HIV-1 Infection
Conditions
Brief summary
This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection.
Interventions
DRUGIslatravir
Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.
DRUGPlacebo to Islatravir
Placebo to islatravir is orally administered QD in capsule form for up to 52 weeks
DRUGDoravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks
DRUGPlacebo to Doravirine
Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks
DRUGLamivudine
Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks
DRUGPlacebo to Lamivudine
Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks
Fixed dose combination of 100 mg doravirine + 300 mg lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks.
DRUGPlacebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate
Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks
DRUGDoravirine/Islatravir
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Masking in Part 1, including matching placebo. Masking only to dose in Part 2. No masking in Parts 3 and 4.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has HIV-1 infection * Is naïve to anti-retroviral therapy (ART). * Is clinically stable, with no signs or symptoms of acute infection, at the time of entry into the study * Female is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP); but if WOCBP agrees to follow the contraceptive guidance * All participants, male and female, agree to use barrier methods of contraception when engaged in any sexual activity during treatment and for 6 weeks following treatment.
Exclusion criteria
* Is a user of recreational or illicit drugs or has had a history of drug or alcohol abuse or dependence that may interfere with trial participation * Has significant hypersensitivity or other contraindication to any of the components of the study drugs * Has a history of malignancy ≤5 years prior * Female expects to donate eggs at any time during the study * Is breastfeeding or expecting to conceive * A WOCBP who has a positive urine pregnancy test on Day 1 before the first dose of study treatment * Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 * Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study * Requires any of the following prohibited medications: Carbamazepine, Phenobarbital, Phenytoin, Rifabutin, Rifampin, Herbal remedies, St. John's Wort, Modafinil, Bosentan, Nafcillin, Pentostatin * Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing informed consent to participate in this current trial * Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, protease inhibitor, integrase inhibitor * Has active hepatitis C virus (HCV) coinfection defined as detectable HCV RNA or HBV co-infection defined as hepatitis B surface antigen \[HBsAg\]-positive * Has a current (active) diagnosis of acute hepatitis due to any cause * Has previously been randomized in a study and received islatravir (MK-8591), DOR, Doravirine, Tenofovir, Lamivudine, or 3TC.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24 | Week 24 | Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | Week 48 | Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. |
| Number of Participants Experiencing Adverse Events (AEs) up to Week 144 | Up to 144 weeks | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Number of Participants Discontinuing Study Drug Due to AEs up to Week 144 | Up to 144 weeks | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CD4+ T-cell Count at Week 48 | Baseline and Week 48 | Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication. |
| Change From Baseline in CD4+ T-cell Count at Week 96 | Baseline and Week 96 | Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication. |
| Change From Baseline in CD4+ T-cell Count at Week 144 | Baseline and Week 144 | Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication. |
| Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4) | Baseline and Week 192 | Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Week 144 value. The change from baseline in CD4+ T-cell count at Week 192 (Part 4) are reported. |
| Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | Up to 24 weeks | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment) | Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52. |
| Number of Participants Experiencing AEs From Week 96 Through Study Duration | Week 96 up to Week 192 | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration | Week 96 up to Week 192 | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. |
| Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4) | Week 144 up to Week 192 | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced AEs during Part 4 are reported. |
| Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4) | Week 144 up to Week 192 | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued the study drug due to AEs in Part 4 are reported. |
| Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | Up to 24 weeks | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen | Up to 48 weeks | Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4) | Up to Week 192 | Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. The percentage of participants with HIV-1 RNA \<50 copies in Part 4 are reported. |
| Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24 | Baseline and Week 24 | Blood samples were collected and cluster of differentiation (CD4)+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication. |
Countries
Chile, France, United Kingdom, United States
Participant flow
Recruitment details
Treatment-naïve participants ≥18 years of age with human immunodeficiency virus type 1 (HIV-1) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Islatravir 0.25 mg In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA \<50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192. | 31 |
| Islatravir 0.75 mg In Part 1, participants were treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA \<50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 0.75 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192. | 30 |
| Islatravir 2.25 mg In Part 1, participants were treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. In part 2, after receiving at least 24 weeks of study intervention, participants with HIV-1 RNA \<50 copies/mL and no PDVF discontinued treatment of 3TC and placebo to DOR/3TC/TDF. Part 2 assessed ISL 2.25 mg (blind maintained) + DOR QD. After all participants had received at least 48 weeks of study intervention and the islatravir dose was selected, all participants in the islatravir group were switched to the selected dose 0.75 mg (between week 60 and week 84). Part 3 assessed Islatravir 0.75 mg + DOR QD open label through Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192. | 31 |
| DOR/3TC/TDF In Part 1, participants were treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. In Parts 2 and 3, after a minimum of 24 weeks of treatment, placebo treatments were discontinued and participants received only DOR/3TC/TDF QD open label up to Week 144. In Part 4, beginning with Week 144, participants received the fixed dose combination of doravirine (100 mg)/islatravir (0.75 mg) QD open label and continued treatment until Week 192. | 31 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 3 | 5 | 1 |
| Overall Study | Physician Decision | 4 | 2 | 5 | 4 |
| Overall Study | Screen Failure | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Islatravir 0.25 mg | Islatravir 0.75 mg | Islatravir 2.25 mg | DOR/3TC/TDF | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32.3 Years STANDARD_DEVIATION 13.3 | 30.0 Years STANDARD_DEVIATION 9 | 32.4 Years STANDARD_DEVIATION 11.8 | 29.4 Years STANDARD_DEVIATION 8.9 | 31.0 Years STANDARD_DEVIATION 10.9 |
| CD4+ T-Cell Count | 450.8 cells/mm^3 STANDARD_DEVIATION 170 | 538.5 cells/mm^3 STANDARD_DEVIATION 165.5 | 469.6 cells/mm^3 STANDARD_DEVIATION 203.3 | 508.5 cells/mm^3 STANDARD_DEVIATION 206.8 | 492.1 cells/mm^3 STANDARD_DEVIATION 188.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 19 Participants | 12 Participants | 15 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 11 Participants | 18 Participants | 15 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Participants with <=100,000 copies/mL of HIV-1 RNA | 24 Participants | 23 Participants | 23 Participants | 24 Participants | 94 Participants |
| Participants with >100,000 copies/mL of HIV-1 RNA | 7 Participants | 7 Participants | 8 Participants | 7 Participants | 29 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 6 Participants | 8 Participants | 5 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 24 Participants | 24 Participants | 21 Participants | 24 Participants | 93 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 30 Participants | 27 Participants | 28 Participants | 28 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 | 0 / 31 | 1 / 31 | 0 / 67 | 0 / 22 |
| other Total, other adverse events | 22 / 29 | 26 / 30 | 23 / 31 | 22 / 31 | 21 / 67 | 11 / 22 |
| serious Total, serious adverse events | 2 / 29 | 6 / 30 | 2 / 31 | 4 / 31 | 2 / 67 | 1 / 22 |
Outcome results
Primary
Number of Participants Discontinuing Study Drug Due to AEs up to Week 144
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Time frame: Up to 144 weeks
Population: All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 0.25 mg | Number of Participants Discontinuing Study Drug Due to AEs up to Week 144 | 1 Participants |
| Islatravir 0.75 mg | Number of Participants Discontinuing Study Drug Due to AEs up to Week 144 | 0 Participants |
| Islatravir 2.25 mg | Number of Participants Discontinuing Study Drug Due to AEs up to Week 144 | 2 Participants |
| DOR/3TC/TDF | Number of Participants Discontinuing Study Drug Due to AEs up to Week 144 | 1 Participants |
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-13.4, 14.5]
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-16.4, 8.5]
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-10.8, 18.1]
Primary
Number of Participants Experiencing Adverse Events (AEs) up to Week 144
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Time frame: Up to 144 weeks
Population: All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 0.25 mg | Number of Participants Experiencing Adverse Events (AEs) up to Week 144 | 26 Participants |
| Islatravir 0.75 mg | Number of Participants Experiencing Adverse Events (AEs) up to Week 144 | 27 Participants |
| Islatravir 2.25 mg | Number of Participants Experiencing Adverse Events (AEs) up to Week 144 | 24 Participants |
| DOR/3TC/TDF | Number of Participants Experiencing Adverse Events (AEs) up to Week 144 | 27 Participants |
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-15.7, 20.5]
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-15, 20.8]
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-29.4, 10.1]
Primary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24
Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Time frame: Week 24
Population: All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Islatravir 0.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24 | 93.1 Percentage of participants |
| Islatravir 0.75 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24 | 100.0 Percentage of participants |
| Islatravir 2.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24 | 90.3 Percentage of participants |
| DOR/3TC/TDF | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24 | 90.3 Percentage of participants |
Comparison: Treatment difference in percent response95% CI: [-12.5, 18.3]
Comparison: Treatment difference in percent response95% CI: [-3.8, 23]
Comparison: Treatment difference in percent response95% CI: [-16, 16.3]
Primary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Time frame: Week 48
Population: All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Islatravir 0.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | 89.7 Percentage of participants |
| Islatravir 0.75 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | 90.0 Percentage of participants |
| Islatravir 2.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | 77.4 Percentage of participants |
| DOR/3TC/TDF | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | 83.9 Percentage of participants |
Comparison: Treatment difference in percent response95% CI: [-12.2, 24.4]
Comparison: Treatment difference in percent response95% CI: [-12.2, 24.6]
Comparison: Treatment difference in percent response95% CI: [-27.1, 14.8]
Secondary
Change From Baseline in CD4+ T-cell Count at Week 144
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Time frame: Baseline and Week 144
Population: All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Islatravir 0.25 mg | Change From Baseline in CD4+ T-cell Count at Week 144 | 204.4 cells/mm^3 |
| Islatravir 0.75 mg | Change From Baseline in CD4+ T-cell Count at Week 144 | 209.0 cells/mm^3 |
| Islatravir 2.25 mg | Change From Baseline in CD4+ T-cell Count at Week 144 | 162.9 cells/mm^3 |
| DOR/3TC/TDF | Change From Baseline in CD4+ T-cell Count at Week 144 | 270.0 cells/mm^3 |
Comparison: Treatment difference in T-cell count95% CI: [-195.3, 64]
Comparison: Treatment difference in T-cell count95% CI: [-188.7, 66.8]
Comparison: Treatment difference in T-cell count95% CI: [-231.2, 16.9]
Secondary
Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4)
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Week 144 value. The change from baseline in CD4+ T-cell count at Week 192 (Part 4) are reported.
Time frame: Baseline and Week 192
Population: Per protocol, all randomized participants who entered Part 4 and either continued treatment with DOR/ISL from Part 3 or switched from DOR/3TC/TDF in Part 3 to DOR/ISL in Part 4; and received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data were analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Islatravir 0.25 mg | Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4) | 3.8 cells/mm^3 |
| Islatravir 0.75 mg | Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4) | -3.4 cells/mm^3 |
Secondary
Change From Baseline in CD4+ T-cell Count at Week 48
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Islatravir 0.25 mg | Change From Baseline in CD4+ T-cell Count at Week 48 | 182.0 cells/mm^3 |
| Islatravir 0.75 mg | Change From Baseline in CD4+ T-cell Count at Week 48 | 183.0 cells/mm^3 |
| Islatravir 2.25 mg | Change From Baseline in CD4+ T-cell Count at Week 48 | 100.7 cells/mm^3 |
| DOR/3TC/TDF | Change From Baseline in CD4+ T-cell Count at Week 48 | 181.4 cells/mm^3 |
Comparison: Treatment difference in T-cell count95% CI: [-74.1, 75.3]
Comparison: Treatment difference in T-cell count95% CI: [-70.7, 73.8]
Comparison: Treatment difference in T-cell count95% CI: [-165.6, 4]
Secondary
Change From Baseline in CD4+ T-cell Count at Week 96
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Time frame: Baseline and Week 96
Population: All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Islatravir 0.25 mg | Change From Baseline in CD4+ T-cell Count at Week 96 | 243.4 cells/mm^3 |
| Islatravir 0.75 mg | Change From Baseline in CD4+ T-cell Count at Week 96 | 161.3 cells/mm^3 |
| Islatravir 2.25 mg | Change From Baseline in CD4+ T-cell Count at Week 96 | 136.5 cells/mm^3 |
| DOR/3TC/TDF | Change From Baseline in CD4+ T-cell Count at Week 96 | 268.9 cells/mm^3 |
Comparison: Treatment difference in T-cell count95% CI: [-134.8, 83.8]
Comparison: Treatment difference in T-cell count95% CI: [-212.1, -3.1]
Comparison: Treatment difference in T-cell count95% CI: [-242.9, -21.9]
Secondary
Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24
Blood samples were collected and cluster of differentiation (CD4)+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Time frame: Baseline and Week 24
Population: All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Islatravir 0.25 mg | Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24 | 220.5 cells/mm^3 |
| Islatravir 0.75 mg | Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24 | 192.8 cells/mm^3 |
| Islatravir 2.25 mg | Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24 | 142.9 cells/mm^3 |
| DOR/3TC/TDF | Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24 | 142.1 cells/mm^3 |
Comparison: Treatment difference in T-cell count95% CI: [18.8, 138.1]
Comparison: Treatment difference in T-cell count95% CI: [-31.7, 133.1]
Comparison: Treatment difference in T-cell count95% CI: [-63, 64.7]
Secondary
Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued the study drug due to AEs in Part 4 are reported.
Time frame: Week 144 up to Week 192
Population: Per protocol, all randomized participants who entered Part 4 and either continued treatment with DOR/ISL from Part 3 or switched from DOR/3TC/TDF in Part 3 to DOR/ISL in Part 4; and received at least 1 dose of study treatment, corresponding to the study treatment they actually received were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 0.25 mg | Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4) | 0 Participants |
| Islatravir 0.75 mg | Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4) | 0 Participants |
Secondary
Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Time frame: Week 96 up to Week 192
Population: Per protocol, all randomized participants who received at least 1 dose of open label study treatment in Part 3 or Part 4, corresponding to the study treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 0.25 mg | Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration | 1 Participants |
| Islatravir 0.75 mg | Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration | 0 Participants |
| Islatravir 2.25 mg | Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration | 0 Participants |
| DOR/3TC/TDF | Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration | 0 Participants |
| DOR/ISL Continued | Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration | 0 Participants |
| DOR/ISL Switch | Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration | 0 Participants |
Secondary
Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Time frame: Up to 24 weeks
Population: All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 0.25 mg | Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 0 Participants |
| Islatravir 0.75 mg | Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 0 Participants |
| Islatravir 2.25 mg | Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 2 Participants |
| DOR/3TC/TDF | Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 1 Participants |
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-17.9, 8.5]
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-17.9, 8.2]
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-11.5, 20.6]
Secondary
Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced AEs during Part 4 are reported.
Time frame: Week 144 up to Week 192
Population: Per protocol, all randomized participants who entered Part 4 and either continued treatment with DOR/ISL from Part 3 or switched from DOR/3TC/TDF in Part 3 to DOR/ISL in Part 4; and received at least 1 dose of study treatment, corresponding to the study treatment they actually received were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 0.25 mg | Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4) | 36 Participants |
| Islatravir 0.75 mg | Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4) | 14 Participants |
Secondary
Number of Participants Experiencing AEs From Week 96 Through Study Duration
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Time frame: Week 96 up to Week 192
Population: Per protocol, all randomized participants who received at least 1 dose of open label study treatment in Part 3 or Part 4, corresponding to the study treatment they actually received were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 0.25 mg | Number of Participants Experiencing AEs From Week 96 Through Study Duration | 12 Participants |
| Islatravir 0.75 mg | Number of Participants Experiencing AEs From Week 96 Through Study Duration | 19 Participants |
| Islatravir 2.25 mg | Number of Participants Experiencing AEs From Week 96 Through Study Duration | 11 Participants |
| DOR/3TC/TDF | Number of Participants Experiencing AEs From Week 96 Through Study Duration | 12 Participants |
| DOR/ISL Continued | Number of Participants Experiencing AEs From Week 96 Through Study Duration | 36 Participants |
| DOR/ISL Switch | Number of Participants Experiencing AEs From Week 96 Through Study Duration | 14 Participants |
Secondary
Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Time frame: Up to 24 weeks
Population: All randomized participants who received at least 1 dose of study treatment, corresponding to the study treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Islatravir 0.25 mg | Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 18 Participants |
| Islatravir 0.75 mg | Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 20 Participants |
| Islatravir 2.25 mg | Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 14 Participants |
| DOR/3TC/TDF | Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 16 Participants |
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-20.3, 29.6]
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-15.4, 33.5]
Comparison: Difference in % Islatravir vs DOR/3TC/TDF95% CI: [-30.6, 20.7]
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Time frame: Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment)
Population: All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Islatravir 0.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 86.2 Percentage of participants |
| Islatravir 0.75 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 90.0 Percentage of participants |
| Islatravir 2.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 88.9 Percentage of participants |
| DOR/3TC/TDF | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 96.4 Percentage of participants |
Comparison: Treatment difference in percent response95% CI: [-26.1, 6.6]
Comparison: Treatment difference in percent response95% CI: [-21.5, 9.1]
Comparison: Treatment difference in percent response95% CI: [-23.9, 8.8]
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Time frame: Up to 48 weeks
Population: All randomized participants who received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Islatravir 0.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 62.1 Percentage of participants |
| Islatravir 0.75 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 56.7 Percentage of participants |
| Islatravir 2.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 59.3 Percentage of participants |
| DOR/3TC/TDF | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen | 60.7 Percentage of participants |
Comparison: Treatment difference in percent response95% CI: [-23.4, 27.7]
Comparison: Treatment difference in percent response95% CI: [-29.6, 22.1]
Comparison: Treatment difference in percent response95% CI: [-27.7, 25.2]
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4)
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. The percentage of participants with HIV-1 RNA \<50 copies in Part 4 are reported.
Time frame: Up to Week 192
Population: Per protocol, all randomized participants who entered Part 4 and either continued treatment with DOR/ISL from Part 3 or switched from DOR/3TC/TDF in Part 3 to DOR/ISL in Part 4; and received at least 1 dose of study treatment and have baseline data for those analyses that require baseline data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Islatravir 0.25 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4) | 85.1 Percentage of participants |
| Islatravir 0.75 mg | Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4) | 95.5 Percentage of participants |