Doravirine for HIV

Recruiting at3 trial locations

Overseen by Theodoros Kelesidis, MD PHD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Antiretrovirals

Must not be taking: CYP3A inducers, CYP3A cleared

Disqualifiers: Pregnancy, Hepatitis, Renal impairment, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing doravirine, an HIV medication, in people with HIV who have abnormal cholesterol levels. The goal is to see if doravirine can help control HIV and improve cholesterol and heart health. Doravirine is a newly-approved antiretroviral.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must be on stable antiretroviral therapy for more than 6 months with specific medications like Genvoya or Biktarvy. You cannot take certain medications that affect liver enzymes, like phenobarbital or rifampin, as they may interfere with the trial drugs.

What data supports the effectiveness of the drug Doravirine for HIV?

Doravirine is effective in treating HIV-1 in adults who have not received prior antiretroviral treatment, showing high efficacy and safety in clinical trials. It is also effective in suppressing the virus in individuals switching to a combination therapy with lamivudine and tenofovir, with rare cases of drug resistance. ^{1 2 3 4 5}

What makes the drug Doravirine unique for treating HIV?

Doravirine is a new type of HIV drug that works by blocking a specific enzyme (reverse transcriptase) the virus needs to multiply. It is unique because it has a better lipid profile compared to some other HIV drugs, meaning it may have fewer effects on cholesterol levels, and it remains effective against certain drug-resistant strains of HIV. ^{1 2 5 6 7}

Research Team

Theodoros Kelesidis, MD PHD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

Adults over 18 with chronic, treated HIV and suppressed viremia for at least 3 months can join. They must have dyslipidemia (abnormal lipids or on lipid-lowering meds) and good kidney function. Participants should be on a stable antiretroviral therapy regimen with Genvoya or Biktarvy for more than six months.

Inclusion Criteria

I am 18 years old or older.

I have been on stable HIV treatment with Genvoya or Biktarvy for over 6 months.

I've been on stable HIV treatment with Genvoya or Biktarvy for over 6 months.

Exclusion Criteria

Anemia precluding safe donation of blood (For men, anemia is typically defined as hemoglobin level of less than 13.5 gram/100 ml and in women as hemoglobin of less than 12.0 gram/100 ml).

I have had a serious heart problem recently.

My kidney function is severely impaired.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Doravirine plus emtricitabine and tenofovir alafenamide fumarate for 3 months

12 weeks

Regular visits as per trial protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Doravirine (Non-nucleoside reverse transcriptase inhibitor)

Trial Overview The trial is testing Doravirine's effects on cholesterol levels and molecular factors linked to heart disease in people with HIV. It compares the switch from an integrase inhibitor-based regimen to one including Doravirine, alongside standard HIV medications TAF/FTC.

Participant Groups

Group I: Doravirine plus emtricitabine and tenofovir alafenamide fumarate Experimental Treatment 1 Intervention

PIFELTRO (doravirine) 100 mg tablet one daily for 3 months Descovy (200 mg emtricitabine + 10 mg tenofovir alafenamide fumarate) tablet one daily for 3 months

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Dr. Thomas Rando

University of California, Los Angeles

Chief Medical Officer since 2023

MD from UCLA

Amir Naiberg

University of California, Los Angeles

Chief Executive Officer since 2024

JD from UCLA

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Doravirine is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for treating HIV-1 infection, available as both a single-agent tablet and a fixed-dose combination with other antiretroviral drugs.

It is specifically indicated for adults with no prior antiretroviral treatment and has received positive regulatory opinions in the USA and EU, highlighting its safety and efficacy for treatment-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine: First Global Approval. Deeks, ED.[2021]

Doravirine shows promise as a treatment option for multidrug-resistant HIV-1, with 23% of cases demonstrating full susceptibility, compared to only 18% for etravirine and 5% for rilpivirine, based on a study of 22 participants with a long history of HIV treatment.

The study found that higher numbers of NNRTI mutations in the virus correlated with increased resistance to doravirine, but doravirine's effectiveness can still be predicted accurately using the Stanford HIVdb algorithm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Residual phenotypic susceptibility to doravirine in multidrug-resistant HIV-1 from subjects enrolled in the PRESTIGIO Registry. Saladini, F., Giammarino, F., Maggiolo, F., et al.[2023]

Doravirine, particularly at a dose of 100 mg, demonstrated the highest efficacy in treating HIV-1 among various treatment options, based on a meta-analysis of six randomized controlled trials.

While doravirine showed a good safety profile, the placebo group had the least adverse events, indicating that doravirine is a safe and well-tolerated option for initial HIV-1 therapy, comparable to other standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of doravirine in treatment-naive HIV-1-infected adults: a systematic review and meta-analysis. Afify, MA., Ahmed, IGG., Alkahtani, TA., et al.[2021]

In a Phase IIb trial involving 342 participants, doravirine 100 mg showed similar effectiveness to efavirenz 600 mg in reducing HIV-1 RNA levels, with 72.9% of doravirine recipients achieving viral suppression compared to 73.1% for efavirenz.

Doravirine was associated with significantly fewer central nervous system adverse events (26.9%) compared to efavirenz (47.2%), indicating a better safety profile for doravirine in this regard.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial. Gatell, JM., Morales-Ramirez, JO., Hagins, DP., et al.[2020]

Doravirine is a safe and effective part of antiretroviral therapy for both treatment-naive and treatment-experienced adults with HIV-1, showing no resistance after 48 weeks in virologically suppressed individuals switching to a regimen including doravirine.

Emergent drug resistance to doravirine is rare (<2%) in treatment-naive patients, and it remains effective against the common K103N resistance mutation, suggesting that resistance to doravirine-based therapies is expected to be uncommon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Pham, HT., Xiao, MA., Principe, MA., et al.[2020]

Doravirine, a new treatment for HIV-1, is taken once daily and shows a favorable pharmacokinetic profile, with no significant impact from age, gender, or mild to moderate renal and hepatic impairments, making it suitable for diverse patient populations.

The drug has a low potential for drug-drug interactions, allowing it to be safely combined with other antiretroviral medications, although it should not be used with strong CYP3A inducers like rifampin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of the Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Doravirine: An Assessment of the Effect of Patient Characteristics and Drug-Drug Interactions. Khalilieh, S., Yee, KL., Sanchez, R., et al.[2023]

References

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

Doravirine: First Global Approval. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Residual phenotypic susceptibility to doravirine in multidrug-resistant HIV-1 from subjects enrolled in the PRESTIGIO Registry. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of doravirine in treatment-naive HIV-1-infected adults: a systematic review and meta-analysis. [2021]

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

Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. [2020]

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

Clinical Pharmacokinetics of the Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Doravirine: An Assessment of the Effect of Patient Characteristics and Drug-Drug Interactions. [2023]