HIV-1 Infection
Conditions
Brief summary
The multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to MK-1439A (MK-1439 \[doravirine\] plus lamivudine and tenofovir disoproxil fumarate) in HIV-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) \<50 copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.
Detailed description
Three optional study extensions are planned. Study Extension 1 will evaluate safety of the switch to doravirine, tenofovir, lamivudine for an additional 2 years beyond the Base Study. Study Extensions 2 and 3 will evaluate safety of the switch to doravirine, tenofovir, lamivudine until doravirine, tenofovir, lamivudine becomes locally available, or 4 years beyond Study Extension 1, whichever comes first.
Interventions
Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg
DRUGBaseline regimen of ritonavir- or cobicistat-boosted protease inhibitor
Baseline regimen of antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) administered according to the product circular
DRUGBaseline regimen of cobicistat-boosted elvitegravir
Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular
DRUGBaseline regimen of a non-nucleoside reverse transcriptase inhibitor
Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular
DRUGBaseline regimen of two nucleoside reverse transcriptase inhibitors
Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria include, but are not limited to: * Have plasma Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) levels below the limit of quantification (BLoQ) (\<40 copies/mL by the Abbott RealTime HIV-1 Assay as determined by the central laboratory) at the screening visit. * Receiving antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 Nucleoside Reverse Transcriptase Inhibitor (NRTIs) (and no other antiretroviral therapy) continuously for \>= 6 months. * Receiving first or second retroviral regimen (participants receiving a NNRTI at Screening must be on their first retroviral regimen) * No history of using an experimental NNRTI * Has a genotype prior to starting his/her initial antiretroviral regimen and no known resistance to any of the study agents * Not receiving lipid lowering therapy or on a stable dose of lipid lowering therapy at the time of enrollment * Has the following laboratory values at screening within 30 days prior to the treatment phase of this study: Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN), Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 5.0 x ULN, and Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male) * Has a calculated creatinine clearance at the time of screening ≥ 50 mL/min, based on the Cockcroft-Gault equation * Male or female participant not of reproductive potential or, if of reproductive potential, agrees to avoid becoming pregnant or impregnating a partner while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: 1) practice abstinence from heterosexual activity, or 2) use acceptable contraception during heterosexual activity * For inclusion in Study Extension 1 (optional): completed the Week 48 visit; considered to have derived benefit from study participation up to Week 48; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug * For inclusion in Study Extension 2 (optional): completed the Week 144 visit; considered to have derived benefit from study participation up to Week 144; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug * For inclusion in Study Extension 3 (optional): completed the Week 240 visit; considered to have derived benefit from study participation up to Week 240; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL | Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24 | The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach and all missing data were considered treatment failures, regardless of the reason. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | Baseline and Week 24 | To evaluate the effect on fasting LDL-C of an immediate switch to DOR/3TC/TDF on Study Day 1 compared with continuation of a ritonavir-boosted, PI-based regimen, as measured by mean change from baseline in each treatment group. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Baseline and Week 24 | Serum non-HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid lowering therapy. |
| Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL | Week 24 | The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach and all missing data were considered treatment failures, regardless of the reason. |
| Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Immediate Switch to MK-1439A arm: Baseline and Week 48; Delayed Switch to MK-1439A arm: Baseline and Week 24 | The mean change from baseline in CD4 cell counts was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued due to lack of efficacy. Cell counts were measured and expressed as cells/mm\^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay. |
| Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE) | Up to 24 weeks | A serious adverse event is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants with any SAE was assessed. |
| Percentage of Participants With HIV-1 RNA >=50 Copies/mL | Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24 | The percentage of participants in each arm achieving HIV-1 RNA levels \>=50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach. |
| Percentage of Participants Experiencing ≥1 Adverse Event (AE) | Up to week 24 | An AE is defined as 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. |
| Percentage of Participants Discontinuing From Study Medication Due to an AE(s) | Up to Week 24 | An AE is defined as 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. |
| Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL | Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24 | The percentage of participants in each arm achieving HIV-1 RNA levels \<40 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach and all missing data were considered treatment failures, regardless of the reason. |
Participant flow
Pre-assignment details
Out of 852 participants screened, 673 were randomized to study treatment, and 670 were treated. There were 122 global study sites utilized.
Participants by arm
| Arm | Count |
|---|---|
| Immediate Switch Group (ISG) Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for \>=6 months with undetectable HIV-1 RNA switched on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions. | 450 |
| Delayed Switch Group (DSG) Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA continued on this therapy until Week 24, at which time they switched to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions. | 223 |
| Total | 673 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Day 1 to Week 24 | Adverse Event | 7 | 1 |
| Day 1 to Week 24 | Death | 1 | 0 |
| Day 1 to Week 24 | Lack of Efficacy | 0 | 1 |
| Day 1 to Week 24 | Lost to Follow-up | 3 | 4 |
| Day 1 to Week 24 | Physician Decision | 2 | 3 |
| Day 1 to Week 24 | Protocol Violation | 1 | 4 |
| Day 1 to Week 24 | Randomized, not treated | 3 | 0 |
| Day 1 to Week 24 | Withdrawal by Subject | 6 | 1 |
| Study Extension 1 | Adverse Event | 7 | 5 |
| Study Extension 1 | Death | 1 | 0 |
| Study Extension 1 | Lack of Efficacy | 2 | 5 |
| Study Extension 1 | Lost to Follow-up | 2 | 3 |
| Study Extension 1 | Non-compliance with study drug | 3 | 0 |
| Study Extension 1 | Physician Decision | 4 | 2 |
| Study Extension 1 | Pregnancy | 1 | 0 |
| Study Extension 1 | Protocol Violation | 0 | 1 |
| Study Extension 1 | Withdrawal by Subject | 21 | 7 |
| Study Extension 2 | Adverse Event | 3 | 3 |
| Study Extension 2 | Availability of study medication locally | 152 | 64 |
| Study Extension 2 | Death | 2 | 0 |
| Study Extension 2 | Lack of Efficacy | 1 | 0 |
| Study Extension 2 | Lost to Follow-up | 2 | 1 |
| Study Extension 2 | Non-compliance with study drug | 1 | 0 |
| Study Extension 2 | Physician Decision | 2 | 5 |
| Study Extension 2 | Pregnancy | 1 | 0 |
| Study Extension 2 | Withdrawal by Subject | 10 | 3 |
| Study Extension 3 | Adverse Event | 1 | 0 |
| Study Extension 3 | Availability of study medication locally | 11 | 3 |
| Study Extension 3 | Lost to Follow-up | 1 | 0 |
| Study Extension 3 | Withdrawal by Subject | 2 | 1 |
| Week 24 to Week 48 | Adverse Event | 6 | 2 |
| Week 24 to Week 48 | Lack of Efficacy | 5 | 1 |
| Week 24 to Week 48 | Lost to Follow-up | 2 | 0 |
| Week 24 to Week 48 | Non-Compliance With Study Drug | 0 | 1 |
| Week 24 to Week 48 | Physician Decision | 2 | 1 |
| Week 24 to Week 48 | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Delayed Switch Group (DSG) | Total | Immediate Switch Group (ISG) |
|---|---|---|---|
| Age, Continuous | 43.7 Years STANDARD_DEVIATION 10.6 | 43.3 Years STANDARD_DEVIATION 10.3 | 43.1 Years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants | 141 Participants | 98 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 177 Participants | 524 Participants | 347 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 25 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 90 Participants | 56 Participants |
| Race (NIH/OMB) More than one race | 11 Participants | 36 Participants | 25 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 168 Participants | 514 Participants | 346 Participants |
| Sex: Female, Male Female | 29 Participants | 104 Participants | 75 Participants |
| Sex: Female, Male Male | 194 Participants | 569 Participants | 375 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 | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 450 | 0 / 223 | 0 / 427 | 0 / 209 | 1 / 398 | 0 / 202 | 3 / 303 | 0 / 154 | 0 / 84 | 0 / 43 |
| other Total, other adverse events | 100 / 447 | 28 / 223 | 63 / 427 | 33 / 209 | 107 / 398 | 57 / 202 | 24 / 303 | 11 / 154 | 9 / 84 | 3 / 43 |
| serious Total, serious adverse events | 13 / 447 | 8 / 223 | 11 / 427 | 4 / 209 | 37 / 398 | 13 / 202 | 13 / 303 | 7 / 154 | 3 / 84 | 1 / 43 |
Outcome results
Primary
Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL
The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach and all missing data were considered treatment failures, regardless of the reason.
Time frame: Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch Group (ISG) | Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL | 90.8 Percentage of Participants |
| Delayed Switch Group (DSG) | Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL | 94.6 Percentage of Participants |
95% CI: [-7.877, 0.31]
Secondary
Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts
The mean change from baseline in CD4 cell counts at Week 48 was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued due to lack of efficacy. Cell counts were measured and expressed as cells/mm\^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
Time frame: Baseline and Week 24
Population: All randomized participants who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Switch Group (ISG) | Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Baseline | 664.5 cells/mm^3 | Standard Deviation 300.7 |
| Immediate Switch Group (ISG) | Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Change from Baseline | 5.1 cells/mm^3 | Standard Deviation 174.9 |
| Delayed Switch Group (DSG) | Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Baseline | 655.6 cells/mm^3 | Standard Deviation 279.3 |
| Delayed Switch Group (DSG) | Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Change from Baseline | 18.0 cells/mm^3 | Standard Deviation 157.7 |
95% CI: [-41.1, 15.4]
Secondary
Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts
The mean change from baseline in CD4 cell counts was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued due to lack of efficacy. Cell counts were measured and expressed as cells/mm\^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
Time frame: Immediate Switch to MK-1439A arm: Baseline and Week 48; Delayed Switch to MK-1439A arm: Baseline and Week 24
Population: All randomized participants who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Switch Group (ISG) | Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Baseline | 660.5 cells/mm^3 | Standard Deviation 293.4 |
| Immediate Switch Group (ISG) | Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Change from Baseline | 13.9 cells/mm^3 | Standard Deviation 168.1 |
| Delayed Switch Group (DSG) | Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Baseline | 655.6 cells/mm^3 | Standard Deviation 279.3 |
| Delayed Switch Group (DSG) | Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts | Change from Baseline | 18.0 cells/mm^3 | Standard Deviation 157.7 |
95% CI: [-31.6, 23.5]
Secondary
Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C)
To evaluate the effect on fasting LDL-C of an immediate switch to DOR/3TC/TDF on Study Day 1 compared with continuation of a ritonavir-boosted, PI-based regimen, as measured by mean change from baseline in each treatment group. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Time frame: Baseline and Week 24
Population: All randomized participants in the ritonavir-boosted PI-based regimen who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Switch Group (ISG) | Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | Baseline | 108.82 mg/dL | Standard Deviation 34.21 |
| Immediate Switch Group (ISG) | Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | Change from Baseline | -16.54 mg/dL | Standard Deviation 23.1 |
| Delayed Switch Group (DSG) | Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | Baseline | 109.00 mg/dL | Standard Deviation 33.58 |
| Delayed Switch Group (DSG) | Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | Change from Baseline | -1.94 mg/dL | Standard Deviation 25.74 |
p-value: <0.000195% CI: [-18.92, -10.38]ANCOVA
Secondary
Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Serum non-HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid lowering therapy.
Time frame: Baseline and Week 24
Population: All randomized participants who received the ritonavir-boosted PI-based regimen at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Switch Group (ISG) | Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Baseline | 139.14 mg/dL | Standard Deviation 42.12 |
| Immediate Switch Group (ISG) | Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Change from Baseline | -24.74 mg/dL | Standard Deviation 29.26 |
| Delayed Switch Group (DSG) | Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Baseline | 137.99 mg/dL | Standard Deviation 38.46 |
| Delayed Switch Group (DSG) | Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Change from Baseline | -1.31 mg/dL | Standard Deviation 28.45 |
p-value: <0.000195% CI: [-28, -18.05]ANCOVA
Secondary
Percentage of Participants Discontinuing From Study Medication Due to an AE(s)
An AE is defined as 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.
Time frame: Up to Week 24
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch Group (ISG) | Percentage of Participants Discontinuing From Study Medication Due to an AE(s) | 2.5 Percentage of Participants |
| Delayed Switch Group (DSG) | Percentage of Participants Discontinuing From Study Medication Due to an AE(s) | 0.4 Percentage of Participants |
Secondary
Percentage of Participants Experiencing ≥1 Adverse Event (AE)
An AE is defined as 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.
Time frame: Up to week 24
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch Group (ISG) | Percentage of Participants Experiencing ≥1 Adverse Event (AE) | 68.9 Percentage of Participants |
| Delayed Switch Group (DSG) | Percentage of Participants Experiencing ≥1 Adverse Event (AE) | 52.5 Percentage of Participants |
Secondary
Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)
A serious adverse event is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants with any SAE was assessed.
Time frame: Up to 24 weeks
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch Group (ISG) | Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE) | 2.9 Percentage of Participants |
| Delayed Switch Group (DSG) | Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE) | 3.6 Percentage of Participants |
Secondary
Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL
The percentage of participants in each arm achieving HIV-1 RNA levels \<40 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach and all missing data were considered treatment failures, regardless of the reason.
Time frame: Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch Group (ISG) | Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL | 89.7 Percentage of Participants |
| Delayed Switch Group (DSG) | Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL | 93.3 Percentage of Participants |
95% CI: [-7.977, 0.864]
Secondary
Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL
To evaluate the immunological effect of an immediate switch to MK -1439A on Study Day 1 compared with continuation of a ritonavir boosted, PI-based regimen, as measured by the proportion of subjects maintaining HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 Assay (\<40 copies/mL) in both treatment groups.
Time frame: Immediate Switch to MK-1439A arm: Week 24; Delayed Switch to MK-1439A arm: Week 24
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch Group (ISG) | Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL | 92.8 Percentage of Participants |
| Delayed Switch Group (DSG) | Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL | 93.3 Percentage of Participants |
95% CI: [-4.591, 3.738]
Secondary
Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL
The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach and all missing data were considered treatment failures, regardless of the reason.
Time frame: Week 24
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch Group (ISG) | Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL | 93.7 Percentage of Participants |
| Delayed Switch Group (DSG) | Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL | 94.6 Percentage of Participants |
95% CI: [-4.706, 2.952]
Secondary
Percentage of Participants With HIV-1 RNA >=50 Copies/mL
The percentage of participants in each arm achieving HIV-1 RNA levels \>=50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach.
Time frame: Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Switch Group (ISG) | Percentage of Participants With HIV-1 RNA >=50 Copies/mL | 1.6 Percentage of Participants |
| Delayed Switch Group (DSG) | Percentage of Participants With HIV-1 RNA >=50 Copies/mL | 1.8 Percentage of Participants |
95% CI: [-2.529, 2.064]