Central Nervous System, HIV-1
Conditions
Brief summary
This study aims to evaluate a switch from fixed dose combination (FDC) treatment with ATRIPLA\^TM for 12 weeks prior to screening to FDC treatment with Doravirine, Tenofovir, Lamivudine (MK-1439A) in virologically-suppressed, human immunodeficiency virus type 1 (HIV-1)-infected participants. The primary hypothesis is that switching from ATRIPLA\^TM to Doravirine, Tenofovir, Lamivudine results in a lower proportion of participants with at least one CNS toxicity of at least Grade 2 intensity at Week 12 than continuation of ATRIPLA\^TM treatment.
Interventions
DRUGDoravirine, Tenofovir, Lamivudine - Blinded
A single tablet FDC containing doravirine 100 mg, lamivudine (3TC) 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg administered orally, once daily for 12 weeks during the Blinded period
DRUGDoravirine, Tenofovir, Lamivudine - Open-Label
A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for either 12 or 24 weeks during the Open-Label Period; also an additional 96 weeks during the Open-Label extension period 1; a maximum total duration of treatment of 228 weeks during the Open-Label extension period 2; and a maximum total duration of treatment of 324 weeks during the Open-Label extension period 3.
DRUGATRIPLA^TM
A single tablet FDC containing efavirenz (EFV) 600 mg, emtricitabine (FTC) 200 mg, and TDF 300 mg administered orally, once daily for 12 weeks during the Blinded period
DRUGPlacebo to ATRIPLA™
A single placebo to ATRIPLA™ tablet administered orally, once daily for 12 weeks during the Blinded period
DRUGPlacebo to Doravirine, Tenofovir, Lamivudine
A single placebo to doravirine, tenofovir, lamivudine tablet administered orally, once daily for 12 weeks during the Blinded period
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* is taking ATRIPLA™, generic versions of ATRIPLA™, or the components of ATRIPLA™ (EFV,TDF plus emtricitabine), * has documentation of HIV-1 ribonucleic acid (RNA) \< 50 copies/mL during the 12 weeks prior to screening while on ATRIPLA™. * has plasma HIV-1 RNA levels below the limits of quantification (BLoQ) at the screening visit. * if genotyped prior to starting initial antiretroviral regimen, must have no known resistance to any of the study agents * has at least one EFV-associated CNS toxicities of Grade 2 or worse intensity both at the time of screening and at Study Day 1 * is highly unlikely to become pregnant or to impregnate a partner * To be eligible for study extension 1, participants from Immediate Switch Group (ISG) must have completed Study Week 24, and benefited from study participation; participants from Deferred Switch Group (DSG) must have completed Study Week 36, and benefited from study participation as determined by the investigator * To be eligible for study extension 2, participants from ISG must have completed Study Week 120, and benefited from study participation; participants from DSG must have completed Study Week 132, and benefited from study participation as determined by the investigator
Exclusion criteria
* is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence. * has ongoing Grade 4 CNS toxicity during screening period that requires a prompt change in ART * has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 including, but not limited to, adefovir, emtricitabine, entecavir, lamivudine or tenofovir. * has documented or known resistance to study drugs including doravirine, lamivudine, and/or tenofovir * has participated in, or anticipates participating in a study with an investigational compound/device within 30 days prior to signing informed consent * has used systemic immunosuppressive therapy or immune modulators or anticipates using them within 30 days prior to this study * requires or anticipates requiring any of the prohibited medications * has significant hypersensitivity or other contraindication to any of the components of the study drugs * has a current (active) diagnosis of acute hepatitis due to any cause. * has evidence of decompensated liver disease manifested by the presence of or a history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver diseases, or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score \> 9. * is pregnant, breastfeeding, or expecting to conceive. * female is expecting to donate eggs (at any time during the study) or male is expecting to donate sperm (at any time during the study).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One Central Nervous System (CNS) Toxicity of at Least Grade 2 Intensity at Week 12 | Week 12 | A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Drug-related AEs for the Combined Treatment Groups 24 Weeks After the Switch | 24 weeks post-switch | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE was determined by the investigator to be related to the drug. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. |
| Number of Participants With One or More SAEs for the Combined Treatment Groups 24 Weeks After the Switch | 24 weeks post-switch | A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. |
| Number of Participants With One or More Drug-related SAEs for the Combined Treatment Groups 24 Weeks After the Switch | 24 weeks post-switch | A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. A drug-related SAE was determined by the investigator to be related to the drug. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. |
| Number of Participants Who Discontinued Treatment Due to an AE for the Combined Treatment Groups 24 Weeks After the Switch | 24 weeks post-switch | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. |
| Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Week 4 | Week 4 | A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach. |
| Change From Baseline in CNS Toxicity Score at Week 4 | Baseline and Week 4 | A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. The CNS toxicity score was calculated by summing across all 10 CNS toxicities and converting the sum to a percentage of the maximum possible sum of intensities (10 x 3 = 30). A positive change from baseline score indicates worsening symptoms. A negative change from baseline score indicates improvement in symptoms. |
| Change From Baseline in CNS Toxicity Score at Week 12 | Baseline and Week 12 | A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. The CNS toxicity score was calculated by summing across all 10 CNS toxicities and converting the sum to a percentage of the maximum possible sum of intensities (10 x 3 = 30). A positive change from baseline score indicates worsening symptoms. A negative change from baseline score indicates improvement in symptoms. |
| Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups | Baseline (time of switch) and 24 weeks post-switch | A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. For the Immediate Switch Group (ISG) time of switch was study Day 1, and week 24 post-switch was week 24. For the Delayed Switch Group (DSG) time of switch was study week 12, and week 24 post-switch was week 36. |
| CNS Toxicity Scores at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups | Baseline (time of switch) and 24 weeks post-switch | A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). The CNS toxicity score was calculated by summing across all 10 CNS toxicities and converting the sum to a percentage of the maximum possible sum of intensities (10 x 3 = 30). A higher CNS score indicates worse symptoms. A positive change in CNS score indicates worsening symptoms. A negative change indicates improvement in symptoms. For the ISG time of switch was study Day 1, and week 24 post-switch was week 24. For the DSG time of switch was study week 12, and week 24 post-switch was week 36. |
| Number of Participants With One or More AEs for the Combined Treatment Groups 24 Weeks After the Switch | 24 weeks post-switch | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. |
| Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups | Baseline (time of switch) and 24 weeks post-switch | Blood was collected under fasting conditions at time of switch and 24 weeks post-switch in order to determine the change from baseline of the following lipids: low-density lipoprotein (LDL) cholesterol; Non high-density lipoprotein (HDL) cholesterol; cholesterol; HDL cholesterol; and triglyceride. For the ISG time of switch was study Day 1, and week 24 post-switch was week 24. For the DSG time of switch was study week 12, and week 24 post-switch was week 36. |
| Percentage of Participants With HIV-1 RNA <50 and <40 Copies/ml at Week 24 Post-switch for the Combined Treatment Groups | 24 weeks post-switch | Blood was collected under fasting conditions at 24 weeks post-switch in order to determine the HIV-1 RNA. For the ISG week 24 post-switch was week 24. For the DSG week 24 post-switch was week 36. |
| Change From Time of Switch to Week 24 Post Switch in CD4 T-cell Count for the Combined Treatment Groups | Baseline (time of switch) and 24 weeks post-switch | Blood was collected at time of switch and at 24 weeks post-switch in order to determine the CD4 T-cell count. For the ISG time of switch was study Day 1, and week 24 post-switch was week 24. For the DSG time of switch was study week 12, and week 24 post-switch was week 36. |
| Number of Participants With One or More Adverse Events (AEs) Through Study Week 12 | Up to Week 12 | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. |
| Number of Participants With One or More Drug-related AEs Through Study Week 12 | Up to Week 12 | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE was determined by the investigator to be related to the drug. |
| Number of Participants With One or More Serious Adverse Events (SAEs) Through Study Week 12 | Up to Week 12 | A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. |
| Number of Participants With One or More Drug-related SAEs Through Study Week 12 | Up to Week 12 | A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. A drug-related SAE was determined by the investigator to be related to the drug. |
| Number of Participants Who Discontinued Treatment Due to an AE Through Study Week 12 | Up to Week 12 | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. |
| Change From Baseline in Fasting Lipids at Week 12 | Baseline (study Day 1) and study week 12 | Blood was collected under fasting conditions on Day 1 and on week 12 in order to determine the concentration of the following lipids: low-density lipoprotein (LDL) cholesterol; Non high-density lipoprotein (HDL) cholesterol; cholesterol; HDL cholesterol; and triglyceride. |
Participant flow
Pre-assignment details
Out of 112 participants screened, 86 were randomized and received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Immediate Switch to MK-1439A Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312). | 43 |
| Deferred Switch to MK-1439A Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324). | 43 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Base Study | Pregnancy | 0 | 1 |
| Base Study | Withdrawal by Subject | 0 | 1 |
| Study Extension 1 (Open-Label) | Adverse Event | 0 | 2 |
| Study Extension 1 (Open-Label) | Availability of study drug locally | 1 | 1 |
| Study Extension 1 (Open-Label) | Lack of Efficacy | 1 | 1 |
| Study Extension 1 (Open-Label) | Pregnancy | 1 | 1 |
| Study Extension 1 (Open-Label) | Withdrawal by Subject | 1 | 2 |
| Study Extension 2 (Open-Label) | Adverse Event | 1 | 0 |
| Study Extension 2 (Open-Label) | Availability of study drug locally | 18 | 13 |
| Study Extension 2 (Open-Label) | Lost to Follow-up | 1 | 0 |
| Study Extension 2 (Open-Label) | Non-Compliance with study drug | 1 | 0 |
| Study Extension 2 (Open-Label) | Pregnancy | 1 | 1 |
| Study Extension 3 (Open-Label) | Physician Decision | 7 | 10 |
| Study Extension 3 (Open-Label) | Pregnancy | 0 | 1 |
Baseline characteristics
| Characteristic | Immediate Switch to MK-1439A | Deferred Switch to MK-1439A | Total |
|---|---|---|---|
| Age, Continuous | 41.8 Years STANDARD_DEVIATION 11.9 | 41.6 Years STANDARD_DEVIATION 11.2 | 41.7 Years STANDARD_DEVIATION 11.5 |
| CNS Toxicity Percentage Of Maximum Score | 32.9 Percentage of maximum score STANDARD_DEVIATION 16.5 | 37.1 Percentage of maximum score STANDARD_DEVIATION 19 | 35.0 Percentage of maximum score STANDARD_DEVIATION 17.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 42 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting Lipids Cholesterol | 178.11 mg/dL STANDARD_DEVIATION 36.39 | 173.02 mg/dL STANDARD_DEVIATION 36.62 | 175.44 mg/dL STANDARD_DEVIATION 36.37 |
| Fasting Lipids HDL Cholesterol | 59.38 mg/dL STANDARD_DEVIATION 14.58 | 55.27 mg/dL STANDARD_DEVIATION 14 | 57.22 mg/dL STANDARD_DEVIATION 14.34 |
| Fasting Lipids LDL Cholesterol | 98.67 mg/dL STANDARD_DEVIATION 35.28 | 99.54 mg/dL STANDARD_DEVIATION 33.57 | 99.13 mg/dL STANDARD_DEVIATION 34.15 |
| Fasting Lipids Non-HDL Cholesterol | 118.73 mg/dL STANDARD_DEVIATION 36.93 | 117.76 mg/dL STANDARD_DEVIATION 37.83 | 118.22 mg/dL STANDARD_DEVIATION 37.16 |
| Fasting Lipids Triglyceride | 107.49 mg/dL STANDARD_DEVIATION 65.64 | 91.39 mg/dL STANDARD_DEVIATION 39.43 | 99.03 mg/dL STANDARD_DEVIATION 53.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 23 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 19 Participants | 31 Participants |
| Sex: Female, Male Female | 19 Participants | 17 Participants | 36 Participants |
| Sex: Female, Male Male | 24 Participants | 26 Participants | 50 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 43 | 0 / 42 | 0 / 43 | 0 / 41 | 0 / 39 | 0 / 33 | 0 / 17 | 0 / 19 |
| other Total, other adverse events | 29 / 43 | 25 / 43 | 26 / 42 | 31 / 43 | 33 / 41 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 43 | 0 / 43 | 1 / 42 | 6 / 43 | 2 / 41 | 3 / 39 | 1 / 33 | 2 / 17 | 0 / 19 |
Outcome results
Primary
Percentage of Participants With at Least One Central Nervous System (CNS) Toxicity of at Least Grade 2 Intensity at Week 12
A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach.
Time frame: Week 12
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch to MK-1439A | Percentage of Participants With at Least One Central Nervous System (CNS) Toxicity of at Least Grade 2 Intensity at Week 12 | 41.9 Percentage of participants |
| Deferred Switch to MK-1439A | Percentage of Participants With at Least One Central Nervous System (CNS) Toxicity of at Least Grade 2 Intensity at Week 12 | 37.2 Percentage of participants |
Comparison: Treatment Difference: Immediate Switch minus Delayed Switchp-value: 0.33195% CI: [-15.92, 24.85]Miettinen and Nurminen
Secondary
Change From Baseline in CNS Toxicity Score at Week 12
A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. The CNS toxicity score was calculated by summing across all 10 CNS toxicities and converting the sum to a percentage of the maximum possible sum of intensities (10 x 3 = 30). A positive change from baseline score indicates worsening symptoms. A negative change from baseline score indicates improvement in symptoms.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Immediate Switch to MK-1439A | Change From Baseline in CNS Toxicity Score at Week 12 | -18.1 Percentage of maximum score |
| Deferred Switch to MK-1439A | Change From Baseline in CNS Toxicity Score at Week 12 | -21.7 Percentage of maximum score |
Comparison: Treatment Difference: Immediate Switch minus Delayed Switch95% CI: [-4.1, 11.3]
Secondary
Change From Baseline in CNS Toxicity Score at Week 4
A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. The CNS toxicity score was calculated by summing across all 10 CNS toxicities and converting the sum to a percentage of the maximum possible sum of intensities (10 x 3 = 30). A positive change from baseline score indicates worsening symptoms. A negative change from baseline score indicates improvement in symptoms.
Time frame: Baseline and Week 4
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Immediate Switch to MK-1439A | Change From Baseline in CNS Toxicity Score at Week 4 | -17.6 Percentage of maximum score |
| Deferred Switch to MK-1439A | Change From Baseline in CNS Toxicity Score at Week 4 | -15.6 Percentage of maximum score |
Comparison: Treatment Difference: Immediate Switch minus Delayed Switch95% CI: [-10.5, 6.5]
Secondary
Change From Baseline in Fasting Lipids at Week 12
Blood was collected under fasting conditions on Day 1 and on week 12 in order to determine the concentration of the following lipids: low-density lipoprotein (LDL) cholesterol; Non high-density lipoprotein (HDL) cholesterol; cholesterol; HDL cholesterol; and triglyceride.
Time frame: Baseline (study Day 1) and study week 12
Population: All randomized participants who received at least one dose of study treatment, and have required lipid data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | Cholesterol | -22.14 mg/dL | Standard Deviation 19.49 |
| Immediate Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | Non-HDL Cholesterol | -14.08 mg/dL | Standard Deviation 17.17 |
| Immediate Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | HDL Cholesterol | -8.05 mg/dL | Standard Deviation 7.74 |
| Immediate Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | Triglyceride | -21.19 mg/dL | Standard Deviation 43.37 |
| Immediate Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | LDL Cholesterol | -10.78 mg/dL | Standard Deviation 15.85 |
| Deferred Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | Triglyceride | 7.10 mg/dL | Standard Deviation 38.55 |
| Deferred Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | LDL Cholesterol | -1.88 mg/dL | Standard Deviation 14.88 |
| Deferred Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | Non-HDL Cholesterol | -0.37 mg/dL | Standard Deviation 16.51 |
| Deferred Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | Cholesterol | 0.00 mg/dL | Standard Deviation 18.04 |
| Deferred Switch to MK-1439A | Change From Baseline in Fasting Lipids at Week 12 | HDL Cholesterol | 0.37 mg/dL | Standard Deviation 7.91 |
Comparison: Difference Estimate: LDL Cholesterol95% CI: [-15.69, -2.35]
Comparison: Difference Estimate: Non-HDL Cholesterol95% CI: [-20.79, -6.35]
Comparison: Difference Estimate: Cholesterol95% CI: [-29.63, -13.21]
Comparison: Difference Estimate: HDL Cholesterol95% CI: [-11.76, -4.6]
Comparison: Difference Estimate: Triglyceride95% CI: [-38.52, -5.84]
Secondary
Change From Time of Switch to Week 24 Post Switch in CD4 T-cell Count for the Combined Treatment Groups
Blood was collected at time of switch and at 24 weeks post-switch in order to determine the CD4 T-cell count. For the ISG time of switch was study Day 1, and week 24 post-switch was week 24. For the DSG time of switch was study week 12, and week 24 post-switch was week 36.
Time frame: Baseline (time of switch) and 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have required CD4 T-cell data. Based on the protocol-specified plan, the combined treatment groups was analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Immediate Switch to MK-1439A | Change From Time of Switch to Week 24 Post Switch in CD4 T-cell Count for the Combined Treatment Groups | 70.4 cells/mm^3 |
Secondary
Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups
Blood was collected under fasting conditions at time of switch and 24 weeks post-switch in order to determine the change from baseline of the following lipids: low-density lipoprotein (LDL) cholesterol; Non high-density lipoprotein (HDL) cholesterol; cholesterol; HDL cholesterol; and triglyceride. For the ISG time of switch was study Day 1, and week 24 post-switch was week 24. For the DSG time of switch was study week 12, and week 24 post-switch was week 36.
Time frame: Baseline (time of switch) and 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have required lipid data. Based on the protocol-specified plan, the combined treatment groups was analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Switch to MK-1439A | Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups | LDL Cholesterol | -10.97 mg/dL | Standard Deviation 17.15 |
| Immediate Switch to MK-1439A | Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups | Non-HDL Cholesterol | -13.18 mg/dL | Standard Deviation 19.82 |
| Immediate Switch to MK-1439A | Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups | Cholesterol | -20.91 mg/dL | Standard Deviation 20.19 |
| Immediate Switch to MK-1439A | Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups | HDL Cholesterol | -7.72 mg/dL | Standard Deviation 9.53 |
| Immediate Switch to MK-1439A | Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups | Triglyceride | -12.99 mg/dL | Standard Deviation 46.61 |
Secondary
CNS Toxicity Scores at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups
A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). The CNS toxicity score was calculated by summing across all 10 CNS toxicities and converting the sum to a percentage of the maximum possible sum of intensities (10 x 3 = 30). A higher CNS score indicates worse symptoms. A positive change in CNS score indicates worsening symptoms. A negative change indicates improvement in symptoms. For the ISG time of switch was study Day 1, and week 24 post-switch was week 24. For the DSG time of switch was study week 12, and week 24 post-switch was week 36.
Time frame: Baseline (time of switch) and 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Immediate Switch to MK-1439A | CNS Toxicity Scores at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups | 24.2 Percentage of maximum score |
| Deferred Switch to MK-1439A | CNS Toxicity Scores at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups | 10.7 Percentage of maximum score |
Comparison: Change from time of switch to 24 weeks post-switch: Treatment difference in score95% CI: [-16.8, -10.1]
Secondary
Number of Participants Who Discontinued Treatment Due to an AE for the Combined Treatment Groups 24 Weeks After the Switch
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36.
Time frame: 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants Who Discontinued Treatment Due to an AE for the Combined Treatment Groups 24 Weeks After the Switch | 0 Participants |
Secondary
Number of Participants Who Discontinued Treatment Due to an AE Through Study Week 12
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to Week 12
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants Who Discontinued Treatment Due to an AE Through Study Week 12 | 0 Participants |
| Deferred Switch to MK-1439A | Number of Participants Who Discontinued Treatment Due to an AE Through Study Week 12 | 0 Participants |
Secondary
Number of Participants With One or More Adverse Events (AEs) Through Study Week 12
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to Week 12
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants With One or More Adverse Events (AEs) Through Study Week 12 | 34 Participants |
| Deferred Switch to MK-1439A | Number of Participants With One or More Adverse Events (AEs) Through Study Week 12 | 34 Participants |
Secondary
Number of Participants With One or More AEs for the Combined Treatment Groups 24 Weeks After the Switch
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36.
Time frame: 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants With One or More AEs for the Combined Treatment Groups 24 Weeks After the Switch | 71 Participants |
Secondary
Number of Participants With One or More Drug-related AEs for the Combined Treatment Groups 24 Weeks After the Switch
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE was determined by the investigator to be related to the drug. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36.
Time frame: 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants With One or More Drug-related AEs for the Combined Treatment Groups 24 Weeks After the Switch | 18 Participants |
Secondary
Number of Participants With One or More Drug-related AEs Through Study Week 12
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE was determined by the investigator to be related to the drug.
Time frame: Up to Week 12
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants With One or More Drug-related AEs Through Study Week 12 | 14 Participants |
| Deferred Switch to MK-1439A | Number of Participants With One or More Drug-related AEs Through Study Week 12 | 9 Participants |
Secondary
Number of Participants With One or More Drug-related SAEs for the Combined Treatment Groups 24 Weeks After the Switch
A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. A drug-related SAE was determined by the investigator to be related to the drug. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36.
Time frame: 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants With One or More Drug-related SAEs for the Combined Treatment Groups 24 Weeks After the Switch | 0 Participants |
Secondary
Number of Participants With One or More Drug-related SAEs Through Study Week 12
A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. A drug-related SAE was determined by the investigator to be related to the drug.
Time frame: Up to Week 12
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants With One or More Drug-related SAEs Through Study Week 12 | 0 Participants |
| Deferred Switch to MK-1439A | Number of Participants With One or More Drug-related SAEs Through Study Week 12 | 0 Participants |
Secondary
Number of Participants With One or More SAEs for the Combined Treatment Groups 24 Weeks After the Switch
A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36.
Time frame: 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants With One or More SAEs for the Combined Treatment Groups 24 Weeks After the Switch | 1 Participants |
Secondary
Number of Participants With One or More Serious Adverse Events (SAEs) Through Study Week 12
A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose.
Time frame: Up to Week 12
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immediate Switch to MK-1439A | Number of Participants With One or More Serious Adverse Events (SAEs) Through Study Week 12 | 0 Participants |
| Deferred Switch to MK-1439A | Number of Participants With One or More Serious Adverse Events (SAEs) Through Study Week 12 | 0 Participants |
Secondary
Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups
A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. For the Immediate Switch Group (ISG) time of switch was study Day 1, and week 24 post-switch was week 24. For the Delayed Switch Group (DSG) time of switch was study week 12, and week 24 post-switch was week 36.
Time frame: Baseline (time of switch) and 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch to MK-1439A | Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups | 68.6 Percentage of participants |
| Deferred Switch to MK-1439A | Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups | 30.2 Percentage of participants |
Comparison: Change from time of switch to 24 weeks post-switch: Treatment difference in percent response95% CI: [-51.2, -23.8]
Secondary
Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Week 4
A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach.
Time frame: Week 4
Population: All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch to MK-1439A | Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Week 4 | 46.5 Percentage of participants |
| Deferred Switch to MK-1439A | Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Week 4 | 65.1 Percentage of participants |
Comparison: Treatment Difference: Immediate Switch minus Delayed Switch95% CI: [-38.14, 2.51]
Secondary
Percentage of Participants With HIV-1 RNA <50 and <40 Copies/ml at Week 24 Post-switch for the Combined Treatment Groups
Blood was collected under fasting conditions at 24 weeks post-switch in order to determine the HIV-1 RNA. For the ISG week 24 post-switch was week 24. For the DSG week 24 post-switch was week 36.
Time frame: 24 weeks post-switch
Population: All randomized participants who received at least one dose of study treatment, and have required HIV-1 RNA data. Based on the protocol-specified plan, the combined treatment groups was analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immediate Switch to MK-1439A | Percentage of Participants With HIV-1 RNA <50 and <40 Copies/ml at Week 24 Post-switch for the Combined Treatment Groups | < 50 copies/mL | 95.3 Percentage of participants |
| Immediate Switch to MK-1439A | Percentage of Participants With HIV-1 RNA <50 and <40 Copies/ml at Week 24 Post-switch for the Combined Treatment Groups | < 40 copies/mL | 95.3 Percentage of participants |