What is the mechanism of action of this treatment?

The most common treatments for HIV/AIDS include non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase translocation inhibitors (NRTTIs). NNRTIs, such as Doravirine, inhibit the reverse transcriptase enzyme by binding to a specific site, preventing the enzyme from converting viral RNA into DNA, which is essential for HIV replication. NRTTIs, like Islatravir, also target the reverse transcriptase enzyme but work by incorporating themselves into the viral DNA, causing premature termination of the DNA chain. These mechanisms are crucial for HIV/AIDS patients as they significantly reduce the viral load, improve immune function, and decrease the risk of HIV-related complications, thereby enhancing the quality of life and prolonging survival.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of HIV/AIDS, including non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs). NNRTIs like efavirenz, rilpivirine, and etravirine inhibit the reverse transcriptase enzyme, preventing HIV replication. NRTIs such as zidovudine, lamivudine, and tenofovir also target the reverse transcriptase enzyme but through different mechanisms, further inhibiting HIV replication. These drugs form the backbone of antiretroviral therapy (ART) and are often used in combination to enhance efficacy and reduce the risk of resistance. The combination of Doravirine (an NNRTI) and Islatravir (an NRTTI) being studied in the DOR/ISL trial represents a novel approach to HIV treatment by targeting the reverse transcriptase enzyme through complementary mechanisms.

What other types of research exist?

Promising novel alternatives to DOR/ISL for HIV/AIDS treatment in 2024 include long-acting injectable antiretrovirals such as Cabotegravir and Rilpivirine, which offer the convenience of less frequent dosing. Additionally, Lenacapavir, a capsid inhibitor, shows potential due to its unique mechanism of action and long half-life, allowing for biannual dosing. These alternatives provide effective viral suppression with improved adherence and patient convenience.

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Antiretroviral Therapy

DOR/ISL for HIV/AIDS

Q: What side effects are associated with this type of intervention?

Common treatments for HIV/AIDS, particularly those similar to Doravirine/Islatravir (DOR/ISL), can have several side effects. Doravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), may cause rash, liver toxicity, and neuropsychiatric effects such as depression and insomnia. Islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI), may share side effects with other nucleoside reverse transcriptase inhibitors (NRTIs), including gastrointestinal issues, lactic acidosis, and mitochondrial toxicity. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

Phase 3

Waitlist Available

Research Sponsored by Merck Sharp & Dohme LLC

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 102 weeks

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial aims to check if the combination of DOR and ISL is safe and well-tolerated in adults with HIV-1 who have used these drugs before. The study focuses on ensuring that the treatment does not cause harmful side effects in these patients.

Who is the study for?

This trial is for adults with HIV-1 who were previously treated with DOR/ISL in certain Merck Sharp & Dohme clinical studies. It's not open to those who are heavily treatment-experienced from other trials.

What is being tested?

The study is testing the safety and how well people tolerate a combination HIV drug called Doravirine/Islatravir (DOR/ISL). There's no specific hypothesis being tested; it's more about ongoing observation of participants' reactions to the drug.

What are the potential side effects?

While the trial aims to assess safety, potential side effects aren't specified here. Generally, HIV medications can cause issues like nausea, headache, fatigue, and sometimes more serious effects depending on individual health.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 102 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 102 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 102 weeks for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Percentage of Participants with One or More Adverse Event (AE)

Percentage of participants who Discontinue Study Intervention Due to an AE

Secondary study objectives

Percentage of Participants with Evidence of Viral Drug Resistance-Associated Substitutions

Percentage of Participants with HIV-1 RNA <200 copies/mL at Week 96

Percentage of Participants with HIV-1 RNA <50 copies/mL at Week 96

+1 more

Side effects data

From 2024 Phase 3 trial • 672 Patients • NCT04223778

10%

Headache

Accidental overdose

COVID-19

Osteoarthritis

100%

80%

60%

40%

20%

Study treatment Arm

Doravirine/Islatravir (DOR/ISL)

Baseline Background Antiretroviral Therapy (ART)

Awards & Highlights

Pivotal Trial

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

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: DOR/ISLExperimental Treatment1 Intervention

Participants will receive fixed dose combination (FDC) tablet of DOR/ISL (100 mg/0.25 mg) taken once daily (QD) orally from Day 1 to Week 96. After Week 96, eligible participants may continue on DOR/ISL until week 240 or until DOR/ISL becomes commercially accessible, whichever comes first.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

DOR/ISL

2020

Completed Phase 3

~750

Do I qualify?Apply below to find out

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/AIDS include non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase translocation inhibitors (NRTTIs). NNRTIs, such as Doravirine, inhibit the reverse transcriptase enzyme by binding to a specific site, preventing the enzyme from converting viral RNA into DNA, which is essential for HIV replication. NRTTIs, like Islatravir, also target the reverse transcriptase enzyme but work by incorporating themselves into the viral DNA, causing premature termination of the DNA chain. These mechanisms are crucial for HIV/AIDS patients as they significantly reduce the viral load, improve immune function, and decrease the risk of HIV-related complications, thereby enhancing the quality of life and prolonging survival.