Drug information

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Pronounce:
Other Names:
EFdA, ISL, MK-8591
Drug Class:
Nucleoside Reverse Transcriptase Translocation Inhibitors
Molecular Formula:

C12 H12 F N5 O3

Registry Number:
865363-93-5 (CAS)
Chemical Name:

4'-Ethynyl-2-fluoro-2'-deoxyadenosine

Chemical Class:
Purine Nucleosides
Organization:
Merck Sharp & Dohme Corp.
Phase of Development:

Islatravir is in Phase 3 development for HIV treatment. It is being studied as a single-drug capsule and as part of a fixed-dose combination containing doravirine and islatravir (DOR/ISL). Islatravir is also being developed for HIV prevention.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 Treatment Action Group Pipeline Report 2020,3 and ClinicalTrials.gov4,5)

What is islatravir?What is islatravir?

What is islatravir?

Islatravir is an investigational drug that is being studied to treat and prevent HIV infection.4,5

Islatravir belongs to a group of HIV drugs called nucleoside reverse transcriptase translocation inhibitors (NRTTIs). NRTTIs use several different methods to block an HIV enzyme called reverse transcriptase. By blocking reverse transcriptase, NRTTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.6

Islatravir may also be effective against certain HIV strains that are resistant to other HIV drugs.7

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Which clinical trials are studying islatravir?Which clinical trials are studying islatravir?

Which clinical trials are studying islatravir?

Islatravir for HIV treatment

Study Names: MK-8591-011; NCT03272347
Phase: 2b
Status: This study is ongoing, but not recruiting participants.
Locations: Chile, France, United Kingdom, United States
Purpose: The purpose of this trial is to evaluate the safety and effectiveness of three different doses of islatravir in adults with HIV who have never taken HIV medicines before.8

Study Names: MK-8591A-017; NCT04223778
Phase: 3
Status: This study is currently recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of this trial is to evaluate the safety and effectiveness of a switch from a current ART regimen to a fixed-dose combination (FDC) containing doravirine/islatravir.9

Study Names: MK-8591A-018; NCT04223791
Phase: 3
Status: This study is currently recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of this trial is to evaluate the safety and effectiveness of a switch from bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) to an FDC containing doravirine/islatravir.10

Study Names: MK-8591A-019; NCT04233216
Phase: 3
Status: This study is currently recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of this trial is to evaluate the safety and efficacy of islatravir, doravirine, and an FDC containing doravirine/islatravir, each compared to placebo.4

Study Names: MK-8591A-020; NCT04233879
Phase: 3
Status: This study is currently recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of this trial is to evaluate the safety and efficacy of an FDC containing doravirine/islatravir versus Biktarvy in adults with HIV who have never taken HIV medicines before.11

Islatravir for HIV prevention

Study Names: MK-8591-016; NCT04003103
Phase: 2a
Status:This study is currently recruiting participants.
Locations: United States, Israel, South Africa
Purpose: The purpose of this study is to evaluate the safety and pharmacokinetics of two different doses of islatravir given once a month to participants who have a low risk of getting HIV.5

For more details on the studies listed above, see the Health Professional version of this drug summary.

Other studies looking at islatravir for HIV treatment and prevention have been or will be conducted. These include:

  • NCT04295772 : A Phase 2 trial that will evaluate doravirine/islatravir as an HIV treatment in adolescents with viral suppression on ART. See the ClinicalTrials.gov record for this study’s status.12
  • A Phase 1 trial that evaluated the use of an islatravir-based implant to prevent HIV infection.13
What side effects might islatravir cause?What side effects might islatravir cause?

What side effects might islatravir cause?

One goal of HIV research is to identify new drugs that have fewer side effects. In the MK-8591-011 study (NCT03272347) discussed under the previous question, 7.8% of participants who received islatravir reported experiencing a drug-related side effect. Two participants who received the highest dose of islatravir stopped treatment early because of a side effect; one participant experienced diarrhea, nausea, and vomiting, and one participant had an existing hepatitis B virus infection reactivate. The most commonly reported side effects among participants who received any treatment were headache, diarrhea, and nausea. Headache was more common in the combined islatravir groups than in the control arm. Most of the cases of headache were mild, temporary, and unrelated to treatment.8,14

Because islatravir is still being studied, information on possible side effects of the drug is not complete. As testing of islatravir continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying islatravir?Where can I get more information about clinical trials studying islatravir?

Where can I get more information about clinical trials studying islatravir?

More information about islatravir-related research studies is available from ClinicalTrials.gov.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

  1. United States National Library of Medicine. ChemIDplus Advanced: Islatravir. https://chem.nlm.nih.gov/chemidplus/rn/865363-93-5. Accessed August 25, 2020
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed August 25, 2020
  3. Jefferys R. The antiretroviral therapy pipeline 2020. Treatment Action Group Pipeline Report 2020. https://www.treatmentactiongroup.org/wp-content/uploads/2020/07/pipeline_ARV_2020.pdf. Accessed August 25, 2020
  4. Merck Sharp & Dohme Corp. A Phase 3, randomized, clinical study in HIV-1-infected heavily treatment-experienced participants evaluating the antiretroviral activity of blinded islatravir (ISL), doravirine (DOR), and doravirine/islatravir (DOR/ISL), each compared to placebo, and the antiretroviral activity, safety, and tolerability of open-label DOR/ISL. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 15, 2020. NLM Identifier: NCT04233216. https://www.clinicaltrials.gov/ct2/show/NCT04233216. Accessed August 25, 2020
  5. Merck Sharp & Dohme Corp. A Phase 2a, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of oral MK-8591 once-monthly in participants at low-risk for HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 27, 2019. NLM Identifier: NCT04003103. https://clinicaltrials.gov/ct2/show/NCT04003103. Accessed August 25, 2020
  6. Markowitz M, Sarafianos SG. EFdA (4′-ethynyl-2-fluoro-2′-deoxyadenosine, MK-8591): a novel HIV-1 reverse transcriptase translocation inhibitor. Curr Opin HIV AIDS. 2018;13(4):294-299. doi:10.1097/COH.0000000000000467
  7. Grobler J. Efficacy of MK-8591 against diverse HIV-1 subtypes and NRTI-resistant clinical isolates. Webcast presented at: International Congress of Drug Therapy in HIV Infection (HIV Glasgow); October 28-31, 2018; Glasgow, United Kingdom. https://vimeo.com/298576925. Accessed August 25, 2020
  8. Merck Sharp & Dohme Corp. A Phase 2B, randomized, double-blind, active-comparator-controlled, dose-ranging clinical trial to evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of MK-8591 given in combination with doravirine (DOR) and lamivudine (3TC) in HIV-1-infected treatment-naive adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 1, 2017. NLM Identifier: NCT03272347. https://clinicaltrials.gov/ct2/show/NCT03272347. Accessed August 25, 2020
  9. Merck Sharp & Dohme Corp. A Phase 3 randomized, active-controlled, open-label clinical study to evaluate a switch to doravirine/islatravir (DOR/ISL) once-daily in participants with HIV-1 virologically suppressed on antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 8, 2020. NLM Identifier: NCT04223778. https://www.clinicaltrials.gov/ct2/show/record/NCT04223778. Accessed August 25, 2020
  10. Merck Sharp & Dohme Corp. A Phase 3, randomized, active-controlled, double-blind clinical study to evaluate a switch to doravirine/islatravir (DOR/ISL) once-daily in participants with HIV- 1 virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 8, 2020. NLM Identifier: NCT04223791. https://www.clinicaltrials.gov/ct2/show/NCT04223791. Accessed August 25, 2020
  11. Merck Sharp & Dohme Corp. A Phase 3 randomized, active-controlled, double-blind clinical study to evaluate the antiretroviral activity, safety, and tolerability of doravirine/islatravir once-daily in HIV-1 infected treatment-naïve participants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 15, 2020. NLM Identifier: NCT04233879. https://www.clinicaltrials.gov/ct2/show/NCT04233879. Accessed August 25, 2020
  12. Merck Sharp & Dohme Corp. A Phase 2 clinical study to evaluate the pharmacokinetics, safety, and efficacy of doravirine/islatravir in adolescents with HIV-1 infection who are virologically suppressed, are ≥12 to <18 years of age, and weigh ≥35 kg. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 3, 2020. NLM Identifier: NCT04295772. https://www.clinicaltrials.gov/ct2/show/NCT04295772. Accessed August 25, 2020
  13. Matthews RP, Barrett SE, Patel M, et al. First-in-human trial of MK-8591-eluting implants demonstrates concentrations suitable for HIV prophylaxis for at least one year. Abstract presented at: IAS Conference on HIV Science; July 21-24, 2019; Mexico City, Mexico. Abstract TUAC0401LB. http://programme.ias2019.org/Abstract/Abstract/4843. Accessed August 25, 2020
  14. DeJesus E, Molina J-M, Yazdanpanah Y, et al. Islatravir (ISL, MK-8591) safety analysis through Week 48 from a Phase 2 trial in treatment naive adults with HIV-1 infection. Slides presented at: International AIDS Conference; July 6-10, 2020. https://go.aws/2Ak3eKp. Accessed August 25, 2020

Last Reviewed: August 25, 2020