What side effects are associated with this type of intervention?

Common side effects of Doravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), include nausea, fatigue, and headache. In clinical trials, Doravirine was generally well-tolerated with a lower incidence of drug-related adverse events compared to some other antiretroviral drugs. Other NNRTIs may have similar side effects, including rash and liver toxicity. Overall, while Doravirine and similar treatments are effective, patients should be monitored for these potential adverse effects.

What prior FDA approvals exist?

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been a significant class of drugs in the treatment of HIV. Doravirine, a newer NNRTI, is being studied for its potential benefits in patients who have experienced significant weight gain on other regimens. Prior FDA-approved NNRTIs include efavirenz, nevirapine, etravirine, and rilpivirine. These drugs work by inhibiting the reverse transcriptase enzyme, thereby preventing the replication of HIV. Each of these NNRTIs has contributed to the effective management of HIV, often in combination with other antiretroviral agents.

What other types of research exist?

Promising novel alternatives to Doravirine for HIV treatment include the following: 1. Cabotegravir: An integrase strand transfer inhibitor (INSTI) that can be used in combination with rilpivirine for long-acting injectable therapy. 2. Lenacapavir: A capsid inhibitor that has shown potential in clinical trials for its long-acting properties. 3. Islatravir: A nucleoside reverse transcriptase translocation inhibitor (NRTTI) with a unique mechanism of action and promising efficacy and safety profiles. These alternatives offer new mechanisms of action and potential benefits in terms of dosing convenience and resistance profiles.

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Non-nucleoside Reverse Transcriptase Inhibitor

Doravirine for HIV-Associated Weight Gain

Phase 4

Waitlist Available

Research Sponsored by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Eligibility Criteria Checklist

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

Must have

Ability to acquire NRTIs (TAF/FTC or TAF/3TC, and TDF/FTC or TDF/3TC) and INSTI through usual care for the duration of the study

Currently, on a BIC (bictegravir), DTG (dolutegravir), or RAL (raltegravir) +TAF/FTC (or TAF/3TC) regimen with ≥48 weeks INSTI+TAF/FTC (or TAF/3TC) dosing prior to study entry.

Must not have

Historical or current evidence of major mutations associated with any NNRTI resistance

Prior exposure to single-dose nevirapine for the prevention of parent-to-child transmission of HIV

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at day 0, weeks 4, 12, 24, and 48

Awards & highlights

Drug Has Already Been Approved

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing if changing HIV medications to doravirine or switching drug combinations can help patients who have gained weight on their current treatment. The study focuses on people with HIV who have experienced significant weight gain. Doravirine works by blocking a different part of the virus, which might help reduce weight gain and improve overall health. Doravirine is an alternative treatment option for individuals who do not tolerate efavirenz.

Who is the study for?

This trial is for adults with HIV who have experienced significant weight gain after starting an INSTI+TAF/FTC or TAF/3TC regimen. They must have been on this treatment for at least 48 weeks, have a BMI of ≥27.5 kg/m2, and show stable viral suppression with no major mutations associated with drug resistance.

What is being tested?

The study tests if switching to doravirine (a non-nucleoside reverse transcriptase inhibitor) from an INSTI-based regimen can reduce or stabilize weight within a year. It also examines changes in body composition, metabolic health, bone health, and the maintenance of HIV suppression.

What are the potential side effects?

Potential side effects may include typical reactions to antiretroviral therapy such as nausea, headaches, fatigue, possible liver enzyme elevations, and rare but serious risks like lactic acidosis or severe liver problems.

Eligibility Criteria

Inclusion Criteria

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

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I can get the required HIV medications for the study's duration.

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I've been on a specific HIV treatment regimen for at least 48 weeks.

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I have a confirmed HIV-1 diagnosis.

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I gained over 10% of my weight without a clear reason after starting or changing to INSTI-based ART.

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My HIV-1 levels have been undetectable for at least the past year.

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I have confirmed HIV-1 infection.

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I've been on a specific HIV treatment regimen for at least 48 weeks.

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I can get the required HIV medications for the study's duration.

Exclusion Criteria

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

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My tests show major mutations linked to NNRTI resistance.

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I have taken nevirapine once to prevent passing HIV to my child.

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I plan to have weight loss surgery or make major diet or exercise changes soon.

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I have been diagnosed with osteoporosis or osteopenia.

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I haven't been hospitalized or needed serious treatment in the last 30 days.

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My HIV has specific mutations (K65R/E/N or M184V/I).

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at day 0, weeks 4, 12, 24, and 48

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at day 0, weeks 4, 12, 24, and 48

This trial's timeline: 3 weeks for screening, Varies for treatment, and at day 0, weeks 4, 12, 24, and 48 for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Occurrence of Grade ≥3 AEs or >10% reduction in CrCl as estimated by the CKD-EPI equation

Occurrence of confirmed plasma HIV-1 RNA >200 copies/mL

Occurrence of premature discontinuation of study treatment

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Group I: DOR 100 mg + TDF/FTC (or TDF/3TC, depending on location)Experimental Treatment3 Interventions

By mouth daily with or without food

Group II: DOR 100 mg + TAF/FTC (or TAF/3TC, depending on location)Experimental Treatment3 Interventions

By mouth daily with or without food

Group III: Continuation of entry INSTI+TAF/FTC (or TAF/3TC)Experimental Treatment3 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

tenofovir alafenamide/lamivudine

2021

Completed Phase 4

~150

Integrase strand transfer inhibitors

2020

Completed Phase 4

~270

tenofovir disproxil fumarate/emtricitabine

2021

Completed Phase 4

~150

tenofovir disproxil fumarate/lamivudine

2021

Completed Phase 4

~150

Doravirine 100 Mg

2021

Completed Phase 4

~150

Tenofovir alafenamide/emtricitabine

2020

Completed Phase 4

~190

0 / 14Eligibility 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

The most common treatments for HIV infection include non-nucleoside reverse transcriptase inhibitors (NNRTIs) like Doravirine, nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs). NNRTIs, such as Doravirine, work by binding to and inhibiting the reverse transcriptase enzyme, which is crucial for the HIV virus to replicate its genetic material. NRTIs mimic the natural nucleotides used by reverse transcriptase, causing premature termination of the viral DNA chain. PIs inhibit the protease enzyme, preventing the virus from maturing and becoming infectious. INSTIs block the integrase enzyme, which is necessary for the viral DNA to integrate into the host cell's genome. These treatments are vital for HIV patients as they reduce viral load, improve immune function, and decrease the risk of HIV-related complications and transmission.

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.