HIV Infections
Conditions
Keywords
HIV-Associated Neurocognitive Disorder
Brief summary
People infected with HIV often have cognitive dysfunction even if they are on antiretroviral therapy (ART) and have undetectable viral loads. The study evaluated if the addition of maraviroc (MVC) and dolutegravir (DTG) (which are two antiretroviral \[ARV\] medications) to participants' existing ART regimens improved participants' neurocognitive performance.
Detailed description
HIV-infected people often have cognitive dysfunction (HIV-associated neurocognitive disorder, or HAND), which includes asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD), even if they are on ART and have undetectable viral loads. In this study, researchers evaluated the effectiveness of adding MVC and DTG to the current ART regimen of HIV-infected people with undetectable (\<50 copies/mL) plasma HIV-1 RNA who had neurocognitive impairment and who had been on stable ART for at least 6 months prior to study entry. The purpose of this study was to evaluate if the addition of MVC and DTG to participants' existing ART regimens improved participants' neurocognitive performance. Participants were randomly assigned to one of three arms. All participants remained on their existing ART regimens; they took their assigned study drugs in addition to their ART regimen. Study visits occurred at entry and Weeks 2, 4, 12, 24, 48, 72, and 96. Visits may have included physical examinations, blood collection, neurocognitive testing, pregnancy testing, and questionnaires. Some participants may have had an optional lumbar puncture procedure at study entry and Week 48. Participants returned for refills of study drugs on Weeks 36, 60, and 84.
Interventions
DRUGPlacebo for maraviroc (MVC)
Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen
DRUGPlacebo for dolutegravir (DTG)
Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen
Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen
DRUGMaraviroc (MVC)
Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection, documented by: * a licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. NOTE: The term licensed refers to a United States Food and Drug Administration (FDA)-approved kit, which is required for all IND studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA. OR * Documentation of HIV diagnosis in the medical record by a healthcare provider. * On current ART for at least 6 months prior to study entry with no interruption in treatment of greater than or equal to 7 consecutive days. Note: The following ART changes are allowed: * Tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF)/TAF-containing fixed-dose combination regimens * Ritonavir (RTV) to cobicistat (COBI)/COBI-containing fixed-dose combination regimens * No plans to change ART while on study. Note: The following planned ART changes are allowed: * TDF to TAF/TAF-containing fixed-dose combination regimens * RTV to COBI/COBI-containing fixed-dose combination regimens * HIV-1 plasma RNA less than 50 copies/mL obtained within 90 days prior to study entry by any FDA-approved assay at any United States laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs. * No more than one HIV-1 plasma RNA greater than or equal to 50 and less than 200 copies/mL (only one blip) in the past 6 months with a subsequent HIV-1 plasma RNA less than 50 copies/mL. NOTE: There should be no plasma HIV-1 RNA greater than 200 copies/mL within the 6 months prior to study entry. * HAND diagnosis (ANI, MND, or HAD) within 60 days prior to study entry. HAND is defined as at least mild impairment on neurocognitive testing (more than one standard deviation below appropriate normative data in two domains of functioning) and no severely confounding factors. * Screening laboratory values obtained within 60 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs: * Absolute neutrophil count (ANC) greater than or equal to 500/mm\^3 * Hemoglobin greater than or equal to 7.5 g/dL * Platelet count greater than or equal to 40,000/mm\^3 * Creatinine less than or equal to 2.0 x upper limit of normal (ULN) * Aspartate transaminase (AST) less than or equal to 5 x ULN * Alanine transaminase (ALT) less than 3 x ULN * Alkaline phosphatase less than or equal to 5 x ULN * Total bilirubin less than 1.5 x ULN. NOTE: If the potential participant is taking an indinavir (IDV)- or atazanavir (ATV)-containing regimen at the time of screening, total bilirubin less than or equal to 5 x ULN is acceptable. * Creatinine clearance (CrCl) greater than or equal to 60 mL/min, either measured or estimated by Cockcroft-Gault equation. NOTE: A calculator for estimating the CrCl can be found at www.fstrf.org/ACTG/ccc.html * Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, hysterectomy or bilateral salpingectomy or bilateral oophorectomy or tubal ligation) must have a negative serum or urine pregnancy test by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC) / CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs within 48 hours prior to study entry * Females of reproductive potential must agree not to participate in the conception process (ie, active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, must use at least one reliable form of contraception. Female participants must use contraceptives while receiving study treatment and for 6 weeks after stopping study treatment. More information on this criterion is available in the protocol. * Ability and willingness of participant to complete the neuropsychological tests * Ability and willingness of participant or a legally authorized representative (see protocol for more information) to provide informed consent * Ability and willingness to take oral study medications
Exclusion criteria
* Current or past medical condition(s) that in the opinion of the investigator prevents attribution of the cause of cognitive impairment to HIV. For example: * Major depressive disorder with psychotic features * Traumatic Brain Injury (TBI) with a clear impact on activities of daily living * Developmental delay, intellectual deficit, and/or severe educational disability resulting in some dependence for activities of daily living * Ongoing substance use disorder with significant impact on activities of daily living. Difficult or impossible to determine whether cognitive or functional decline is due to substance use or HIV, or both * Evidence of intoxication or withdrawal during the screening evaluation * Central nervous system (CNS) infections or opportunistic conditions: brain abscess (bacterial, mycobacterial, fungal or Toxoplasma), meningitis with persistent neurologic impairment, primary CNS lymphoma, progressive multifocal leukoencephalopathy (PML), or another structural brain lesion with neurological sequelae * Other CNS conditions: non-opportunistic primary or metastatic brain tumors, uncontrolled seizure disorder, progressive multiple sclerosis, stroke with neurological sequelae, or dementia due to causes other than HIV (eg, Alzheimer's disease) * Constitutional illness (eg, persistent unexplained fever, diarrhea, significant weight loss, disabling weakness) within 30 days of screening * Known untreated B12 deficiency or malnutrition (body mass index \[BMI\] less than 18) at screening * Evidence of current hepatitis C virus infection (HCV) (ie, HCV antibody \[Ab\] positive within 90 days prior to study entry unless also shown to be plasma HCV RNA negative within the same time period) * Unstable and advanced liver disease (as defined by the presence of at least one of the following: ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice) * Prior or current use of any CCR5 antagonist (such as MVC and cenicriviroc \[CVC\]) and integrase inhibitor (such as RAL, DTG, and elvitegravir \[EVG\]) * Current use of any medication, including antiretrovirals, prohibited in the study (refer to the A5324 protocol-specific web page \[PSWP\] for the prohibited medications) * Breastfeeding * Presence of an AIDS-defining opportunistic infection within 6 months prior to entry. Note: Refer to the A5324 Manual of Operations (MOPS) for the list of AIDS-defining opportunistic infections. * Active syphilis or treatment for syphilis within 90 days prior to study entry. NOTE: Active syphilis is defined as four-fold increase in serum rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL) tests in an individual with past syphilis, or newly reactive serum RPR or VDRL with a reactive confirmatory test (enzyme immunoassays \[EIA\] or chemiluminescent assay \[CIA\], T. pallidum particle agglutination \[TP-PA\], or fluorescent treponemal antibody absorbed \[FTA-ABS\]). * Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Normalized Composite Neurocognitive Test Score at Week 48 From Baseline | Measured at Baseline and Week 48 | The normalized composite neurocognitive test score (total z-score) was defined as the average of the z-scores from the following tests: Domestic (US-based) and International Participants: * Grooved pegboard dominant * Grooved pegboard non-dominant * Hopkins Verbal Learning Test (HVLT-R) Learning trials * HVLT-R Delayed recall * HVLT-R Delayed recognition * Semantic verbal fluency Domestic only: * Stroop color naming * Stroop word reading * Stroop interference trial * Letter fluency * Trail Making A * Trail Making B * WAIS-III Symbol search * Digit Symbol International only: * Timed Gait * Finger Tapping Dominant * Finger Tapping Non-dominant * Color Trail 1 Z-scores were calculated using a demographically appropriate norming process. Higher z-scores correspond with better neurocognitive performance. Change was calculated as the total z-score at Week 48 minus the total z-score at Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CD8+ T-cell Count | Measured at Baseline and Weeks 24, 48, and 96 | Changes in CD8+ T-cell count were calculated as the CD8+ T-cell count at a given time point minus the CD8+ T-cell count at baseline. |
| Change in Log10 IP-10 in CSF at Week 48 From Baseline | Measured at Baseline and Week 48 | Changes in Log10 IP-10 in CSF were calculated as the Log10 IP-10 in CSF at Week 48 minus the Log10 IP-10 in CSF at Baseline. |
| Change in Log10 Neopterin in CSF at Week 48 From Baseline | Measured at Baseline and Week 48 | Changes in Log10 Neopterin in CSF were calculated as the Log10 Neopterin in CSF at Week 48 minus the Log10 Neopterin in CSF at Baseline. |
| Change in Log10 NFL in CSF at Week 48 From Baseline | Measured at Baseline and Week 48 | Changes in Log10 NFL in CSF were calculated as the Log10 NFL in CSF at Week 48 minus the Log10 NFL in CSF at Baseline. |
| Number of Participants With Treatment Related Adverse Events (AEs) | Measured from treatment initiation through Week 96 | Treatment Related Adverse Events were determined by the study sites indicating a relationship between an adverse event and the study treatment. |
| Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Measured at Baseline and Weeks 24, 72, and 96 | The normalized composite neurocognitive test score (total z-score) was defined as the average of the z-scores from the following tests: Domestic and International Participants: * Grooved pegboard dominant * Grooved pegboard non-dominant * HVLT-R Learning trials * HVLT-R Delayed recall * HVLT-R Delayed recognition * Semantic verbal fluency Domestic only: * Stroop color naming * Stroop word reading * Stroop interference trial * Letter fluency * Trail Making A * Trail Making B * WAIS-III Symbol search * Digit Symbol International only: * Timed Gait * Finger Tapping Dominant * Finger Tapping Non-dominant * Color Trail 1 * Color Trail 2 Z-scores were calculated using a demographically appropriate norming process. Higher z-scores correspond with better neurocognitive performance. Change was calculated as the total z-score at the given time point minus the total z-score at Baseline. |
| Change in Functional Status Scores | Measured at Baseline and Weeks 24, 48, 72, and 96 | Functional status scores were calculated based on the instrumental activities of daily living (IADLs) forms. IADL scores were calculated as the sum of the eight IADL tasks where the task scores were equal to 1 if a participant did not need assistance with the task and equal to 0 if a participant needed some level of help with the task. The maximum possible functional status score was 8, while the minimum possible functional status score was 0, with higher functional status scores indicating a higher level of functionality. |
| Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | Measured at Weeks 24, 48, and 96 | The number of participants with Plasma HIV-1 RNA greater than or equal to 50 copies/mL was assessed at each given time point. |
| CD4+ T-cell Counts | Measured at Weeks 24, 48, and 96 | CD4+ T-cell counts were recorded at the given time point |
| Change in CD4+ T-cell Count | Measured at Baseline and Weeks 24, 48, and 96 | Changes in CD4+ T-cell count were calculated as the CD4+ T-cell count at a given time point minus the CD4+ T-cell count at Baseline. |
| CD8+ T-cell Counts | Measured at Weeks 24, 48, and 96 | CD8+ T-cell counts were recorded at the given time point |
| Change in Log10 sCD14 in Plasma at Week 48 From Baseline | Measured at Baseline and Week 48 | Changes in Log10 sCD14 in Plasma were calculated as the Log10 sCD14 in Plasma at Week 48 minus the Log10 sCD14 in Plasma at Baseline. |
| Change in Log10 MIP-1 Beta in Plasma at Week 48 From Baseline | Measured at Baseline and Week 48 | Changes in Log10 MIP-1 Beta in Plasma were calculated as the Log10 MIP-1 Beta in Plasma at Week 48 minus the Log10 MIP-1 Beta in Plasma at Baseline. Results below the lower limit of quantification were set to the lower limit value of 11. |
| Change in Log10 sTNFr-II in Plasma at Week 48 From Baseline | Measured at Baseline and Week 48 | Changes in Log10 sTNFr-II in Plasma were calculated as the Log10 sTNFr-II in Plasma at Week 48 minus the Log10 sTNFr-II in Plasma at Baseline. |
| Change in Log10 VCAM in Plasma at Week 48 From Baseline | Measured at Baseline and Week 48 | Changes in Log10 VCAM in Plasma were calculated as the Log10 VCAM in Plasma at Week 48 minus the Log10 VCAM in Plasma at Baseline. |
| Change in Log10 MIP-1 Beta in Cerebrospinal Fluid (CSF) at Week 48 From Baseline | Measured at Baseline and Week 48 | Changes in Log10 MIP-1 Beta in CSF were calculated as the Log10 MIP-1 Beta in CSF at Week 48 minus the Log10 MIP-1 Beta in CSF at Baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Residual Viremia | Measured at Baseline and Week 48 | This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome due to lack of funding for testing. |
| Changes in T Cell and Monocyte Activation | Measured at Baseline and Week 48 | This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome due to lack of funding for testing. |
| Changes in Cell-associated HIV-1 RNA/DNA/2-long Terminal Repeat Sequences (LTR) Circles and Single Copy Assay (SCA) | Measured at Baseline and Week 48 | This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome due to lack of funding for testing. |
Countries
Brazil, Puerto Rico, South Africa, Thailand, United States
Participant flow
Recruitment details
Participants were enrolled at 30 Clinical Research Sites (CRSs) in the United States, Thailand, Brazil, and South Africa between April 2016 and November 2018.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Placebo MVC and Placebo DTG In addition to their existing ART regimens, participants in Arm A received placebo for MVC and placebo for DTG.
Placebo for maraviroc (MVC): Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen
Placebo for dolutegravir (DTG): Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen | 63 |
| Arm B: DTG and Placebo MVC In addition to their existing ART regimens, participants in Arm B received DTG and placebo for MVC.
Placebo for maraviroc (MVC): Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen
Dolutegravir (DTG): Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen | 67 |
| Arm C: MVC and DTG In addition to their existing ART regimens, participants in Arm C received MVC and DTG
Dolutegravir (DTG): Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen
Maraviroc (MVC): Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen | 61 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 4 | 2 |
| Overall Study | Not able to get to clinic | 1 | 2 | 1 |
| Overall Study | Severe Debilitation | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | Arm A: Placebo MVC and Placebo DTG | Arm B: DTG and Placebo MVC | Arm C: MVC and DTG | Total |
|---|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 7 | 52 years STANDARD_DEVIATION 9 | 52 years STANDARD_DEVIATION 8 | 52 years STANDARD_DEVIATION 8 |
| CD4 Cell Count | 681 cells/mm^3 STANDARD_DEVIATION 294 | 703 cells/mm^3 STANDARD_DEVIATION 278 | 726 cells/mm^3 STANDARD_DEVIATION 331 | 703 cells/mm^3 STANDARD_DEVIATION 300 |
| CD8 Cell Count | 789 cells/mm^3 STANDARD_DEVIATION 334 | 809 cells/mm^3 STANDARD_DEVIATION 393 | 816 cells/mm^3 STANDARD_DEVIATION 393 | 805 cells/mm^3 STANDARD_DEVIATION 373 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 17 Participants | 10 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 50 Participants | 51 Participants | 149 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HIV RNA <50 copies/mL | 62 Participants | 64 Participants | 58 Participants | 184 Participants |
| HIV RNA ≥50 copies/mL | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
| Normalized Neurocognitive Test Scores | -0.96 total neurocognitive z-score STANDARD_DEVIATION 0.79 | -0.97 total neurocognitive z-score STANDARD_DEVIATION 0.7 | -1.09 total neurocognitive z-score STANDARD_DEVIATION 0.7 | -1.00 total neurocognitive z-score STANDARD_DEVIATION 0.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 6 Participants | 6 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 30 Participants | 37 Participants | 97 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 23 Participants | 29 Participants | 16 Participants | 68 Participants |
| Sex: Female, Male Female | 15 Participants | 23 Participants | 18 Participants | 56 Participants |
| Sex: Female, Male Male | 48 Participants | 44 Participants | 43 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 63 | 0 / 67 | 0 / 60 |
| other Total, other adverse events | 31 / 63 | 32 / 67 | 37 / 60 |
| serious Total, serious adverse events | 6 / 63 | 12 / 67 | 9 / 60 |
Outcome results
Primary
Change in Normalized Composite Neurocognitive Test Score at Week 48 From Baseline
The normalized composite neurocognitive test score (total z-score) was defined as the average of the z-scores from the following tests: Domestic (US-based) and International Participants: * Grooved pegboard dominant * Grooved pegboard non-dominant * Hopkins Verbal Learning Test (HVLT-R) Learning trials * HVLT-R Delayed recall * HVLT-R Delayed recognition * Semantic verbal fluency Domestic only: * Stroop color naming * Stroop word reading * Stroop interference trial * Letter fluency * Trail Making A * Trail Making B * WAIS-III Symbol search * Digit Symbol International only: * Timed Gait * Finger Tapping Dominant * Finger Tapping Non-dominant * Color Trail 1 Z-scores were calculated using a demographically appropriate norming process. Higher z-scores correspond with better neurocognitive performance. Change was calculated as the total z-score at Week 48 minus the total z-score at Baseline.
Time frame: Measured at Baseline and Week 48
Population: All participants who started study treatment were included in the analysis. Analysis performed under intention to treat (ITT) principle, all eligible randomized participants were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Normalized Composite Neurocognitive Test Score at Week 48 From Baseline | 0.20 total neurocognitive z-score |
| Arm B: DTG and Placebo MVC | Change in Normalized Composite Neurocognitive Test Score at Week 48 From Baseline | 0.26 total neurocognitive z-score |
| Arm C: MVC and DTG | Change in Normalized Composite Neurocognitive Test Score at Week 48 From Baseline | 0.31 total neurocognitive z-score |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in normalized composite neurocognitive test scores at Week 48 from baselinep-value: 0.6t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in normalized composite neurocognitive test scores at Week 48 from baselinep-value: 0.33t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in normalized composite neurocognitive test scores at Week 48 from baselinep-value: 0.61t-test, 2 sided
Secondary
CD4+ T-cell Counts
CD4+ T-cell counts were recorded at the given time point
Time frame: Measured at Weeks 24, 48, and 96
Population: The analysis included all participants who started study treatment and had CD4+ T-cell counts measured at the scheduled study visits.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | CD4+ T-cell Counts | CD4 Count (Week 48) | 638 cells/mm^3 |
| Arm A: Placebo MVC and Placebo DTG | CD4+ T-cell Counts | CD4 Count (Week 24) | 660 cells/mm^3 |
| Arm A: Placebo MVC and Placebo DTG | CD4+ T-cell Counts | CD4 Count (Week 96) | 674 cells/mm^3 |
| Arm B: DTG and Placebo MVC | CD4+ T-cell Counts | CD4 Count (Week 48) | 691 cells/mm^3 |
| Arm B: DTG and Placebo MVC | CD4+ T-cell Counts | CD4 Count (Week 24) | 669 cells/mm^3 |
| Arm B: DTG and Placebo MVC | CD4+ T-cell Counts | CD4 Count (Week 96) | 720 cells/mm^3 |
| Arm C: MVC and DTG | CD4+ T-cell Counts | CD4 Count (Week 24) | 773 cells/mm^3 |
| Arm C: MVC and DTG | CD4+ T-cell Counts | CD4 Count (Week 96) | 788 cells/mm^3 |
| Arm C: MVC and DTG | CD4+ T-cell Counts | CD4 Count (Week 48) | 758 cells/mm^3 |
Secondary
CD8+ T-cell Counts
CD8+ T-cell counts were recorded at the given time point
Time frame: Measured at Weeks 24, 48, and 96
Population: The analysis included all participants who started study treatment and had CD8+ T-cell counts measured at the scheduled study visits.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | CD8+ T-cell Counts | CD8 Count (Week 48) | 742 cells/mm^3 |
| Arm A: Placebo MVC and Placebo DTG | CD8+ T-cell Counts | CD8 Count (Week 24) | 757 cells/mm^3 |
| Arm A: Placebo MVC and Placebo DTG | CD8+ T-cell Counts | CD8 Count (Week 96) | 747 cells/mm^3 |
| Arm B: DTG and Placebo MVC | CD8+ T-cell Counts | CD8 Count (Week 48) | 731 cells/mm^3 |
| Arm B: DTG and Placebo MVC | CD8+ T-cell Counts | CD8 Count (Week 24) | 752 cells/mm^3 |
| Arm B: DTG and Placebo MVC | CD8+ T-cell Counts | CD8 Count (Week 96) | 773 cells/mm^3 |
| Arm C: MVC and DTG | CD8+ T-cell Counts | CD8 Count (Week 24) | 862 cells/mm^3 |
| Arm C: MVC and DTG | CD8+ T-cell Counts | CD8 Count (Week 96) | 879 cells/mm^3 |
| Arm C: MVC and DTG | CD8+ T-cell Counts | CD8 Count (Week 48) | 856 cells/mm^3 |
Secondary
Change in CD4+ T-cell Count
Changes in CD4+ T-cell count were calculated as the CD4+ T-cell count at a given time point minus the CD4+ T-cell count at Baseline.
Time frame: Measured at Baseline and Weeks 24, 48, and 96
Population: The analysis included all participants who started study treatment and had CD4+ T-cell counts measured at the scheduled study visits.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 48) | -43 cells/mm^3 |
| Arm A: Placebo MVC and Placebo DTG | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 24) | -13 cells/mm^3 |
| Arm A: Placebo MVC and Placebo DTG | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 96) | -10 cells/mm^3 |
| Arm B: DTG and Placebo MVC | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 48) | -19 cells/mm^3 |
| Arm B: DTG and Placebo MVC | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 24) | -33 cells/mm^3 |
| Arm B: DTG and Placebo MVC | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 96) | 10 cells/mm^3 |
| Arm C: MVC and DTG | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 24) | 42 cells/mm^3 |
| Arm C: MVC and DTG | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 96) | 44 cells/mm^3 |
| Arm C: MVC and DTG | Change in CD4+ T-cell Count | Change from Baseline in CD4 Count (Week 48) | 21 cells/mm^3 |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in CD4+ T-cell count at Week 24 from baselinep-value: 0.67Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in CD4+ T-cell count at Week 48 from baselinep-value: 0.78Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in CD4+ T-cell count at Week 96 from baselinep-value: 0.94Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in CD4+ T-cell count at Week 24 from baselinep-value: 0.42Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in CD4+ T-cell count at Week 48 from baselinep-value: 0.07Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in CD4+ T-cell count at Week 96 from baselinep-value: 0.37Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in CD4+ T-cell count at Week 24 from baselinep-value: 0.08Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in CD4+ T-cell count at Week 48 from baselinep-value: 0.33Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in CD4+ T-cell count at Week 96 from baselinep-value: 0.56Wilcoxon (Mann-Whitney)
Secondary
Change in CD8+ T-cell Count
Changes in CD8+ T-cell count were calculated as the CD8+ T-cell count at a given time point minus the CD8+ T-cell count at baseline.
Time frame: Measured at Baseline and Weeks 24, 48, and 96
Population: The analysis included all participants who started study treatment and had CD8+ T-cell counts measured at the scheduled study visits.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 96) | -43 cells/mm^3 |
| Arm A: Placebo MVC and Placebo DTG | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 48) | -45 cells/mm^3 |
| Arm A: Placebo MVC and Placebo DTG | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 24) | -29 cells/mm^3 |
| Arm B: DTG and Placebo MVC | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 48) | -82 cells/mm^3 |
| Arm B: DTG and Placebo MVC | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 24) | -61 cells/mm^3 |
| Arm B: DTG and Placebo MVC | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 96) | -33 cells/mm^3 |
| Arm C: MVC and DTG | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 24) | 44 cells/mm^3 |
| Arm C: MVC and DTG | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 96) | 44 cells/mm^3 |
| Arm C: MVC and DTG | Change in CD8+ T-cell Count | Change from Baseline in CD8 Count (Week 48) | 35 cells/mm^3 |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in CD8+ T-cell count at Week 24 from baselinep-value: 0.63Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in CD8+ T-cell count at Week 48 from baselinep-value: 0.38Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in CD8+ T-cell count at Week 96 from baselinep-value: 0.95Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in CD8+ T-cell count at Week 24 from baselinep-value: 0.27Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in CD8+ T-cell count at Week 48 from baselinep-value: 0.23Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in CD8+ T-cell count at Week 96 from baselinep-value: 0.09Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in CD8+ T-cell count at Week 24 from baselinep-value: 0.03Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in CD8+ T-cell count at Week 48 from baselinep-value: 0.02Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in CD8+ T-cell count at Week 96 from baselinep-value: 0.09Wilcoxon (Mann-Whitney)
Secondary
Change in Functional Status Scores
Functional status scores were calculated based on the instrumental activities of daily living (IADLs) forms. IADL scores were calculated as the sum of the eight IADL tasks where the task scores were equal to 1 if a participant did not need assistance with the task and equal to 0 if a participant needed some level of help with the task. The maximum possible functional status score was 8, while the minimum possible functional status score was 0, with higher functional status scores indicating a higher level of functionality.
Time frame: Measured at Baseline and Weeks 24, 48, 72, and 96
Population: All participants who started study treatment were included in the analysis. Analysis performed under intention to treat (ITT) principle, all eligible randomized participants were included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 24) | 0.29 units on a scale |
| Arm A: Placebo MVC and Placebo DTG | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 48) | 0.38 units on a scale |
| Arm A: Placebo MVC and Placebo DTG | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 72) | 0.40 units on a scale |
| Arm A: Placebo MVC and Placebo DTG | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 96) | 0.16 units on a scale |
| Arm B: DTG and Placebo MVC | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 96) | 0.28 units on a scale |
| Arm B: DTG and Placebo MVC | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 24) | 0.43 units on a scale |
| Arm B: DTG and Placebo MVC | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 72) | 0.30 units on a scale |
| Arm B: DTG and Placebo MVC | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 48) | 0.45 units on a scale |
| Arm C: MVC and DTG | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 96) | 0.20 units on a scale |
| Arm C: MVC and DTG | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 48) | 0.10 units on a scale |
| Arm C: MVC and DTG | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 72) | 0.13 units on a scale |
| Arm C: MVC and DTG | Change in Functional Status Scores | Change from Baseline in IADL Score (Week 24) | 0.15 units on a scale |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in functional status scores at Week 24 from baselinep-value: 0.99Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in functional status scores at Week 48 from baselinep-value: 0.97Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in functional status scores at Week 72 from baselinep-value: 0.79Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in functional status scores at Week 96 from baselinep-value: 0.99Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in functional status scores at Week 24 from baselinep-value: 0.74Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in functional status scores at Week 48 from baselinep-value: 0.69Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in functional status scores at Week 72 from baselinep-value: 0.44Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in functional status scores at Week 96 from baselinep-value: 1Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in functional status scores at Week 24 from baselinep-value: 0.83Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in functional status scores at Week 48 from baselinep-value: 0.8Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in functional status scores at Week 72 from baselinep-value: 0.86Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in functional status scores at Week 96 from baselinep-value: 1Wilcoxon (Mann-Whitney)
Secondary
Change in Log10 IP-10 in CSF at Week 48 From Baseline
Changes in Log10 IP-10 in CSF were calculated as the Log10 IP-10 in CSF at Week 48 minus the Log10 IP-10 in CSF at Baseline.
Time frame: Measured at Baseline and Week 48
Population: The analysis population consisted of all participants who had CSF samples available at Baseline and Week 48
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Log10 IP-10 in CSF at Week 48 From Baseline | 0.02 Log10 pg/mL |
| Arm B: DTG and Placebo MVC | Change in Log10 IP-10 in CSF at Week 48 From Baseline | -0.11 Log10 pg/mL |
| Arm C: MVC and DTG | Change in Log10 IP-10 in CSF at Week 48 From Baseline | -0.36 Log10 pg/mL |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in Log10 IP-10 in CSF at Week 48 from baselinep-value: 0.59Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in Log10 IP-10 in CSF at Week 48 from baselinep-value: 0.39Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in Log10 IP-10 in CSF at Week 48 from baselinep-value: 0.8Wilcoxon (Mann-Whitney)
Secondary
Change in Log10 MIP-1 Beta in Cerebrospinal Fluid (CSF) at Week 48 From Baseline
Changes in Log10 MIP-1 Beta in CSF were calculated as the Log10 MIP-1 Beta in CSF at Week 48 minus the Log10 MIP-1 Beta in CSF at Baseline.
Time frame: Measured at Baseline and Week 48
Population: The analysis population consisted of all participants who had CSF samples available at Baseline and Week 48
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Log10 MIP-1 Beta in Cerebrospinal Fluid (CSF) at Week 48 From Baseline | -0.24 Log10 pg/mL |
| Arm B: DTG and Placebo MVC | Change in Log10 MIP-1 Beta in Cerebrospinal Fluid (CSF) at Week 48 From Baseline | -0.32 Log10 pg/mL |
| Arm C: MVC and DTG | Change in Log10 MIP-1 Beta in Cerebrospinal Fluid (CSF) at Week 48 From Baseline | 0.17 Log10 pg/mL |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in Log10 MIP-1 Beta in CSF at Week 48 from baselinep-value: 0.99Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in Log10 MIP-1 Beta in CSF at Week 48 from baselinep-value: 0.26Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in Log10 MIP-1 Beta in CSF at Week 48 from baselinep-value: 0.2Wilcoxon (Mann-Whitney)
Secondary
Change in Log10 MIP-1 Beta in Plasma at Week 48 From Baseline
Changes in Log10 MIP-1 Beta in Plasma were calculated as the Log10 MIP-1 Beta in Plasma at Week 48 minus the Log10 MIP-1 Beta in Plasma at Baseline. Results below the lower limit of quantification were set to the lower limit value of 11.
Time frame: Measured at Baseline and Week 48
Population: The analysis population consisted of all participants who had plasma samples available at Baseline and Week 48
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Log10 MIP-1 Beta in Plasma at Week 48 From Baseline | 0.05 Log10 pg/mL |
| Arm B: DTG and Placebo MVC | Change in Log10 MIP-1 Beta in Plasma at Week 48 From Baseline | -0.02 Log10 pg/mL |
| Arm C: MVC and DTG | Change in Log10 MIP-1 Beta in Plasma at Week 48 From Baseline | 0.30 Log10 pg/mL |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in Log10 MIP-1 Beta in plasma at Week 48 from baselinep-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in Log10 MIP-1 Beta in plasma at Week 48 from baselinep-value: <0.01Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in Log10 MIP-1 Beta in plasma at Week 48 from baselinep-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Change in Log10 Neopterin in CSF at Week 48 From Baseline
Changes in Log10 Neopterin in CSF were calculated as the Log10 Neopterin in CSF at Week 48 minus the Log10 Neopterin in CSF at Baseline.
Time frame: Measured at Baseline and Week 48
Population: The analysis population consisted of all participants who had CSF samples available at Baseline and Week 48
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Log10 Neopterin in CSF at Week 48 From Baseline | 0.01 Log10 nmol/L |
| Arm B: DTG and Placebo MVC | Change in Log10 Neopterin in CSF at Week 48 From Baseline | -0.06 Log10 nmol/L |
| Arm C: MVC and DTG | Change in Log10 Neopterin in CSF at Week 48 From Baseline | -0.17 Log10 nmol/L |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in Log10 Neopterin in CSF at Week 48 from baselinep-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in Log10 Neopterin in CSF at Week 48 from baselinep-value: 0.14Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in Log10 Neopterin in CSF at Week 48 from baselinep-value: 0.49Wilcoxon (Mann-Whitney)
Secondary
Change in Log10 NFL in CSF at Week 48 From Baseline
Changes in Log10 NFL in CSF were calculated as the Log10 NFL in CSF at Week 48 minus the Log10 NFL in CSF at Baseline.
Time frame: Measured at Baseline and Week 48
Population: The analysis population consisted of all participants who had CSF samples available at Baseline and Week 48
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Log10 NFL in CSF at Week 48 From Baseline | -0.02 Log10 pg/mL |
| Arm B: DTG and Placebo MVC | Change in Log10 NFL in CSF at Week 48 From Baseline | -0.05 Log10 pg/mL |
| Arm C: MVC and DTG | Change in Log10 NFL in CSF at Week 48 From Baseline | 0.00 Log10 pg/mL |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in Log10 NFL in CSF at Week 48 from baselinep-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in Log10 NFL in CSF at Week 48 from baselinep-value: 0.99Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in Log10 NFL in CSF at Week 48 from baselinep-value: 0.54Wilcoxon (Mann-Whitney)
Secondary
Change in Log10 sCD14 in Plasma at Week 48 From Baseline
Changes in Log10 sCD14 in Plasma were calculated as the Log10 sCD14 in Plasma at Week 48 minus the Log10 sCD14 in Plasma at Baseline.
Time frame: Measured at Baseline and Week 48
Population: The analysis population consisted of all participants who had plasma samples available at Baseline and Week 48.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Log10 sCD14 in Plasma at Week 48 From Baseline | 0.04 Log10 ng/mL |
| Arm B: DTG and Placebo MVC | Change in Log10 sCD14 in Plasma at Week 48 From Baseline | 0.03 Log10 ng/mL |
| Arm C: MVC and DTG | Change in Log10 sCD14 in Plasma at Week 48 From Baseline | 0.01 Log10 ng/mL |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in Log10 sCD14 in plasma at Week 48 from baselinep-value: 1Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in Log10 sCD14 in plasma at Week 48 from baselinep-value: 0.95Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in Log10 sCD14 in plasma at Week 48 from baselinep-value: 0.96Wilcoxon (Mann-Whitney)
Secondary
Change in Log10 sTNFr-II in Plasma at Week 48 From Baseline
Changes in Log10 sTNFr-II in Plasma were calculated as the Log10 sTNFr-II in Plasma at Week 48 minus the Log10 sTNFr-II in Plasma at Baseline.
Time frame: Measured at Baseline and Week 48
Population: The analysis population consisted of all participants who had plasma samples available at Baseline and Week 48
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Log10 sTNFr-II in Plasma at Week 48 From Baseline | 0.02 Log10 pg/mL |
| Arm B: DTG and Placebo MVC | Change in Log10 sTNFr-II in Plasma at Week 48 From Baseline | 0.01 Log10 pg/mL |
| Arm C: MVC and DTG | Change in Log10 sTNFr-II in Plasma at Week 48 From Baseline | 0.00 Log10 pg/mL |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in Log10 sTNFr-II in plasma at Week 48 from baselinep-value: 0.91Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in Log10 sTNFr-II in plasma at Week 48 from baselinep-value: 0.86Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in Log10 sTNFr-II in plasma at Week 48 from baselinep-value: 0.94Wilcoxon (Mann-Whitney)
Secondary
Change in Log10 VCAM in Plasma at Week 48 From Baseline
Changes in Log10 VCAM in Plasma were calculated as the Log10 VCAM in Plasma at Week 48 minus the Log10 VCAM in Plasma at Baseline.
Time frame: Measured at Baseline and Week 48
Population: The analysis population consisted of all participants who had plasma samples available at Baseline and Week 48
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Log10 VCAM in Plasma at Week 48 From Baseline | 0.01 Log10 pg/mL |
| Arm B: DTG and Placebo MVC | Change in Log10 VCAM in Plasma at Week 48 From Baseline | 0.00 Log10 pg/mL |
| Arm C: MVC and DTG | Change in Log10 VCAM in Plasma at Week 48 From Baseline | 0.00 Log10 pg/mL |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in Log10 VCAM in plasma at Week 48 from baselinep-value: 0.7Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in Log10 VCAM in plasma at Week 48 from baselinep-value: 0.28Wilcoxon (Mann-Whitney)
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in Log10 VCAM in plasma at Week 48 from baselinep-value: 0.85Wilcoxon (Mann-Whitney)
Secondary
Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline
The normalized composite neurocognitive test score (total z-score) was defined as the average of the z-scores from the following tests: Domestic and International Participants: * Grooved pegboard dominant * Grooved pegboard non-dominant * HVLT-R Learning trials * HVLT-R Delayed recall * HVLT-R Delayed recognition * Semantic verbal fluency Domestic only: * Stroop color naming * Stroop word reading * Stroop interference trial * Letter fluency * Trail Making A * Trail Making B * WAIS-III Symbol search * Digit Symbol International only: * Timed Gait * Finger Tapping Dominant * Finger Tapping Non-dominant * Color Trail 1 * Color Trail 2 Z-scores were calculated using a demographically appropriate norming process. Higher z-scores correspond with better neurocognitive performance. Change was calculated as the total z-score at the given time point minus the total z-score at Baseline.
Time frame: Measured at Baseline and Weeks 24, 72, and 96
Population: All participants who started study treatment were included in the analysis. Analysis performed under intention to treat (ITT) principle, all eligible randomized participants were included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 72) | 0.29 total neurocognitive z-score |
| Arm A: Placebo MVC and Placebo DTG | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 24) | 0.14 total neurocognitive z-score |
| Arm A: Placebo MVC and Placebo DTG | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 96) | 0.37 total neurocognitive z-score |
| Arm B: DTG and Placebo MVC | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 72) | 0.32 total neurocognitive z-score |
| Arm B: DTG and Placebo MVC | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 24) | 0.18 total neurocognitive z-score |
| Arm B: DTG and Placebo MVC | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 96) | 0.34 total neurocognitive z-score |
| Arm C: MVC and DTG | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 24) | 0.20 total neurocognitive z-score |
| Arm C: MVC and DTG | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 96) | 0.38 total neurocognitive z-score |
| Arm C: MVC and DTG | Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline | Change of Normalized Composite Neurocognitive Test Score (Week 72) | 0.37 total neurocognitive z-score |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in normalized composite neurocognitive test scores at Week 24 from baselinep-value: 0.61t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in normalized composite neurocognitive test scores at Week 72 from baselinep-value: 0.72t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in change in normalized composite neurocognitive test scores at Week 96 from baselinep-value: 0.79t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in normalized composite neurocognitive test scores at Week 24 from baselinep-value: 0.55t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in normalized composite neurocognitive test scores at Week 72 from baselinep-value: 0.47t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in change in normalized composite neurocognitive test scores at Week 96 from baselinep-value: 0.95t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in normalized composite neurocognitive test scores at Week 24 from baselinep-value: 0.85t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in normalized composite neurocognitive test scores at Week 72 from baselinep-value: 0.67t-test, 2 sided
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in change in normalized composite neurocognitive test scores at Week 96 from baselinep-value: 0.7t-test, 2 sided
Secondary
Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL
The number of participants with Plasma HIV-1 RNA greater than or equal to 50 copies/mL was assessed at each given time point.
Time frame: Measured at Weeks 24, 48, and 96
Population: The analysis included all participants who started study treatment and had Plasma HIV-1 RNA measured at the scheduled study visits.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 48) | 3 Participants |
| Arm A: Placebo MVC and Placebo DTG | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 24) | 3 Participants |
| Arm A: Placebo MVC and Placebo DTG | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 96) | 1 Participants |
| Arm B: DTG and Placebo MVC | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 48) | 0 Participants |
| Arm B: DTG and Placebo MVC | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 24) | 1 Participants |
| Arm B: DTG and Placebo MVC | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 96) | 6 Participants |
| Arm C: MVC and DTG | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 24) | 1 Participants |
| Arm C: MVC and DTG | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 96) | 2 Participants |
| Arm C: MVC and DTG | Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL | HIV RNA (Week 48) | 1 Participants |
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 2495% CI: [-2.78, 9.42]
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 4895% CI: [-0.53, 10.87]
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm B: DTG and placebo MVC in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 9695% CI: [-16.56, 0.13]
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 2495% CI: [-3.07, 9.42]
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 4895% CI: [-3.11, 10.06]
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm A: Placebo MVC and placebo DTG and Arm C: MVC and DTG in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 9695% CI: [-7.89, 4.19]
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 2495% CI: [-4.53, 4.23]
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 4895% CI: [-4.99, 1.6]
Comparison: Under the null hypothesis, it was assumed there was no difference between Arm B: DTG and placebo MVC and Arm C: MVC and DTG in number of participants with HIV-1 RNA ≥ 50 copies/mL at Week 9695% CI: [-2.7, 15.42]
Secondary
Number of Participants With Treatment Related Adverse Events (AEs)
Treatment Related Adverse Events were determined by the study sites indicating a relationship between an adverse event and the study treatment.
Time frame: Measured from treatment initiation through Week 96
Population: All participants who were randomized were included in the analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Placebo MVC and Placebo DTG | Number of Participants With Treatment Related Adverse Events (AEs) | 3 Participants |
| Arm B: DTG and Placebo MVC | Number of Participants With Treatment Related Adverse Events (AEs) | 5 Participants |
| Arm C: MVC and DTG | Number of Participants With Treatment Related Adverse Events (AEs) | 7 Participants |
Other Pre-specified
Changes in Cell-associated HIV-1 RNA/DNA/2-long Terminal Repeat Sequences (LTR) Circles and Single Copy Assay (SCA)
This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome due to lack of funding for testing.
Time frame: Measured at Baseline and Week 48
Other Pre-specified
Changes in Residual Viremia
This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome due to lack of funding for testing.
Time frame: Measured at Baseline and Week 48
Other Pre-specified
Changes in T Cell and Monocyte Activation
This outcome measure was listed as secondary in the protocol but the intention was as an exploratory outcome due to lack of funding for testing.
Time frame: Measured at Baseline and Week 48