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HIV-1 InfectionPhase 2NCT05052996

Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV

A Phase 2 study testing ISL, LEN and B/F/TAF in people with HIV-1 Infection, run by Gilead Sciences at 44 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The primary objective of this study is to evaluate the efficacy of oral weekly islatravir (ISL) in combination with lenacapavir (LEN) in virologically suppressed people with HIV (PWH) at Week 24. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1 Infection
What is being tested?
ISL, LEN and B/F/TAF
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
142 participants
Where
44 sitesUnited States
Study dates
5 Oct 2021to Mar 2028
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for ≥ 24 weeks at screening.
  • Documented plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 24 weeks before and at screening.
  • Plasma HIV-1 RNA < 50 copies/mL at screening.

Who cannot join

  • History of prior virologic failure while receiving treatment for HIV-1.
  • Prior use of, or exposure to, islatravir (ISL) or lenacapavir (LEN).
  • Active, serious infections requiring parenteral therapy < 30 days before randomization.
  • Active or occult hepatitis B virus (HBV) coinfection, defined as hepatitis B core antibody (HBcAb) positive, hepatitis B surface antigen (HBsAg) positive, or HBV deoxyribonucleic acid (DNA) positive as determined by the central laboratory.
  • Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA.
  • Any of the following laboratory values at screening:
Show all 13Show fewer
  • Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
  • CD4+ T-cells < 200 cells/mm^3 (Cohort 1); CD4+ T-cells < 350 cells/mm^3 (cohort 2).
  • Absolute lymphocyte count < 900 cells/mm^3 (cohort 2).
  • Individuals of childbearing potential (as defined in protocol) who have a positive serum pregnancy test at screening or positive urine and serum pregnancy tests at Day 1 prior to study drug administration.
  • Individuals who plan to continue breastfeeding during the study.
  • Documented historical or screening resistance reports showing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) resistance mutations in reverse transcriptase, including M184V/I (Cohort 2).
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

44 sites in 1 country.

44 sites in 1 country

United States44 sites

  • Emory University Hospital Midtown Infectious Disease Clinic

    Atlanta, Georgia, 30308

  • Atlanta ID Group, PC

    Atlanta, Georgia, 30309

  • Central Texas Clinical Research, LLC

    Austin, Texas, 78705

  • Be Well Medical Center

    Berkley, Michigan, 48072

  • Pacific Oaks Medical Group

    Beverly Hills, California, 90211

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • AccessHealth MA

    Boston, Massachusetts, 02129

  • NC TraCS Institute - CTRC: University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Howard Brown Health Center

    Chicago, Illinois, 60613

  • Northstar Healthcare

    Chicago, Illinois, 60657

  • AIDS Arms Inc

    Dallas, Texas, 75208

  • North Texas Infectious Diseases Consultants, P.A.

    Dallas, Texas, 75246

  • Metro Infectious Disease Consultants

    Decatur, Georgia, 30033

  • Public Health Institute at Denver Health

    Denver, Colorado, 80204

  • Vivent Health

    Denver, Colorado, 80246

  • New York-Presbyterian Queens

    Flushing, New York, 11355

  • CAN Community Health Care, Inc.

    Fort Lauderdale, Florida, 33316

  • Midway Immunology and Research Center

    Ft. Pierce, Florida, 34982

  • ID Care

    Hillsborough, New Jersey, 08844

  • John A. Burns School of Medicine, University of Hawaii Clinics at Kaka'ako

    Honolulu, Hawaii, 96813

  • The Crofoot Research Center, INC

    Houston, Texas, 77098

  • Indiana CTSI Clinical Research Center

    Indianapolis, Indiana, 46202

  • JEM Research Institute

    Lake Worth, Florida, 33462

  • Huntridge Family Clinic

    Las Vegas, Nevada, 89104

  • Ruane Clinical Research Group, Inc

    Los Angeles, California, 90036

  • Mills Clinical Research

    Los Angeles, California, 90069

  • Schiff Center for Liver Diseases/University of Miami

    Miami, Florida, 33136

  • Floridian Clinical Research

    Miami Lakes, Florida, 33016

  • Hennepin Healthcare HCMC

    New Brighton, Minnesota, 55112

  • Hoag Medical Group - Newport Beach

    Newport Beach, California, 92663

  • Orlando Immunology Center

    Orlando, Florida, 32803

  • BIOS Clinical Research

    Palm Springs, California, 92262

  • Penn Medicine: Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Philadelphia FIGHT Community Health Centers

    Philadelphia, Pennsylvania, 19107

  • Optimus Medical Group

    San Francisco, California, 94102

  • AXCES Research Group

    Santa Fe, New Mexico, 87505

  • Chatham County Health Department

    Savannah, Georgia, 31401

  • Peter Shalit, M.D.

    Seattle, Washington, 98104

  • MultiCare Rockwood Main Clinic

    Spokane, Washington, 99202

  • Southampton Healthcare, Inc.

    St Louis, Missouri, 63139

  • Community Health Care

    Tacoma, Washington, 98405

  • Jacobi Medical Center

    The Bronx, New York, 10461

  • Washington Health Institute

    Washington D.C., District of Columbia, 20017

  • The George Washington University Medical Faculty Associates Inc.

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: 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

The primary objective of this study is to evaluate the efficacy of oral weekly islatravir (ISL) in combination with lenacapavir (LEN) in virologically suppressed people with HIV (PWH) at Week 24.

Conditions
HIV-1 Infection
Being tested
ISL, LEN, B/F/TAF, ISL/LEN FDC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ISLDrug

    Capsules administered orally without regard to food

  • LENDrug

    Also called GS-6207

    Tablets administered orally without regard to food

  • B/F/TAFDrug

    Also called Biktarvy®

    Tablets administered orally without regard to food

  • ISL/LEN FDCDrug

    Tablets administered orally without regard to food

Study groups in NCT05052996
Study groupRoleWhat they receive
Cohort 1 (ISL+LEN)ExperimentalParticipants will receive the following for at least 48 weeks: * Day 1 and Day 2: ISL 40 and LEN 600 mg * Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg
Receives: Drug: ISL; Drug: LEN
Cohort 1 (B/F/TAF to ISL+LEN)ExperimentalParticipants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks After 48 weeks, participants will switch from B/F/TAF to ISL+LEN * ISL 40 and LEN 600 mg on Day 1 and Day 2 * ISL 20 mg and LEN 300 mg weekly Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.
Receives: Drug: ISL; Drug: LEN; Drug: B/F/TAF
Cohort 2 (ISL+LEN)ExperimentalParticipants will receive the following for at least 48 weeks * Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) * Day 2: LEN only oral 600 mg (2 x 300 mg) * Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg
Receives: Drug: ISL; Drug: LEN
Cohort 2 (B/F/TAF to ISL+LEN)ExperimentalParticipants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks.
Receives: Drug: ISL; Drug: LEN; Drug: B/F/TAF
Extension Phase Cohort 2 of ISL/LEN Fixed Dose Combination (FDC)ExperimentalAfter 48 Weeks of randomized treatment, all participants will be given an option to participate in an Extension Phase to receive ISL+LEN or ISL/LEN FDC tablet (when available) until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first. Participants receiving ISL+LEN during the randomized phase will continue to take ISL + LEN weekly. Participants receiving B/F/TAF during the randomized phase will switch to ISL+LEN: * Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) * Day 2: LEN only oral 600 mg (2 x 300 mg) * Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study. All participants in the extension phase will be transitioned to weekly ISL/LEN FDC (Dose A) tablet when it becomes available.
Receives: Drug: ISL/LEN FDC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm

    The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.

    Measured: Week 24

Secondary outcomes (19)

  1. Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

    The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off.

    Measured: Week 12

  2. Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

    The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off.

    Measured: Week 48

  3. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off.

    Measured: Week 12

  4. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm

    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.

    Measured: Week 24

  5. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off.

    Measured: Week 48

  6. Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12

    Measured: Baseline and Week 12

  7. Change From Baseline in CD4+ Cell Count at Week 24

    Measured: Baseline and Week 24

  8. Change From Baseline in CD4+ Cell Count at Week 48

    Measured: Baseline and Week 48

  9. Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation

    TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. Percentages were rounded off.

    Measured: Up to 5 years

  10. Cohort 1: Plasma Concentrations for ISL

    Measured: Anytime postdose at Week 4

  11. Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL)

    Cmax was defined as the maximum observed concentration of drug.

    Measured: Anytime post dose on Day 1 and at either Week 12 or Week 18

  12. Cohort 2: PK Parameter: Tmax of ISL

    Tmax was defined as the time (observed time point) of Cmax.

    Measured: Anytime post dose on Day 1 and at either Week 12 or Week 18

  13. Cohort 2: PK Parameter: Ctau of ISL

    Ctau was defined as the observed drug concentration at the end of the dosing interval.

    Measured: Anytime post dose at either Week 12 or Week 18

  14. Cohort 2: PK Parameter: AUCtau of ISL

    AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

    Measured: Anytime post dose at either Week 12 or Week 18

  15. Plasma Concentrations for LEN

    Measured: Anytime postdose at Week 4

  16. Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN

    Cmax was defined as the maximum observed concentration of drug.

    Measured: Anytime post dose on Day 1, Day 2 and at either Week 12 or 18

  17. Cohort 2: PK Parameter: Tmax of LEN

    Tmax is defined as the time (observed time point) of Cmax.

    Measured: Anytime post dose on Day 1, Day 2 and at either Week 12 or Week 18

  18. Cohort 2: PK Parameter: Ctau of LEN

    Ctau was defined as the observed drug concentration at the end of the dosing interval.

    Measured: Anytime post dose at either Week 12 or Week 18

  19. Cohort 2: PK Parameter: AUCtau of LEN

    AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

    Measured: Anytime post dose at either Week 12 or Week 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Sep 2021
  2. Study start5 Oct 2021
  3. Primary completion19 Dec 2023
  4. Study completionMar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
142 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05052996
Sponsor's protocol ID
GS-US-563-6041
Status last verified
Jan 2026
First submitted
13 Sep 2021
Last updated
4 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Colson AE, Crofoot GE, Ruane PJ, Ramgopal MN, Dretler AW, Nahass RG, Sinclair GI, Berhe M, Roberts A, Applin S, Brinson C, Jayaweera D, Workowski KA, Shihadeh F, Liu SY, Klopfer S, Llamoso C, Madera S, Dvory-Sobol H, Rhee MS, Rhee EG, Baeten JM, Eron JJ. Once-Weekly Oral Islatravir Plus Lenacapavir Versus Daily Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Persons With HIV-1 : A Phase 2 Randomized Study. Ann Intern Med. 2026 Feb;179(2):168-176. doi: 10.7326/ANNALS-25-01939. Epub 2025 Dec 23.

    PubMed 41429026

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ISL, LEN and B/F/TAF in people with HIV-1 Infection, run by Gilead Sciences at 44 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05052996, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2026.

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