Drug information

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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 developed as a stand-alone agent and as part of a fixed-dose combination containing doravirine and islatravir (DOR/ISL).  Islatravir is also in Phase 3 development for HIV prevention.

Chemical Image: (Click to enlarge)

Islatravir

Molecular Weight: 293.2568

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and Treatment Action Group Pipeline Report 20213,4)

Pharmacology

Pharmacology

Mechanism of Action: Nucleoside reverse transcriptase translocation inhibitor (NRTTI). Islatravir (ISL), a deoxyadenosine analog, belongs to a new class of ARV drugs called NRTTIs. It has potent activity against HIV-1 and is also active against HIV-2 and multidrug-resistant HIV strains.5,6

Intracellularly, ISL is converted to its active triphosphate form (ISL-TP). ISL-TP inhibits HIV reverse transcriptase (RT) through multiple modes of action. Primarily, ISL-TP functions as an immediate chain terminator—after ISL is incorporated into viral DNA, it blocks RT translocation and prevents nucleotide attachment onto the viral DNA chain. In instances where RT translocation does occur and additional nucleotides are allowed to incorporate onto the viral DNA chain, ISL-TP can act as a delayed chain terminator by causing structural changes to the viral chain. Furthermore, ISL can be misincorporated by RT, resulting in mismatched primers that cannot be extended or excised.5-8

Half-life (T½): In a multiple-dose study of oral ISL (0.25, 0.75, and 5 mg) in healthy adults without HIV, the apparent terminal half-life of ISL in plasma increased with dose, ranging from 86.9 to 230 hours. The apparent terminal half-life of ISL-TP was 177 to 209 hours.9

In a Phase 1b trial (NCT02217904) evaluating single oral doses of ISL (0.5 to 30 mg) in treatment-naive adults, the intracellular half-life of ISL-TP ranged from 78.5 to 128 hours.10

Metabolism/Elimination: In vitro studies indicate that ISL undergoes adenosine deaminase-mediated metabolism and renal excretion; hepatic metabolism, however, does not appear to have a significant role in ISL elimination.11

Resistance: A Phase 2b trial (NCT03272347) evaluated three doses of ISL that were administered in combination with doravirine (DOR) in treatment-naive individuals. By Week 48, five participants who received ISL plus DOR had experienced protocol-defined virologic failure; however, all of these participants had HIV-1 RNA <80 copies/mL, and none met the criteria for resistance testing.12 No participants met the criteria for resistance testing through Week 144 of the trial.13

Select Clinical Trials

Select Clinical Trials

On December 13, 2021, the U.S. FDA placed clinical holds on studies of islatravir for HIV treatment and prevention. The FDA’s decision was based on reports of decreases in total lymphocyte and CD4 counts in some participants receiving islatravir in trials.

Participants who started treatment in ongoing studies of DOR/ISL will continue receiving study drugs; however, no new participants will be screened or randomized in DOR/ISL studies. Participants receiving ISL in prevention studies will no longer receive study drug; however, their CD4 and lymphocyte counts will continue to be monitored. For more information about the clinical holds on trials evaluating islatravir, please refer to the drug developer’s December 13, 2021 press release.14


Islatravir for HIV treatment

Study Identifiers: MK-8591-011; NCT03272347
Sponsor: Merck Sharp & Dohme Corp.
Phase: 2b
Status: This study was placed on partial clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this trial is to evaluate the safety and efficacy of a regimen that consists of ISL (at three different dose levels) plus DOR and 3TC over 24 weeks in treatment-naive participants. After 24 weeks, investigators will evaluate the safety and efficacy of ISL (at three different dose levels) plus DOR. In both cases, the active comparator group will receive DOR/3TC/TDF.
Study Population:

  • Participants are treatment-naive adults with HIV.
  • Participants have HIV RNA ≥1,000 copies/mL and CD4 counts ≥200 cells/mm3.
  • Participants have no known resistance to any approved NRTI, NNRTI, PI, INSTI, or any study drug.14-16

Selected Study Results:


Study Identifiers: IMAGINE-DR; MK-8591-013; NCT04564547
Sponsor: Merck Sharp & Dohme Corp.
Phase: 2b
Status: See note below. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this study is to evaluate a switch to ISL plus the investigational NNRTI MK-8507 given once weekly in participants who are virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy).
Study Population:

  • Participants are adults with HIV who have been virologically suppressed on Biktarvy for at least 6 months.
  • Participants have HIV RNA <50 copies/mL and CD4 counts >200 cells/mm3 at screening.17,18

Note: The developers of islatravir announced in a November 18, 2021 press release that they were stopping dosing of participants in the MK-8591-013 trial. This decision was based on findings of reduced total lymphocyte and CD4 counts in study participants receiving ISL and MK-8507.18 As of December 1, 2021, all participants have discontinued study treatment and will be switched to non-study ARV therapy. Participants who received ISL and MK-8507 will be followed for at least 6 months.17


Study Identifiers: GS-US-563-6041; NCT05052996
Sponsor: Gilead Sciences
Phase: 2
Status: See note below. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this open-label study is to evaluate the efficacy of oral weekly ISL in combination with the investigational capsid inhibitor lenacapavir in participants who are virologically suppressed on Biktarvy.
Study Population:

  • Participants are adults with HIV who have been virologically suppressed on Biktarvy for at least 24 weeks before and at screening.19

Note: The developers of islatravir and lenacapavir announced in a December 13, 2021 press release that they were stopping dosing of participants in the GS-US-563-6041 trial. Participants will discontinue study treatment and will restart their prior ARV regimen.14


Study Identifiers: ILLUMINATE SWITCH A; MK-8591A-017; NCT04223778
Sponsor: Merck Sharp & Dohme Corp.
Phase: 3
Status: This study was placed on partial clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this open-label trial is to evaluate the safety and efficacy of a switch from a current ART regimen to a fixed-dose combination (FDC) containing DOR/ISL.
Study Population:

  • Participants are adults with HIV who have been receiving a continuous, stable 2- or 3-drug ART regimen for at least the past 3 months.
  • Participants have had viral suppression on ART with HIV RNA <50 copies/mL for at least the past 3 months.
  • Participants have no history of virologic treatment failure on any past or current ART regimen.14,20

Selected Study Results:


Study Identifiers: ILLUMINATE SWITCH B; MK-8591A-018; NCT04223791
Sponsor: Merck Sharp & Dohme Corp.
Phase: 3
Status: This study was placed on partial clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this trial is to evaluate the safety and efficacy of a switch from Biktarvy to an FDC containing DOR/ISL.
Study Population:

  • Participants are adults with HIV who have been receiving Biktarvy for at least the past 3 months.
  • Participants have had viral suppression on Biktarvy with HIV RNA <50 copies/mL for at least the past 3 months.
  • Participants have no history of virologic treatment failure on any past or current ART regimen.14,21

Selected Study Results:


Study Identifiers: ILLUMINATE HTE; MK-8591A-019; NCT04233216
Sponsor: Merck Sharp & Dohme Corp.
Phase: 3
Status: This study was placed on partial clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this trial is to evaluate the safety and efficacy of ISL, DOR, and an FDC containing DOR/ISL, each compared to placebo, in heavily treatment-experienced participants.
Study Population:

  • Participants are heavily treatment–experienced children and adults with HIV who have been receiving the same ART regimen for at least the past 3 months.
  • Participants have resistance to at least one drug within three different ARV drug classes (NRTI, NNRTI, and either PI or INSTI) and have limited treatment options available to form a viable ART regimen.14,22


Study Identifiers: ILLUMINATE NAIVE; MK-8591A-020; NCT04233879
Sponsor: Merck Sharp & Dohme Corp.
Phase: 3
Status: This study was placed on partial clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this trial is to evaluate the safety and efficacy of an FDC containing DOR/ISL versus Biktarvy in treatment-naive participants.
Study Population:

  • Participants are treatment-naive adults with HIV.
  • Participants have no known resistance to any approved HIV-1 reverse transcriptase inhibitor or any study intervention.14,23


Additional trials evaluating DOR/ISL for HIV treatment are being conducted, including:

  • ILLUMINATE YOUTH (MK-8591A-028; NCT04295772): A Phase 2 open-label study evaluating DOR/ISL as an HIV treatment in pediatric participants (less than 18 years of age and weighing at least 35 kg) who are virologically suppressed on ART or treatment-naive. This study was placed on partial clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.14,24
  • MK-8591A-033 (NCT04776252): A Phase 3 open-label rollover study evaluating the safety of DOR/ISL in adult and pediatric participants who received DOR/ISL in a previous clinical trial. This study was placed on partial clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.14,25


Islatravir for HIV prevention

Study Identifiers: MK-8591-016; NCT04003103
Sponsor: Merck Sharp & Dohme Corp.
Phase: 2a
Status: This study was placed on full clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of two different doses of oral ISL administered once monthly to participants who are at low risk of acquiring HIV.
Study Population:

  • Participants are adults without HIV who are at low risk of acquiring HIV.14,26

Selected Study Results:


Study Identifiers: MK-8591-043; NCT05115838
Sponsor: Merck Sharp & Dohme Corp.
Phase: 2a
Status: This study was placed on full clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of different doses of a once-yearly ISL implant in participants who are at low risk of acquiring HIV.
Study Population:

  • Participants are adults without HIV who are at low risk of acquiring HIV.14,27


Study Identifiers: MK-8591-035; NCT05130086
Sponsor: Merck Sharp & Dohme Corp.
Phase: 2
Status: This study was placed on full clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this open-label study is to evaluate the safety and tolerability of oral ISL administered once monthly in trans and gender diverse participants who are receiving gender-affirming hormone therapy and are at low risk of acquiring HIV.
Study Population:

  • Participants are adults without HIV who are on stable gender-affirming hormone therapy and who do not intend to change therapy through Week 4 of the study.
  • Participants are individuals who identify with a gender that is different from that assigned at birth.
  • Participants are at low risk of acquiring HIV.14,28


Study Identifiers: IMPOWER 22; MK-8591-022; NCT04644029
Sponsor: Merck Sharp & Dohme Corp.
Phase: 3
Status: This study was placed on full clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this study is to evaluate the safety and efficacy of oral ISL administered once monthly as PrEP in cisgender women who are at high risk of acquiring HIV.
Study Population:

  • Participants are cisgender women without HIV who are at least 16 years of age and older.
  • Participants have been sexually active with a male partner in the past 30 days before screening and are at high risk of acquiring HIV.14,29


Study Identifiers: IMPOWER 24; MK-8591-024; NCT04652700
Sponsor: Merck Sharp & Dohme Corp.
Phase: 3
Status: This study was placed on full clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.
Study Purpose: The purpose of this study is to evaluate the safety and efficacy of oral ISL administered once monthly as PrEP in cisgender men who have sex with men and transgender women who have sex with men and who are at high risk of acquiring HIV.
Study Population:

  • Participants are cisgender men who have sex with men and transgender women who have sex with men without HIV and who are at least 16 years of age and older.
  • Participants have been sexually active with male or transgender women partners in the past month before screening and are at high risk of acquiring HIV.14,30


Additionally, an injectable formulation of ISL is being evaluated in a Phase 1 trial (MK-8591-034). This study was placed on full clinical hold in December 2021. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on this study’s status.14

Adverse Events

Adverse Events

On December 13, 2021, the FDA placed clinical holds on studies of islatravir for HIV treatment and prevention. The FDA’s decision was based on safety concerns over decreases in total lymphocyte and CD4 counts in some participants receiving islatravir in trials. For more information about the clinical holds on trials evaluating islatravir, please refer to the drug developer’s December 13, 2021 press release.14

MK-8591-011 (NCT03272347)

In this Phase 2b study, 90 participants received ISL (in doses of 0.25 mg, 0.75 mg, or 2.25 mg) plus DOR and 3TC and 31 participants received DOR/3TC/TDF for 24 weeks (Part 1). After 24 weeks, eligible participants who were receiving ISL, DOR, and 3TC switched to a two-drug regimen of ISL plus DOR (Part 2). The Week 48 analysis found that 73% of participants who received any dose of ISL and 77% of participants who received DOR/3TC/TDF experienced at least one adverse event (AE). Drug-related AEs occurred in 8% of participants who received ISL and 19% of participants who received DOR/3TC/TDF. No serious drug-related AEs were reported with ISL. Two participants who received the 2.25-mg dose of ISL discontinued treatment because of an AE; one participant experienced diarrhea, nausea, and vomiting, and one participant had HBV reactivation. Headache was more common in the combined ISL groups (11%) than in the DOR/3TC/TDF group (6%), and diarrhea was more common in the DOR/3TC/TDF group (16%) than in the combined ISL groups (7%). Most of the cases of headache and diarrhea were mild, transient, and unrelated to treatment.15,16

Results through Week 144 of the MK-8591-011 study include data from the open-label maintenance phase of the trial where all participants in the ISL plus DOR groups transitioned to the selected ISL dose of 0.75 mg plus DOR 100 mg (Part 3). The rate of drug-related AEs continued to be lower in the ISL groups (7.8%) than in the DOR/3TC/TDF group (22.6%). There were no additional participants who discontinued treatment because of an AE.13

ILLUMINATE SWITCH A (MK-8591A-017; NCT04223778) and ILLUMINATE SWITCH B (MK-8591A-018; NCT04223791)

Week 48 primary endpoint results for two Phase 3 trials evaluating the DOR/ISL FDC in participants who were virologically suppressed on different ART regimens or Biktarvy were released in a company press release. In both trials, DOR/ISL exhibited a safety profile that was similar to what has already been seen in Phase 2 studies.20,21,31

MK-8591-016 (NCT04003103)

In this Phase 2a trial evaluating ISL for PrEP, participants were randomized to once monthly oral doses of ISL 60 mg (n = 97), ISL 120 mg (n = 97), or placebo (n = 48). Results through Week 24 showed that approximately 60% of participants in each of the ISL groups and 67% of participants in the placebo group experienced at least one AE. The majority of AEs were mild in intensity, with the most common AEs overall being headache, diarrhea, and nausea. Drug-related AEs, all of which were mild or moderate, occurred in 9.3% of participants in the ISL 60 mg group, 15.5% of participants in the ISL 120 mg group, and 25% of participants in the placebo group. Two participants discontinued study drug because of an AE — one due to a mild foreign body sensation in the throat and one due to moderate rash and pruritus. Grade 3-4 laboratory abnormalities were uncommon.26,32

Drug Interactions

Drug Interactions

In vitro, ISL does not interact with renal or hepatic drug transporters or major enzymes involved in drug metabolism, including CYP enzymes and UGT1A1.11,33 Although ISL was shown to be a substrate of BCRP in vitro, this finding is unlikely to be clinically significant.11

During a drug-drug interaction study in adults who did not have HIV, the coadministration of ISL and DOR did not affect the pharmacokinetics of either drug.34 In addition, a two-way interaction study in participants who did not have HIV found that ISL does not appear to have any significant pharmacokinetic interaction with dolutegravir plus TDF.35

The pharmacokinetics of levonorgestrel (LNG) and ethinyl estradiol (EE) were not affected when an oral contraceptive that contained these drugs was coadministered with ISL. This suggests that hormonal contraceptives that contain LNG or EE can be used in individuals who are taking ISL.36

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: Islatravir. https://chem.nlm.nih.gov/chemidplus/rn/865363-93-5. Accessed January 5, 2022
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed January 5, 2022
  3. Jefferys R. The antiretroviral therapy pipeline 2021. Treatment Action Group Pipeline Report 2021. https://www.treatmentactiongroup.org/wp-content/uploads/2021/07/pipeline_2021_hiv_ARV_final.pdf. Accessed January 5, 2022
  4. Jefferys R. The PrEP and microbicides pipeline. Treatment Action Group Pipeline Report 2021. https://www.treatmentactiongroup.org/wp-content/uploads/2021/07/pipeline_2021_hiv_PrEP_final.pdf. Accessed January 5, 2022
  5. Michailidis E, Huber AD, Ryan EM, et al. 4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) Inhibits HIV-1 Reverse Transcriptase with Multiple Mechanisms. J Biol Chem. 2014;289(35):24533-24548. doi:10.1074/jbc.M114.562694
  6. 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 January 5, 2022
  7. Michailidis E, Marchand B, Kodama EN, et al. Mechanism of inhibition of HIV-1 reverse transcriptase by 4′-ethynyl-2-fluoro-2′-deoxyadenosine triphosphate, a translocation-defective reverse transcriptase inhibitor. J Biol Chem. 2009;284(51):35681-35691. doi:10.1074/jbc.M109.036616
  8. 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
  9. Matthews RP, Jackson Rudd D, Zhang S, et al. Safety and pharmacokinetics of once-daily multiple-dose administration of islatravir in adults without HIV. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2021;88(3):314-321. doi:10.1097/QAI.0000000000002755
  10. Schürmann D, Rudd DJ, Zhang S, et al. Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial. Lancet HIV. 2020;7(3):e164-e172. doi:10.1016/S2352-3018(19)30372-8
  11. Bleasby K, Houle R, Hafey M, et al. Islatravir is not expected to be a victim or perpetrator of drug-drug interactions via major drug-metabolizing enzymes or transporters. Viruses. 2021;13(8):1566. doi:10.3390/v13081566
  12. Molina JM, Yazdanpanah Y, Afani Saud A, et al. Islatravir (ISL, MK-8591) at doses of 0.25 to 2.25 mg QD, in combination with doravirine maintains viral suppression through 48 weeks in adults with HIV-1 infection. Slides presented at: IAS Conference on HIV Science; July 21-24, 2019; Mexico City, Mexico. https://programme.ias2019.org/PAGMaterial/PPT/1878_4152/2019 IAS Presentation Molina MK-8591-011 48 wk FINAL 7-24-19 LOCKED.pptx. Accessed January 5, 2022
  13. Molina J-M, Yazdanpanah Y, Afani A, et al. Efficacy and safety of islatravir in combination with doravirine through 144 weeks for treatment-naïve adults with HIV-1 infection in a Phase 2b trial. European AIDS Conference; October 27-30, 2021; Virtual and United Kingdom. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2021. https://www.natap.org/2021/EACS/EACS_21.htm. Accessed January 5, 2022
  14. Merck: Press release, dated December 13, 2021. Merck announces clinical holds on studies evaluating islatravir for the treatment and prevention of HIV-1 infection. https://www.merck.com/news/merck-announces-clinical-holds-on-studies-evaluating-islatravir-for-the-treatment-and-prevention-of-hiv-1-infection/. Accessed January 5, 2022
  15. 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-naïve 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 January 5, 2022
  16. Molina JM, Yazdanpanah Y, Afani Saud A, et al. Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir, doravirine, and lamivudine: a phase 2b, randomised, double-blind, dose-ranging trial. The Lancet HIV. 2021;8(6):e324-e333. doi:10.1016/S2352-3018(21)00021-7
  17. Merck Sharp & Dohme Corp. A Phase 2b, randomized, active-controlled, double-blind, dose-ranging clinical study to evaluate a switch to islatravir (ISL) and MK-8507 once-weekly in adults with HIV-1 virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 21, 2020. NLM Identifier: NCT04564547. https://clinicaltrials.gov/ct2/show/NCT04564547. Accessed January 5, 2022
  18. Merck: Press release, dated November 18, 2021. Merck provides update on Phase 2 clinical trial of once-weekly investigational combination of MK-8507 and islatravir for the treatment of people living with HIV-1. https://www.merck.com/news/merck-provides-update-on-phase-2-clinical-trial-of-once-weekly-investigational-combination-of-mk-8507-and-islatravir-for-the-treatment-of-people-living-with-hiv-1/. Accessed January 5, 2022
  19. Gilead Sciences. A Phase 2 randomized, open-label, active-controlled study evaluating the safety and efficacy of an oral weekly regimen of islatravir in combination with lenacapavir in virologically suppressed people with HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 13, 2021. NLM Identifier: NCT05052996. https://clinicaltrials.gov/ct2/show/NCT05052996. Accessed January 5, 2022
  20. 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://clinicaltrials.gov/ct2/show/study/NCT04223778. Accessed January 5, 2022
  21. 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://clinicaltrials.gov/ct2/show/NCT04223791. Accessed January 5, 2022
  22. 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://clinicaltrials.gov/ct2/show/NCT04233216. Accessed January 5, 2022
  23. 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://clinicaltrials.gov/ct2/show/NCT04233879. Accessed January 5, 2022
  24. Merck Sharp & Dohme Corp. A Phase 2 clinical study to evaluate the pharmacokinetics, safety, and efficacy of doravirine/islatravir in pediatric participants with HIV-1 infection who are virologically suppressed or treatment-naïve, are less than 18 years of age, and weigh greater than or equal to 35 kg. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 3, 2020. NLM Identifier: NCT04295772. https://clinicaltrials.gov/ct2/show/NCT04295772. Accessed January 5, 2022
  25. Merck Sharp & Dohme Corp. A Phase 3 open-label rollover clinical study of doravirine/islatravir (DOR/ISL) once-daily for the treatment of HIV-1 infection in participants who previously received DOR/ISL in a Phase 2 or Phase 3 DOR/ISL clinical study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 26, 2021. NLM Identifier: NCT04776252. https://clinicaltrials.gov/ct2/show/NCT04776252. Accessed January 5, 2022
  26. 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 January 5, 2022
  27. Merck Sharp & Dohme Corp. A Phase 2a, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of a radiopaque matrix MK-8591 implant in participants at low-risk for HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 2, 2021. NLM Identifier: NCT05115838. https://clinicaltrials.gov/ct2/show/NCT05115838. Accessed January 5, 2022
  28. Merck Sharp & Dohme Corp. A Phase 2 open-label study to evaluate the safety and pharmacokinetics of oral islatravir once-monthly in trans and gender diverse individuals on gender-affirming hormone therapy and at low-risk for HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2021. NLM Identifier: NCT05130086. https://clinicaltrials.gov/ct2/show/NCT05130086. Accessed January 5, 2022
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Last Reviewed: January 5, 2022