue on a standard antiretroviral regimen for additional monitoring

Up to Day 39 for Substudy 01, Day 60 for Substudy 02, and Day 25 for Substudy 03

Treatment Details

Interventions

• B/F/TAF
• GS-1720
• GS-5894
• Standard of Care

Trial Overview The study tests novel antiretrovirals GS-5894 and GS-1720 against standard HIV treatments in two substudies. Participants will start on a standard care regimen after Day 11. The aim is to see how these new drugs affect HIV-1 levels compared to usual treatments.

Participant Groups

Group I: Substudy 03: Cohort 1: GS- 6212 100 mg Experimental Treatment 3 Interventions

Participants receive GS-6212 100 mg tablet twice daily on Days 1 through 10. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 25.

Group II: Substudy 02: Cohort 4: GS-1720 900 mg Experimental Treatment 3 Interventions

Participants receive a single dose of GS-1720 900 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Group III: Substudy 02: Cohort 3: GS-1720 30 mg Experimental Treatment 3 Interventions

Participants receive a single dose of GS-1720 30 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Group IV: Substudy 02: Cohort 2: GS-1720 150 mg Experimental Treatment 3 Interventions

Participants receive a single dose of GS-1720 150 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Group V: Substudy 02: Cohort 1: GS-1720 450 mg Experimental Treatment 3 Interventions

Participants receive a single dose of GS-1720 450 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Group VI: Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal) Experimental Treatment 3 Interventions

Participants receive bavtavirine 900 mg tablet with a high-fat meal on Days 1 and 2. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.

Group VII: Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal) Experimental Treatment 3 Interventions

Participants receive a single dose of bavtavirine 1200 mg tablet with a low-fat meal on Day 1. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.

Group VIII: Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal) Experimental Treatment 3 Interventions

Participants receive a single dose of bavtavirine 675 mg tablet with a high-fat meal on Day 1. After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of B/F/TAF, or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 39.

Who Is Running the Clinical Trial?

Gilead Sciences

Lead 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

Findings from Research

In a study of ART-naive adults, the tenofovir alafenamide (TAF) regimen showed similar viral suppression rates to the tenofovir disoproxil fumarate (TDF) regimen at 24 weeks, but had a slightly lower rate at 48 weeks due to higher discontinuation rates in the TAF group.

TAF demonstrated significantly better renal and bone safety profiles compared to TDF, with less proteinuria and less reduction in bone mineral density, making it a promising option for initial HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study. Mills, A., Crofoot, G., McDonald, C., et al.[2022]

In a Phase 2 study involving 170 antiretroviral naive adults, both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) showed high rates of virologic suppression in HIV-1 patients after 48 weeks, with 88.4% and 87.9% respectively achieving less than 50 copies of HIV RNA per milliliter.

Patients treated with TAF experienced significantly less impact on kidney function and bone mineral density compared to those treated with TDF, indicating a potentially safer profile for TAF in terms of renal and bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. Sax, PE., Zolopa, A., Brar, I., et al.[2022]

References

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

Profile of bictegravir/emtricitabine/tenofovir alafenamide fixed dose combination and its potential in the treatment of HIV-1 infection: evidence to date. [2020]

2. Italy pubmed.ncbi.nlm.nih.gov

Therapy initiation and rapid start with Bictegravir/Emtricitabine/Tenofovir Alafenamide in PLWH. [2023]

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

Bictegravir/Emtricitabine/Tenofovir Alafenamide for HIV-1: What is the Hidden Potential of This Emerging Treatment? [2023]

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

Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

In vitro evaluation of novel reverse transcriptase inhibitors TAF (tenofovir alafenamide) and OBP-601 (2,3-didehydro-3-deoxy-4-ethynylthymidine) against multi-drug resistant primary isolates of HIV-2. [2021]

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

Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

High resistance barrier to tenofovir alafenamide is driven by higher loading of tenofovir diphosphate into target cells compared to tenofovir disoproxil fumarate. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Update and latest advances in antiretroviral therapy. [2022]