Lenacapavir (LEN)

Investigational Use With Islatravir

This document is in response to your request for information regarding clinical study data on lenacapavir (LEN) and its use in combination with the investigational agent islatravir (ISL) developed by Merck & Co., Inc., Kenilworth, NJ, USA.

Gilead Sciences, Inc. is providing this document to you, a US Healthcare Professional, in response to your unsolicited request for medical information. The information in this document is about an investigational regimen, and the safety and efficacy of these treatments when used in combination has not been established. This document is not intended to offer an opinion regarding the safety and efficacy of this investigational regimen. The use of ISL + LEN for the treatment of HIV-1 is investigational and is not approved by the US FDA or any other regulatory authority for use in patients.

Summary

Phase 3 Clinical Studies on the Use of LEN and ISL

ISLEND-1 is an ongoing phase 3, randomized, double-blind, active-controlled study evaluating a switch to oral once-weekly ISL/LEN STR in PWH who were VS on BIC/FTC/TAF.1

• At Week 48, high rates of virologic suppression were maintained, with 0% in the ISL/LEN group and 0.3% in the BIC/FTC/TAF group with HIV-1 RNA ≥50 c/mL (treatment difference, 0.3%; 95.002% CI: -1.4 to 0.8%).
• In the ISL/LEN group, no participants developed resistance to either component, and rates of virologic suppression were similar between those with and without M184V/I at baseline.
• Most AEs and TRAEs were Grade 1 or 2 in severity. Discontinuations due to AEs occurred in 2% and 1.7% of participants in the ISL/LEN and BIC/FTC/TAF groups, respectively.

ISLEND-2 is a phase 3, randomized, open-label, active-controlled study evaluating a switch to oral once-weekly ISL/LEN STR in PWH who were VS on an SOC ARV regimen.2

• At Week 48, high rates of virologic suppression were noted, with 0.3% in the ISL/LEN group and 1.3% in the SOC group with HIV-1 RNA ≥50 c/mL (treatment difference, ‑1%; 95.002% CI: -3 to 1.1%). 
• In the ISL/LEN group, no participants developed resistance to either component.
• No Grade ≥3 TRAEs occurred in either group; 1 treatment-related SAE occurred in the ISL/LEN group, and none occurred in the SOC group. Discontinuations due to AEs occurred in 7% and 9% of participants in the ISL/LEN and SOC groups, respectively.

Phase 2 Clinical Studies on the Use of LEN and ISL

Study GS-US-563-6041, a phase 2, open-label, active-controlled clinical trial, evaluated switching to oral once-weekly doses of ISL 2 mg + LEN 300 mg or remaining on BIC/FTC/TAF daily in VS PWH. The study was not powered for analysis.3

• With ISL + LEN and BIC/FTC/TAF treatment, virologic suppression was maintained at Week 24 (HIV‑1 RNA ≥50 c/mL: 1.9% vs 0%, respectively; treatment difference of 1.9%; 95% CI: -5.2 to 10.5%) and Week 48 (0% vs 0%).3
• All enrolled PWH had the option to continue into the OLE phase after 48 weeks. The early switch group consisted of participants initially randomized to oral ISL + LEN, and the late switch group comprised those initially randomized to BIC/FTC/TAF before switching to ISL + LEN.4,5
  • All participants in the OLE phase had HIV RNA ≤50 c/mL at Week 96, including a participant with preexisting M184V.6
  • No treatment-emergent resistance to ISL or LEN was detected in either group.4,5
  • No treatment-related Grade ≥3 AEs, SAEs, or AEs that led to study drug discontinuation were reported.4-6

Phase 3 Clinical Studies on the Use of LEN and ISL

ISLEND-1 Study

Study design and demographics1,7

ISLEND-1 (NCT06630286) is an ongoing, phase 3, randomized, double-blind, active‑controlled, noninferiority study comparing efficacy and safety outcomes between VS PWH treated with BIC/FTC/TAF who switched to once-weekly oral ISL/LEN or remained on once‑daily oral BIC/FTC/TAF (Figure 1). The primary endpoint is the proportion of participants with HIV-1 RNA ≥50 c/mL at Week 48 per FDA Snapshot algorithm (noninferiority margin, 4%).

Figure 1. ISLEND-1: Study Design1,7,8

aNot positive for HBsAg or not positive for HBcAb and negative for HBsAb.

bLoading dose: 2 tablets of ISL/LEN (each containing 0.5 mg ISL and 300 mg LEN) on Days 1 and 2. Matching ISL/LEN placebo loading dose strategy was used in the BIC/FTC/TAF group. Maintenance dose: 1 tablet (containing 2 mg ISL and 300 LEN) once weekly starting on Day 8; matching ISL/LEN placebo was used in the BIC/FTC/TAF group. Both treatments were administered with or without food.

cOpen-label ISL/LEN to continue until it becomes commercially available or the study is discontinued, whichever comes first.

dTreatment‑emergent resistance testing performed for participants with confirmed VF (HIV-1 RNA >50 c/mL at any timepoint post-baseline or at the last visit on-treatment); genotypic and phenotypic testing was performed for those with HIV-1 RNA ≥200 c/mL.

Baseline demographics and disease characteristics are presented below (Table 1).

Table 1. ISLEND-1: Baseline Demographics and Disease Characteristics1

aThese data were reported by the participants. bData were not available for 1 participant.

Week 48 results

Efficacy1

The primary analysis included 304 participants in the ISL/LEN group and 303 in the BIC/FTC/TAF group; 283 and 279 participants, respectively, continued their assigned treatment after Week 48.

At Week 48, ISL/LEN demonstrated noninferior efficacy compared with staying on BIC/FTC/TAF (HIV-1 RNA ≥50 c/mL [primary endpoint], 0 vs 0.3%, respectively; Figure 2). This resulted in a treatment difference of -0.3% (95.002% CI: -1.4 to 0.8%; Mantel-Haenszel analysis adjusted for geographic region [US vs outside US]). These results were consistent with a per-protocol analysis and sensitivity analyses.

Regarding the secondary endpoint of HIV-1 RNA <50 c/mL, ISL/LEN was noninferior vs BIC/FTC/TAF per FDA Snapshot: 93.4% vs 92.4%, respectively (treatment difference, 1%; 95.002% CI: -3.2 to 5%).

Figure 2. ISLEND-1: Virologic Outcomes at Week 481

In the ISL/LEN group, no participants developed resistance to either component, and rates of virologic suppression (HIV-1 RNA <50 c/mL) were similar between those with and without the M184V/I mutation at baseline: 92.3% (n/N=12/13) vs 93.7% (n/N=254/271), respectively.

Safety

Most AEs and TRAEs were Grade 1 or 2 in severity (90.8% of those with any AE and 98.8% of those with any TRAE). No deaths occurred in either group. Safety outcomes are summarized in Table 2.1,9

Due to the concern regarding potential unblinding, AEs that occurred infrequently were not attributed to a treatment group. One Grade 3 treatment-related SAE of maculopapular rash occurred in a study participant (treatment group not indicated) with a history of asthma and drug allergies. One participant (treatment group not indicated) discontinued treatment after incident HBV was reported on Day 183; this participant was unvaccinated and was positive for HBsAg at Week 24 and for HBcAb at a subsequent visit. Previously elevated liver enzyme levels were noted to be normalized at the participant’s Day 60 follow-up visit.1

Table 2. ISLEND-1: Safety Outcomes Through Week 481,9

aDue to the potential for unblinding with AEs that occurred at a low frequency, no AEs were attributed to the treatment groups.

bNo Grade 3 AEs were reported in >1 participant; those that occurred in 1 participant (<1%) included abdominal pain, asthma, and syncope.

cGrade 3 treatment-related SAE of maculopapular rash.

dThe only AE that occurred in >1 participant and resulted in treatment discontinuation was arthralgia (n=2; 0.7% overall; considered treatment-related by the investigator); their treatment group was not reported.

The mean change from baseline to Week 48 in CD4 count was -10 cells/mcL in the ISL/LEN group and ‑18 cells/mcL in the BIC/FTC/TAF group (LSM difference [95% CI], 12 [‑16 to 39] cells/mcL). No participants in either group discontinued treatment due to a decrease in CD4 count.1

The mean ± SD change from baseline to Week 48 in lymphocyte count was 0.08±0.416 ×103 cells/mcL in the ISL/LEN group and 0.08±0.493 ×103 cells/mcL in the BIC/FTC/TAF group. No participants discontinued study treatment due to decreases in lymphocyte counts.1

The mean ± SD change and percent change in body weight from baseline to Week 48 was numerically similar between treatment groups overall: ISL/LEN, -0.8±5.28 kg; BIC/FTC/TAF, +0.1±5.65 kg. These results were similar when stratified by sex.1,10

Mean ± SD adherence rates, as assessed by pill counts, were 98.9±6.71% and 95.8±9.74% in the ISL/LEN and BIC/FTC/TAF groups, respectively. Adherence rates ≥95% were achieved by numerically more participants in the ISL/LEN group than in the BIC/FTC/TAF group: 96% vs 80.4%, respectively.1,9

ISLEND-2 Study

Study design and demographics2

ISLEND-2 (NCT06630299) is an ongoing, phase 3, randomized, open-label, active‑controlled, noninferiority study evaluating efficacy and safety outcomes of VS PWH receiving an SOC ARV regimen who switched to once-weekly oral ISL/LEN or remained on a daily SOC ARV regimen (Figure 3). The primary endpoint is the proportion of participants with HIV-1 RNA ≥50 c/mL at Week 48 per FDA Snapshot algorithm (noninferiority margin, 4%).

Figure 3. ISLEND-2: Study Design2,11

aSOC was administered once daily as fixed-dose combinations or STRs, except for raltegravir (dosed once or twice daily).

bHBsAg positive or HBcAb/HBsAb negative.

cLoading dose: 2 tablets of ISL/LEN (each containing 0.5 mg ISL and 300 mg LEN) on Days 1 and 2. Maintenance dose: 1 tablet (containing 2 mg ISL and 300 LEN) once weekly starting on Day 8. ISL/LEN was administered with or without food.

dOpen-label ISL/LEN to continue until it becomes commercially available or the study is discontinued, whichever comes first.

Baseline demographics and disease characteristics are presented in Table 3.

Table 3. ISLEND-2: Baseline Demographics and Disease Characteristics2

Abbreviations: 3TC=lamivudine; DTG=dolutegravir.

aLocal regulations prohibited data collection of race (ISL/LEN, n=12 [4%]; SOC, n=11 [4%]) and ethnicity (ISL/LEN, n=16 [5%]; SOC, n=12 [4%]).

bIncluded American Indian or Alaska Native or other.

Week 48 results

Efficacy2

At Week 48, ISL/LEN demonstrated noninferior efficacy (HIV-1 RNA ≥50 c/mL; primary endpoint) compared with staying on SOC (0.3% vs 1.3%, respectively; Figure 4). This resulted in a treatment difference of -1% (95.002% CI: -3 to 1.1%; Mantel‑Haenszel analysis adjusted for geographic region [US vs outside US] and ARV class [INSTI, NNRTI, and PI]). ISL/LEN was deemed non-inferior to SOC but not superior to SOC, with the upper bound of the 95.002% CI <4% and >0%.

For the secondary endpoint of HIV-1 RNA <50 c/mL, similar rates of suppression were noted: ISL/LEN, 95.2%; SOC, 95.5% (Figure 4). In the ISL/LEN group, no participants developed resistance to either component; the participant with HIV-1 RNA ≥50 c/mL had low-level viremia (104 c/mL at Week 48), did not meet the criteria for resistance testing, and was resuppressed on ISL/LEN at Week 60. Three of the 4 participants in the SOC group with HIV‑1 RNA ≥50 c/mL did not meet criteria for resistance testing and were later resuppressed. The fourth participant had HIV-1 RNA of 621 c/mL at Week 48 and was resuppressed at Week 60, and their resistance testing was conducted twice (both resulted in assay failure).

Figure 4. ISLEND-2: Virologic Outcomes at Week 482

Safety

The median (IQR) exposure to ISL/LEN was 60 (56.1–66.4) weeks and 59.3 (55.6–‍65.2) weeks for SOC. Treatment with ISL/LEN was well tolerated, and no Grade ≥3 TRAEs occurred in either group. All TRAEs were Grade 1 or 2 in severity One treatment-related SAE of seizure occurred in a participant who missed 2 doses of antiseizure medication in the ISL/LEN group (no interruptions of ISL/LEN doses); none occurred in the SOC group.2

Table 4. ISLEND-2: Safety Outcomes Through Week 482,11

aOnly two Grade ≥3 treatment-emergent AEs occurred in >1 participant: acute kidney injury (ISL/LEN, n=2 [0.6%]); SOC, n=3 [1%]) and road traffic accident (ISL/LEN, n=2 [0.6%]; SOC, n=0).

bGrade 2 seizure in a participant who missed 2 doses of antiseizure medication, n=1.

cTreatment-related hyperbilirubinemia in a participant with a history of hyperbilirubinemia, n=1; acute HBV unrelated to treatment in a participant with no priori immunity to HBV, n=1.

dCentral nervous system lymphoma unrelated to treatment, n=1.

eRoad traffic accident, n=1; unrelated to study drug.

fPneumonia, which was complicated by cardiogenic shock/cardiac arrest, n=1; central nervous system lymphoma, n=1. None were deemed to be related to study drug.

Among the participants who had a Grade ≥3 increase in direct bilirubin, most increases were not clinically significant, with median (IQR) changes from baseline of +0.1 (-0.2 to 0.05) mg/dL in the ISL/LEN group and ‑0.01 (‑0.04 to 0.02) mg/dL in the SOC group. Among those with clinically significant increases, most participants had underlying health conditions or concomitant medications that were identified as causes of the increases. Three participants in the ISL/LEN group with elevated direct bilirubin levels also had elevations in other liver parameters (n=1 each: acute syphilis treated with penicillin, acute HBV infection, and gastroenteritis), and all had normalized or improved values at the next study visits.2

The mean percent (95% CI) change from baseline to Week 48 in CD4 count was -0.2% (‑4.2% to 3.9%) in the ISL/LEN group and +2.4% (-0.8% to 5.6%) in the SOC group (LSM difference [95% CI], ‑2% [‑6.8% to 2.8%]). No participants in either group discontinued treatment due to a decrease in CD4 count.2

In a post hoc analysis using the mean CD4 count at baseline and Day 1, the mean ± SD change from baseline to Week 48 was -43±165 cells/mcL in the ISL/LEN group and
‑17±160.6 cells/mcL in the SOC group (treatment difference [95% CI]: -23 [-47 to 2] cells/mcL).2

In an analysis of changes in CD4 count categories (<200, 200 to <350, 350 to <500, and ≥500 cells/mcL) from baseline and Week 48 in participants with available data (ISL/LEN, n=301; SOC, n=302), 21 participants (7%) moved to a lower category and 26 (9%) moved to a higher category in the ISL/LEN group, whereas 20 participants (7%) moved to a lower category and 24 (8%) moved to a higher category in the SOC group.2

Mean ± SD changes from baseline through Week 48 in lymphocyte counts were generally stable in each group: ISL/LEN, -0.02±0.442× 103 cells/mcL; SOC, 0.1±0.447 × 103 cells/mcL. No participants discontinued study treatment due to decreases in lymphocyte counts.2

Through Week 48, mean ± SD changes in body weight in each group were minimal: ISL/LEN, +0.1±4.74 kg; SOC, -0.3±4.12 kg.2

Two pregnancies occurred during the study. In the ISL/LEN group, 1 participant who had preexisting Type 2 diabetes mellitus became pregnant and was admitted to the hospital due to poor glycemic control; they delivered an infant with reassuring Apgar scores at gestation Week 33. A participant in the SOC group became pregnant, stayed in the study, and later had a spontaneous abortion (considered a Grade ≥3 AE and an SAE; not considered to be treatment-related).2,11

Adherence2,11

Adherence rates were calculated as follows: (total number of tablets administered/tablets expected to be administered on treatment) × 100. For assessments of adherence level, the denominator for calculations was the number of participants who were on treatment, returned ≥1 study bottle, and had calculable adherence data. The median adherence rate was 100% in the ISL/LEN group, and most participants (98%; n/N=307/312) took ≥90% of the ISL/LEN doses. Of the 5 participants with an adherence rate <90% (3 had a rate <80%), 4 had an HIV-1 RNA <50 c/mL at Week 48, and 1 discontinued participation in the study while VS due to a protocol violation.

Phase 2 Clinical Studies on the Use of LEN and ISL

Study GS-US-563-6041

Study design and demographics3

Study GS-US-563-6041 (NCT05052996) is an ongoing, phase 2, open-label, active‑controlled clinical trial comparing efficacy and safety in VS PWH treated with BIC/FTC/TAF who switched to weekly doses of oral ISL 2 mg + LEN 300 mg or remained on once-daily BIC/FTC/TAF (Figure 5). The primary endpoint is the proportion of participants with HIV-1 RNA ≥50 c/mL at Week 24 per the FDA Snapshot algorithm. The study was not powered for analysis.

Figure 5. GS-US-563-6041: Study Design3,12

aDose: 2 mg (2 × 1 mg capsule) ISL on Day 1 and every week thereafter starting on Day 8.

bLoading dose: 600 mg (2 × 300 mg tablets) LEN on Day 1 and Day 2. Maintenance dose: 300 mg (1 × 300 mg tablet) on Day 8 and every week thereafter.

Baseline demographics and disease characteristics are presented below (Table 5).

Table 5. GS-US-563-6041: Baseline Demographic and Disease Characteristics3

Week 24 and 48 results

Efficacy3

At Week 24, 1 participant (1.9%) in the ISL + LEN group and none in the BIC/FTC/TAF group had HIV‑1 RNA ≥50 c/mL (primary endpoint); this resulted in a treatment difference of 1.9% (95% CI: -5.2 to 10.5%). The ISL + LEN participant had HIV-1 RNA levels of 251 c/mL on Day 1 and <200 c/mL at Week 24 and was suppressed after Week 36 and maintained virologic suppression through Week 48 on ISL + LEN. This participant did not develop resistance to either component by genotypic or phenotypic analysis. In both groups, 94.2% of participants achieved HIV-1 RNA <50 c/mL at Week 24; data were missing for 2 participants (3.8%) in the ISL + LEN group and 3 (5.8%) in the BIC/FTC/TAF group.

At Week 48, 94.2% of participants were VS in the ISL + LEN group and 92.3% were in the BIC/FTC/FTC group (treatment difference: 1.9%; 95% CI: -9.3 to 13.6%). No participants in the either group had HIV-1 RNA ≥50 c/mL; data were missing for 3 participants (5.8%) in the ISL + LEN group and 4 (7.7%) in the BIC/FTC/TAF group. None of the participants with missing data at Week 24 or 48 had virologic rebound (HIV-1 RNA ≥50 c/mL) at their last visit with available data.

At Week 48, 3 participants discontinued ISL + LEN (AEs unrelated to study drug, n=2; other reasons, n=1), and 4 discontinued BIC/FTC/TAF (reasons not related to study drug, n=3; missing data but remained on study drug, n=1). All participants had HIV-1 RNA <50 c/mL at study discontinuation.

Safety and adherence3

At Week 48, no Grade ≥3 AEs, SAEs, or AEs leading to study drug discontinuation were related to study drug. All TRAEs were Grade 1 or 2 in severity (ISL + LEN, 19.2%; BIC/FTC/TAF, 5.8%); the only TRAEs that occurred in ≥2 participants in the ISL + LEN group were dry mouth and nausea (each, 3.8%). No Grade 3 and 4 laboratory abnormalities were clinically significant, except for alanine aminotransferase elevation in a participant in the ISL + LEN group with acute HBV infection.

There were no significant differences between groups in mean change from baseline in CD4 cell or lymphocyte counts at Week 48. No participants discontinued due to CD4 cell or lymphocyte count decreases.

The median (IQR) adherence rate was 100% (98.8–100%) in the ISL + LEN group and 98.8% (97.1–‍100%) in the BIC/FTC/TAF group. A higher proportion of participants in the ISL + LEN group than in the BIC/FTC/TAF group had an adherence rate of ≥95%: 98% vs 86.3%, respectively.

Week 96 results

Efficacy

All enrolled participants had the option to continue into a 48-week extension phase to receive ISL + LEN. The early switch group consisted of the 52 participants initially randomized to receive ISL + LEN and continued on it in the OLE, and the late switch group consisted of the 45 participants who were initially randomly assigned to receive BIC/FTC/TAF and switched to ISL + LEN in the OLE.4,5 Baseline characteristics were similar between the two OLE groups; overall, the median age was 40 years, 18.6% were assigned female at birth, and 50.5% were White.5

At Week 96, all participants in both treatment groups with virologic data available had HIV-1 RNA ≤50 c/mL (early switch group, 88.5% [n/N=46/52]; late switch group, 97.8% [n/N=44/45]). Data were unavailable for 11.5% of participants (n/N=6/52) in the early switch and 2.2% (n/N=1/45) in the late switch group.4,5

Safety and adherence4,5

No Grade ≥3 TRAEs, SAEs, or AEs related to ISL + LEN that led to study drug discontinuation were reported (Table 6).

Table 6. GS-US-563-6041: Safety Outcomes With ISL + LEN Through Week 964,5

aNeurologic anesthesia complication (n=1), renal colic/colon perforation in the same participant (n=1); pneumonia (n=1).

bAcute HBV infection (n=1) and renal colic/colon perforation (n=1) in the same participant. These were not considered TRAEs.

There were no clinically significant changes in CD4 or lymphocyte counts from baseline through Week 96 in both groups. Body weight and body mass index remained stable from baseline through Week 96 in both groups.

Mean adherence to weekly oral ISL + LEN, as calculated by pill count, remained high in the early switch (99.3%) and late switch (98.6%) treatment groups. No VF was observed, and no emergent resistance to ISL or LEN was detected.

Terms of Collaboration13

Under the terms of the agreement, Gilead and Merck will co-develop and co-commercialize long-acting products to treat PWH that combine Gilead’s LEN and Merck’s proprietary investigational nucleoside reverse transcriptase translocation inhibitor, ISL. The collaboration will initially focus on long-acting oral formulations and long-acting injectable formulations of these combination products, with other formulations potentially added to the collaboration as mutually agreed.

References

1. Rockstroh JK, Ramgopal MN, Curran Fabregas A, et al. Phase 3 Trial of Weekly Oral Islatravir-Lenacapavir for HIV-1 Treatment. N Engl J Med. 2026:1-11.

2. Colson AE, Kumar PN, Ruane PJ, et al. Switch to once-weekly, single-tablet islatravir-lenacapavir from daily standard of care for HIV-1 (ISLEND-2): a multicentre, randomised, open-label, active-controlled, phase 3 non-inferiority trial. Lancet. 2026;408(10557):821-832.

3. Colson AE, Crofoot GE, Ruane PJ, et al. 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;179(2):168-176.

4. Colson AE, Crofoot GE, Ruane PJ, et al. Oral Weekly Islatravir Plus Lenacapavir in Virologically Suppressed People with HIV-1: 96 Week Outcomes from a Phase 2 Study. [Presentation #PS15.5.LB]. Paper presented at: The 20th European AIDS Conference; October 15-18, 2025; Paris, France.

5. Colson AE, Crofoot GE, Ruane PJ, et al. Once-Weekly Islatravir Plus Lenacapavir Mantains HIV-1 Suppression Through 96 Weeks: Phase 2 Study [Poster #516]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2026; Denver, CO.

6. Beckerman E, Chang S, Diamond TL, et al. Resistance Analysis of Weekly Islatravir Plus Lenacapavir in People with HIV at 96 Weeks. [Poster #586]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2026; Denver, CO.

7. National Institutes of Health (NIH). Study to Compare an Oral Weekly Islatravir/ Lenacapavir Regimen With Bictegravir/ Emtricitabine/ Tenofovir Alafenamide in Virologically Suppressed People With HIV-1 (ISLEND-1). Available at: https://clinicaltrials.gov/study/NCT06630286. Accessed: 25 October 2024. Last Updated: 08 October. 2024.

8. Rockstroh JK, Ramgopal MN, Curran Fabregas A, et al. A Phase 3, Randomized, Double-blind, Active-controlled Study to Evaluate a Switch to an Oral Weekly Islatravir/Lenacapavir Regimen in People With HIV-1 Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir (B/F/TAF). Protocol.  26 May 2026.

9. Rockstroh JK, Ramgopal MN, Curran Fabregas A, et al. Phase 3 Trial of Weekly Oral Islatravir-Lenacapavir for HIV-1 Treatment. [Supplementary Appendix]. 2026:1-96.

10. Rockstroh JK, Ramgopal MN, Curran Fabregas A, et al. Once-Weekly Oral Islatravir/Lenacapavir (ISL/LEN) Versus Daily Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in Virologically Suppressed Adults With HIV-1: Week 48 Results of the ISLEND-1 Phase 3 Trial [Presentation OAB1406LB]. Paper presented at: 26th International AIDS Conference; July 26-31, 2026; Rio de Janeiro, Brazil.

11. Colson AE, Kumar PN, Ruane PJ, et al. Switch to once-weekly, single-tablet islatravir-lenacapavir from daily standard of care for HIV-1 (ISLEND-2): a multicentre, randomised, open-label, active-controlled, phase 3 non-inferiority trial [Supplementary appendix]. Lancet. 2026.

12. Colson AE, Crofoot GE, Ruane PJ, et al. Efficacy and Safety of Weekly Islatravir Plus Lenacapavir in PWH at 24 Weeks: A Phase 2 Study.[Presentation Oral-14]. Paper presented at: 31st Conference on Retroviruses and Opportunistic Infections (CROI),; March 3-6, 2024; Denver, Colorado.

13. Gilead and Merck announce agreement to jointly develop and commercialize long-acting, investigational treatment combinations of Lenacapavir and Islatravir in HIV [Press Release]. 15 March [press release]. 2021.

Abbreviations

AE=adverse event
ARV=antiretroviral
BIC=bictegravir
c/mL=copies per mL
CD4=cluster of differentiation 4
FTC=emtricitabine
HBcAb=hepatitis B core antibody
HBsAb=hepatitis B surface antibody
HBsAg=hepatitis B surface antigen
INSTI=integrase strand transfer inhibitor
ISL=islatravir
LEN=lenacapavir
LSM=least-squares mean
NNRTI=non-nucleos(t)ide reverse transcriptase inhibitor
NRTI=nucleos(t)ide reverse transcriptase inhibitor
OLE=open-label extension
PI=protease inhibitor
PK=pharmacokinetic(s)

PRO=participant‑reported outcome
PWH=people with HIV-1
SAE=serious adverse event
SOC=standard of care
STR=single-tablet regimen
TAF=tenofovir alafenamide
TRAE=treatment-related adverse event
VF=virologic failure
VS=virologically suppressed

Follow Up

For any additional questions, please contact Gilead Medical Information at:

☎1‐866‐MEDI‐GSI (1‐866‐633‐4474) or   www.askgileadmedical.com

Adverse Event Reporting

Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 https://www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

Data Privacy

The Medical Information service at Gilead Sciences may collect, store, and use your personal information to provide a response to your medical request. We may share your information with other Gilead Sciences colleagues to ensure that your request is addressed appropriately. If you report an adverse event or concern about the quality of a Gilead or Kite product, we will need to use the information you have given us in order to meet our regulatory requirements in relation to the safety of our medicines.

It may be necessary for us to share your information with Gilead’s affiliates, business partners, service providers, and regulatory authorities located in countries besides your own. Gilead Sciences has implemented measures to protect the personal information you provide. Please see the Gilead Privacy Statement (www.gilead.com/privacy-statements) for more information about how Gilead handles your personal information and your rights. If you have any further questions about the use of your personal information, please contact gilead.privacy@gilead.com.

GILEAD and the GILEAD logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
© 2026 Gilead Sciences, Inc.