Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016)
CompletedPhase 2Results postedLast updated 18 July 2025
What this trial tests
Phase 2 trial testing Islatravir in HIV-1 Infection in 242 participants. Completed in 24 November 2022.
Adults 18 to 65, any sex, with HIV-1 Infection. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Number of Participants With ≥1 Adverse Event (AE) Through Week 36Primary· Up to 36 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Group
Value
95% CI
Islatravir 60 mg
66
Islatravir 120 mg
63
Placebo
36
Number of Participants Discontinuing From Study Therapy Due to AEPrimary· Up to 20 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Group
Value
95% CI
Islatravir 60 mg
1
Islatravir 120 mg
1
Placebo
0
Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AEPrimary· Up to 20 weeks
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study therapy.
Group
Value
95% CI
Islatravir 60 mg
1
Islatravir 120 mg
1
Placebo
0
Number of Participants With ≥1 Drug-related AE Through Week 36Primary· Up to 36 weeks
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.
Group
Value
95% CI
Islatravir 60 mg
9
Islatravir 120 mg
14
Placebo
12
Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36Primary· Up to 36 weeks
An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.
Group
Value
95% CI
Islatravir 60 mg
1
Islatravir 120 mg
0
Placebo
0
Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36Primary· Up to 36 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').
Group
Value
95% CI
Islatravir 60 mg
5
Islatravir 120 mg
4
Placebo
1
Number of Participants With ≥1 Drug-related SAE Through Week 36Primary· Up to 36 weeks
An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.
Group
Value
95% CI
Islatravir 60 mg
0
Islatravir 120 mg
0
Placebo
0
Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36Primary· Up to 36 weeks
A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).
Group
Value
95% CI
Islatravir 60 mg
0
Islatravir 120 mg
0
Placebo
0
Number of Participants With an AE Resulting in Death Through Week 36Primary· Up to 36 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Group
Value
95% CI
Islatravir 60 mg
0
Islatravir 120 mg
0
Placebo
0
Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISLSecondary· Day 1 and Day 140: predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit.
The AUC0-672 of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
Day 1
Group
Value
95% CI
Islatravir 60 mg
7.88
± 56.8
Islatravir 120 mg
16.6
± 50.5
Day 140
Group
Value
95% CI
Islatravir 60 mg
21.2
± 140.3
Islatravir 120 mg
37.6
± 136.6
Maximum Plasma Concentration (Cmax) of ISLSecondary· Day 1 and Week 20, collect predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit.
The Cmax of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
Day 1
Group
Value
95% CI
Islatravir 60 mg
0.387
± 279.9
Islatravir 120 mg
0.954
± 186.2
Day 140
Group
Value
95% CI
Islatravir 60 mg
0.376
± 597.7
Islatravir 120 mg
0.792
± 349.6
Trough Plasma Concentration (Ctrough) of ISLSecondary· Day 1 and Week 20: predose and 30-min postdose. Day 2: 24 hours post Day 1 dose. Weeks 1, 2, 3, 21, 22, 23 and 24: any time during the study visit. Weeks 4, 8, 12 and 16: predose.
The plasma Ctrough of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
Day 1
Group
Value
95% CI
Islatravir 60 mg
0.000556
± 36.6
Islatravir 120 mg
0.00101
± 37.0
Day 140
Group
Value
95% CI
Islatravir 60 mg
0.000809
± 37.0
Islatravir 120 mg
0.000124
± 42.0
Adverse events — posted to ClinicalTrials.gov
Time frame: Up to 36 weeks.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
This study will evaluate the safety, tolerability and pharmacokinetics (PK) of 6 once-monthly doses of oral islatravir (60 mg and 120 mg) compared with placebo in adults at low risk of HIV-1 infection
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT06719570 — A Study of Doravirine and Islatravir as a Single Entity or Combination Therapy and the Effect of Food in Healthy Adult P
· Phase 1
· completed
NCT06619678 — A Study of MK-8507 and Islatravir (MK-8591) in Healthy Adult Participants (MK-8507-016)
· Phase 1
· completed
NCT05115838 — Radiopaque Matrix MK-8591 Implant in Participants at Low-Risk for Human Immunodeficiency Virus Type 1 (HIV-1) Infection
· Phase 2
· withdrawn
NCT05130086 — A Study of Islatravir (MK-8591) in Trans and Gender Diverse Participants (MK-8591-035)
· Phase 2
· withdrawn
NCT04564547 — Dose Ranging, Switch Study of Islatravir (MK-8591) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adu
· Phase 2
· completed
Other recruiting trials for HIV-1 Infection
Currently open trials in the same condition.
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· recruiting
NCT05705349 — DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053)
· Phase 3
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NCT05631093 — A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Vir
· Phase 3
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NCT05630755 — A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Vir
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Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Merck Sharp & Dohme LLC
Last refreshed: 18 July 2025
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04003103.