What side effects are associated with this type of intervention?

Common treatments for HIV, particularly those similar to Doravirine (an NNRTI), include side effects such as diarrhea, nausea, headache, and upper respiratory tract infections. Doravirine is noted for potentially reducing metabolic and cardiovascular toxicities associated with ART. Other ART regimens, like ritonavir-boosted darunavir, have higher incidences of gastrointestinal issues. Tenofovir and emtricitabine, often used with NNRTIs, are generally well-tolerated but can cause renal and bone toxicities. Integrase inhibitors, another class of ART, may lead to weight gain and neuropsychiatric effects. While effective, ART side effects vary by drug class and individual agents.

What prior FDA approvals exist?

The FDA has approved several Non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of HIV, similar to Doravirine. These include efavirenz, nevirapine, and rilpivirine. NNRTIs work by inhibiting the reverse transcriptase enzyme, which is crucial for viral replication. Doravirine, in particular, is being studied for its potential to reduce ART-related metabolic and cardiovascular toxicities, making it a promising option for minimizing long-term side effects. Other related drugs include integrase inhibitors like dolutegravir and protease inhibitors such as ritonavir-boosted darunavir, which are often used in combination with NNRTIs or NRTIs to enhance treatment efficacy.

What other types of research exist?

Promising alternatives to Doravirine for HIV patients include newer NNRTIs like Rilpivirine and Etravirine, which have shown favorable safety profiles. Additionally, integrase strand transfer inhibitors (INSTIs) such as Bictegravir and Dolutegravir are considered effective with potentially lower metabolic and cardiovascular risks. These options should be discussed with a healthcare provider to tailor the best treatment plan for individual patients.

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Non-nucleoside reverse transcriptase inhibitor

Doravirine for HIV

Q: What is the mechanism of action of this treatment?

Common treatments for HIV include several classes of antiretroviral drugs, each targeting different stages of the HIV life cycle. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), like Doravirine, bind to and inhibit the reverse transcriptase enzyme, preventing the conversion of viral RNA into DNA, which is crucial for viral replication. Nucleoside reverse transcriptase inhibitors (NRTIs) mimic natural nucleotides and get incorporated into the viral DNA, causing chain termination. Protease inhibitors (PIs) block the protease enzyme, preventing the maturation of viral particles. Integrase inhibitors (INIs) prevent the integration of viral DNA into the host genome. These treatments are vital for HIV patients as they reduce viral load, improve immune function, and decrease the risk of HIV-related complications. Specifically, NNRTIs like Doravirine are being studied for their potential to minimize metabolic and cardiovascular toxicities associated with ART, which is significant for improving long-term health outcomes in HIV patients.

Phase < 1

Recruiting

Led By Theodoros Kelesidis, MD PHD

Research Sponsored by University of Texas Southwestern Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

18 years of age or older

On stable antiretroviral therapy for >6 months with Genvoya (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg; E/C/F/TAF) 2) Biktarvy (bictegravir 50 mg/ emtricitabine 200 mg/tenofovir alafenamide 25 mg; B/F/TAF)

Must not have

History of severe or recent cardiac event

History of severe renal impairment (eGFR < 30 ml/min/1.73 m2)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 weeks post switch of antivirals

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Doravirine may cause side effects like rash, nausea, diarrhea, headache, fatigue, abnormal dreams, insomnia and changes in liver enzymes. Side effects vary by individual.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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

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

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My kidneys are working well, as shown by tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a serious heart problem recently.

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My kidney function is severely impaired.

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I am not taking medications like phenobarbital, phenytoin, carbamazepine, or rifampin.

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I am not taking medications like Cisapride or Lovastatin that are cleared by CYP3A.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 weeks post switch of antivirals

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 weeks post switch of antivirals

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 weeks post switch of antivirals for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

HDL function

Monocyte chemotaxis

Monocyte derived foam cell formation of monocytes

Secondary study objectives

Total cholesterol

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Doravirine plus emtricitabine and tenofovir alafenamide fumarateExperimental Treatment1 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

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for HIV include several classes of antiretroviral drugs, each targeting different stages of the HIV life cycle. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), like Doravirine, bind to and inhibit the reverse transcriptase enzyme, preventing the conversion of viral RNA into DNA, which is crucial for viral replication. Nucleoside reverse transcriptase inhibitors (NRTIs) mimic natural nucleotides and get incorporated into the viral DNA, causing chain termination. Protease inhibitors (PIs) block the protease enzyme, preventing the maturation of viral particles. Integrase inhibitors (INIs) prevent the integration of viral DNA into the host genome. These treatments are vital for HIV patients as they reduce viral load, improve immune function, and decrease the risk of HIV-related complications. Specifically, NNRTIs like Doravirine are being studied for their potential to minimize metabolic and cardiovascular toxicities associated with ART, which is significant for improving long-term health outcomes in HIV patients.

Zidovudine response relationships in early human immunodeficiency virus infection.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.The Chronicity of HIV Infection Should Drive the Research Strategy of NeuroHIV Treatment Studies: A Critical Review.