HIV-1 Infection
Conditions
Brief summary
The main purpose of this study was to compare the effects on bones of the following two drug combinations: * maraviroc (MVC), emtricitabine (FTC), plus darunavir/ritonavir (DRV/r) * tenofovir (TDF) plus emtricitabine (FTC) plus darunavir/ritonavir (DRV/r) Additional study objectives were the following: * To see how the drug combinations affect the brain and kidneys. * To see how well the drug combinations lower the HIV viral load. * To see how safe the drug combinations are, how well people are able to take the study drug combinations, and how well their immune systems respond to the study drugs.
Detailed description
There are now several HIV treatment options for a person with HIV infection who has not yet been treated. Most people who receive treatment and take their medications as directed have a good result. This is usually determined by measuring the amount of HIV in the blood (viral load). The best response is when HIV cannot be found (less than 50 copies/mL) in the blood. However, it has recently become clear that some people with HIV who are receiving effective HIV drugs continue to have more health problems than people without HIV infection. Sometimes, there is damage to organs in the body, including bone, kidneys, and the brain.
Interventions
Placebo for maraviroc was administered orally once a day as one tablet.
DRUGTenofovir disoproxil fumarate
Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.
DRUGEmtricitabine
Emtricitabine was administered orally once a day as one 200 mg capsule.
DRUGPlacebo for Tenofovir disoproxil fumarate
Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.
DRUGDarunavir
Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.
DRUGRitonavir
Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.
DRUGMaraviroc
Maraviroc was administered orally once a day as one 150 mg tablet.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
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
* HIV-1 infection * No evidence of exclusionary resistance mutations defined as evidence of any major NRTI mutation according to the current IAS list of HIV-1 Resistance Mutations Associated with Drug Resistance, or any DRV RAMs (refer to the A5303 PSWP for a list of these mutations) on any genotype; or evidence of significant NRTI or DRV resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations were not exclusionary. * ARV drug-naïve, defined as \</=10 days of ART at any time prior to study entry, except in the instances defined in section 4.1.3 of the protocol. * R5-only tropism based on Trofile testing performed within 90 days prior to study entry. * Screening HIV-1 RNA \>1000 copies/mL obtained within 90 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification or its equivalent. * Known hepatitis C virus (HCV) antibody status (performed at any laboratory that had a CLIA certification or its equivalent). * Certain laboratory values obtained within 60 days prior to study entry, as defined in section 4.1.7 of the protocol. * For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of ≤25 mIU/mL within 72 hours prior to study entry. * Female subjects of reproductive potential, who were participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception (as defined in section 4.1.9.1 of the protocol) while receiving the study drugs and for 6 weeks after stopping the medications. * Female subjects who were not of reproductive potential or whose male partner(s) had azoospermia were eligible to take study drugs without the use of contraceptives. * Ability and willingness of subject or legal guardian/representative to give written informed consent. * Willingness to undergo neuropsychological testing. * DXA scan performed after confirmation of the subject's eligibility by Trofile testing but no more than 4 weeks prior to randomization.
Exclusion criteria
* Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. * New use of hormonal therapies within 6 months prior to study entry. (Stable therapy for ≥6 months was permitted.) * New use of oral contraceptive pills (OCPs) in the past 3 months. (Stable therapy for ≥3 months was permitted.) * Any oral, intravenous, or inhaled steroids within 30 days prior to study entry. (Intranasal steroids and topical corticosteroids were allowed.) * Known allergy/sensitivity to study drugs or their formulations. (A history of sulfa allergy was not an exclusionary condition.) * Known hypersensitivity to soy lecithin. * Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or was clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry. (Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) were not exclusionary conditions.) * Requirement for any current medications that were prohibited with any study drugs. (Prohibited medications must be discontinued at least 30 days prior to entry. Refer to the A5303 PSWP for a list of prohibited medications.) * The presence of decompensated cirrhosis. * A history of or current, active HBV infection defined as positive hepatitis B surface antigen test (or positive HBV DNA in subjects with isolated HBcAb positivity, defined as negative HBsAg, negative HBsAb, and positive HBcAb) at screening. * Current or prior use of biphosphonates, teriparatide, raloxifene, or denosumab. * Weight \>300 lbs (exceeds weight limit of DXA scanners). * History after 18 years of age of fracture of the spine, hip, wrist, or other site thought to be related to osteoporosis or bone fragility. * Currently breastfeeding. * Any active psychiatric illness including schizophrenia, severe depression, or severe bipolar affective disorder that, in the opinion of the investigator, could confound the analysis of the neurological examination or neuropsychological test results. * Active drug or alcohol abuse that, in the investigator's opinion, could prevent compliance with study procedures or confound the analysis of study endpoints. * Active brain infection (except for HIV-1), fungal meningitis, toxoplasmosis, central nervous system (CNS) lymphoma, brain neoplasm, or space-occupying brain lesion requiring acute or chronic therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) | Week 0, week 48 | The primary endpoint is the percent change in bone mineral density (BMD) at total hip (as measured by DXA scan) from baseline (week 0) to week 48. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CD4 Count From Baseline to Week 24 | Week 0, week 24 | Change in CD4 count from baseline (week 0) to week 24 |
| Change in CD4 Count From Baseline to Week 48 | Week 0, week 48 | Change in CD4 count from baseline (week 0) to week 48 |
| CD8+ T-cell Change From Baseline to Week 48 | At weeks 0 and 48 | CD8+ T-cell change from baseline to week 48 |
| Percentage Change in Expression of CD38+/HLA-DR+ on CD4+ T Cells From Baseline to Week 48 | At weeks 0 and 48 | percentage change is define as \[ (week 48 - week 0) / week 0 \] \* 100% |
| Percentage Change in Expression of CD38+/HLA-DR+ on CD8+ T Cells From Baseline to Week 48 | At weeks 0 and 48 | percentage change is defined as \[ (week 48 - week 0) / week 0 \] \* 100% |
| Percent Change in Expression of CD28+/CD57+ on CD8+ T Cells From Baseline to Week 48 | At weeks 0 and 48 | percentage change is define as \[ (week 48 - week 0) / week 0 \] \* 100% |
| Percent Change in Expression of CD57+ on CD8+ T Cells From Baseline to Week 48 | At weeks 0 and 48 | percentage change is define as \[ (week 48 - week 0) / week 0 \] \* 100% |
| Percent Change in Expression of CD28+ on CD8+ T Cells From Baseline to Week 48 | At weeks 0 and 48 | percentage change is define as \[ (week 48 - week 0) / week 0 \] \* 100% |
| Percent Change in Expression of RANKL+ on CD8+ T Cells From Baseline to Week 48 | At weeks 0 and 48 | percentage change is defined as \[ (week 48 - week 0) / week 0 \] \* 100% |
| Percent Change in Lumbar Spine Bone Mineral Density (BMD) | Week 0, week 48 | The percent change in bone mineral density (BMD) at lumbar spine (as measured by DXA scan) from baseline (week 0) to week 48. |
| Change in Level of IP-10 From Baseline to Week 48 | At weeks 0 and 48 | Change in level of Interferon gamma-induced protein 10 (IP-10) from baseline to week 48 |
| Change in Levels of sCD163 From Baseline to Week 48 | At weeks 0 and 48 | Change in levels of soluble CD163 from baseline to week 48 |
| Change in Levels of sCD14 From Baseline | At weeks 0 and 48 | Change in levels of soluble CD14 from baseline |
| Change in Levels of D-dimer From Baseline | At weeks 0 and 48 | Change in levels of D-dimer from baseline |
| Cumulative Probability of Virologic Failure by Week 48 | From study treatment initiation to week 48 | Confirmed virologic failure is defined as confirmed plasma HIV-1 RNA levels \> 1000 copies/mL at or after week 16 and before week 24, or confirmed HIV-1 RNA levels\> 200 copies/mL at or after week 24. Participants who discontinued the study with an unconfirmed virologic failure (HIV-1 RNA \> 1000 copies at 16 weeks or HIV-1 RNA level \> 200 copies/mL at or after week 24) are considered as virologic failures at the study visit week of the unconfirmed value. Time to virologic failure is defined as the time from study entry to the planned visit week of the initial failure. Product-limit estimates for the survival function were used to estimate the cumulative probability of virologic failure over time and its corresponding 95% confidence interval for each treatment group. |
| Number of Participants Who Experienced Bone Fractures | From study treatment initiation to week 48 | Number of participants who experienced bone fractures during the study |
| Number of Participants Who Died During the Study | From study treatment initiation to week 48 | Number of participants who died during the study |
| Number of Participants Who Developed Grade 3 or 4 Primary Adverse Events | From study treatment initiation to week 48 | Grade 3 or 4 primary adverse events includes primary signs/symptoms, primary laboratory abnormalities, or primary diagnoses. See DAIDS AE Grading Table Version 1.0, Dec 2004 (Clarification, Aug 2009) |
| Change in Levels of IL-6 From Baseline to Week 48 | At weeks 0 and 48 | Change in levels of Interleukin 6 (IL-6) from baseline to week 48 |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
A5303 opened under version 1.0 on 12/4/11, and the first participant was enrolled on 1/17/12. Accrual to the study closed on 6/12/13, with a total of 262 participants enrolled at 38 sites
Participants by arm
| Arm | Count |
|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD
Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.
Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.
Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule.
Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet. | 130 |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD
Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.
Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.
Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.
Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule.
Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet. | 129 |
| Total | 259 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 7 |
| Overall Study | Never started study treatment | 0 | 3 |
| Overall Study | Unable to complete | 3 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Total | TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | MVC Arm (DRV/r + MVC + FTC + TDF Placebo) |
|---|---|---|---|
| Age, Continuous | 33 years | 33 years | 33 years |
| Age, Customized 18-29 Years | 97 participants | 48 participants | 49 participants |
| Age, Customized 30-39 Years | 81 participants | 41 participants | 40 participants |
| Age, Customized 40-49 Years | 50 participants | 24 participants | 26 participants |
| Age, Customized >=50 Years | 31 participants | 16 participants | 15 participants |
| CD4 count | 390 cells/mm^3 | 392 cells/mm^3 | 389 cells/mm^3 |
| HIV-1 RNA | 4.50 log10 copies/mL | 4.47 log10 copies/mL | 4.59 log10 copies/mL |
| Race/Ethnicity, Customized American Indian, Alaskan Native | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Asian, Pacific Islander | 3 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Black non-Hispanic | 78 participants | 33 participants | 45 participants |
| Race/Ethnicity, Customized Hispanic (regardless of race) | 58 participants | 34 participants | 24 participants |
| Race/Ethnicity, Customized More than one race | 3 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White non-Hispanic | 116 participants | 59 participants | 57 participants |
| Region of Enrollment Puerto Rico | 5 participants | 2 participants | 3 participants |
| Region of Enrollment United States | 254 participants | 127 participants | 127 participants |
| Sex: Female, Male Female | 24 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 235 Participants | 120 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 101 / 130 | 78 / 129 |
| serious Total, serious adverse events | 10 / 130 | 4 / 129 |
Outcome results
Primary
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD)
The primary endpoint is the percent change in bone mineral density (BMD) at total hip (as measured by DXA scan) from baseline (week 0) to week 48.
Time frame: Week 0, week 48
Population: The primary analysis was as-treated which included only participants with total hip BMD measurements available at both week 0 and week 48 who remained on their randomized MVC or TDF component by the time week 48 measurement was taken without an interruption of treatment of more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) | -1.51 percentage change |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) | -2.40 percentage change |
Comparison: The null hypothesis is that there is no difference between the two arms in the percent of total hip BMD change from baseline to week 48p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
CD8+ T-cell Change From Baseline to Week 48
CD8+ T-cell change from baseline to week 48
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | CD8+ T-cell Change From Baseline to Week 48 | -6 cell/mm^3 |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | CD8+ T-cell Change From Baseline to Week 48 | -109 cell/mm^3 |
Secondary
Change in CD4 Count From Baseline to Week 24
Change in CD4 count from baseline (week 0) to week 24
Time frame: Week 0, week 24
Population: Change in total CD4 count is analyzed in the same as-treated population as in the primary as-treated analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Change in CD4 Count From Baseline to Week 24 | 165 cells/mm^3 |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Change in CD4 Count From Baseline to Week 24 | 127 cells/mm^3 |
Secondary
Change in CD4 Count From Baseline to Week 48
Change in CD4 count from baseline (week 0) to week 48
Time frame: Week 0, week 48
Population: Change in total CD4 count is analyzed in the same as-treated population as in the primary as-treated analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Change in CD4 Count From Baseline to Week 48 | 234 cells/mm^3 |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Change in CD4 Count From Baseline to Week 48 | 188 cells/mm^3 |
Secondary
Change in Level of IP-10 From Baseline to Week 48
Change in level of Interferon gamma-induced protein 10 (IP-10) from baseline to week 48
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Change in Level of IP-10 From Baseline to Week 48 | -198 pg/ml |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Change in Level of IP-10 From Baseline to Week 48 | -170 pg/ml |
Secondary
Change in Levels of D-dimer From Baseline
Change in levels of D-dimer from baseline
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Change in Levels of D-dimer From Baseline | -82 ng/ml |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Change in Levels of D-dimer From Baseline | -61 ng/ml |
Secondary
Change in Levels of IL-6 From Baseline to Week 48
Change in levels of Interleukin 6 (IL-6) from baseline to week 48
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Change in Levels of IL-6 From Baseline to Week 48 | -0.21 pg/ml |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Change in Levels of IL-6 From Baseline to Week 48 | -0.12 pg/ml |
Secondary
Change in Levels of sCD14 From Baseline
Change in levels of soluble CD14 from baseline
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Change in Levels of sCD14 From Baseline | -103 ng/ml |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Change in Levels of sCD14 From Baseline | -10 ng/ml |
Secondary
Change in Levels of sCD163 From Baseline to Week 48
Change in levels of soluble CD163 from baseline to week 48
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Change in Levels of sCD163 From Baseline to Week 48 | -250 ng/ml |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Change in Levels of sCD163 From Baseline to Week 48 | -258 ng/ml |
Secondary
Cumulative Probability of Virologic Failure by Week 48
Confirmed virologic failure is defined as confirmed plasma HIV-1 RNA levels \> 1000 copies/mL at or after week 16 and before week 24, or confirmed HIV-1 RNA levels\> 200 copies/mL at or after week 24. Participants who discontinued the study with an unconfirmed virologic failure (HIV-1 RNA \> 1000 copies at 16 weeks or HIV-1 RNA level \> 200 copies/mL at or after week 24) are considered as virologic failures at the study visit week of the unconfirmed value. Time to virologic failure is defined as the time from study entry to the planned visit week of the initial failure. Product-limit estimates for the survival function were used to estimate the cumulative probability of virologic failure over time and its corresponding 95% confidence interval for each treatment group.
Time frame: From study treatment initiation to week 48
Population: All participants who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Cumulative Probability of Virologic Failure by Week 48 | 6 cumulative probability per 100 persons |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Cumulative Probability of Virologic Failure by Week 48 | 5 cumulative probability per 100 persons |
Secondary
Number of Participants Who Developed Grade 3 or 4 Primary Adverse Events
Grade 3 or 4 primary adverse events includes primary signs/symptoms, primary laboratory abnormalities, or primary diagnoses. See DAIDS AE Grading Table Version 1.0, Dec 2004 (Clarification, Aug 2009)
Time frame: From study treatment initiation to week 48
Population: All participants who initiated study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Number of Participants Who Developed Grade 3 or 4 Primary Adverse Events | 16 participants |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Number of Participants Who Developed Grade 3 or 4 Primary Adverse Events | 22 participants |
Secondary
Number of Participants Who Died During the Study
Number of participants who died during the study
Time frame: From study treatment initiation to week 48
Population: All participants who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Number of Participants Who Died During the Study | 0 participants |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Number of Participants Who Died During the Study | 0 participants |
Secondary
Number of Participants Who Experienced Bone Fractures
Number of participants who experienced bone fractures during the study
Time frame: From study treatment initiation to week 48
Population: All participants who started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Number of Participants Who Experienced Bone Fractures | 2 participants |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Number of Participants Who Experienced Bone Fractures | 2 participants |
Secondary
Percentage Change in Expression of CD38+/HLA-DR+ on CD4+ T Cells From Baseline to Week 48
percentage change is define as \[ (week 48 - week 0) / week 0 \] \* 100%
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Percentage Change in Expression of CD38+/HLA-DR+ on CD4+ T Cells From Baseline to Week 48 | -52.1 percentage change |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Percentage Change in Expression of CD38+/HLA-DR+ on CD4+ T Cells From Baseline to Week 48 | -48.6 percentage change |
Secondary
Percentage Change in Expression of CD38+/HLA-DR+ on CD8+ T Cells From Baseline to Week 48
percentage change is defined as \[ (week 48 - week 0) / week 0 \] \* 100%
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Percentage Change in Expression of CD38+/HLA-DR+ on CD8+ T Cells From Baseline to Week 48 | -59.5 percentage change |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Percentage Change in Expression of CD38+/HLA-DR+ on CD8+ T Cells From Baseline to Week 48 | -60.9 percentage change |
Secondary
Percent Change in Expression of CD28+/CD57+ on CD8+ T Cells From Baseline to Week 48
percentage change is define as \[ (week 48 - week 0) / week 0 \] \* 100%
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Percent Change in Expression of CD28+/CD57+ on CD8+ T Cells From Baseline to Week 48 | -9.1 percentage change |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Percent Change in Expression of CD28+/CD57+ on CD8+ T Cells From Baseline to Week 48 | -11.2 percentage change |
Secondary
Percent Change in Expression of CD28+ on CD8+ T Cells From Baseline to Week 48
percentage change is define as \[ (week 48 - week 0) / week 0 \] \* 100%
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Percent Change in Expression of CD28+ on CD8+ T Cells From Baseline to Week 48 | 11.9 percentage change |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Percent Change in Expression of CD28+ on CD8+ T Cells From Baseline to Week 48 | 14.0 percentage change |
Secondary
Percent Change in Expression of CD57+ on CD8+ T Cells From Baseline to Week 48
percentage change is define as \[ (week 48 - week 0) / week 0 \] \* 100%
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Percent Change in Expression of CD57+ on CD8+ T Cells From Baseline to Week 48 | -3.5 percentage change |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Percent Change in Expression of CD57+ on CD8+ T Cells From Baseline to Week 48 | -4.6 percentage change |
Secondary
Percent Change in Expression of RANKL+ on CD8+ T Cells From Baseline to Week 48
percentage change is defined as \[ (week 48 - week 0) / week 0 \] \* 100%
Time frame: At weeks 0 and 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Percent Change in Expression of RANKL+ on CD8+ T Cells From Baseline to Week 48 | -20.7 percentage change |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Percent Change in Expression of RANKL+ on CD8+ T Cells From Baseline to Week 48 | -17.0 percentage change |
Secondary
Percent Change in Lumbar Spine Bone Mineral Density (BMD)
The percent change in bone mineral density (BMD) at lumbar spine (as measured by DXA scan) from baseline (week 0) to week 48.
Time frame: Week 0, week 48
Population: As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVC Arm (DRV/r + MVC + FTC + TDF Placebo) | Percent Change in Lumbar Spine Bone Mineral Density (BMD) | -0.88 percentage change |
| TDF Arm (DRV/r + TDF + FTC + MVC Placebo) | Percent Change in Lumbar Spine Bone Mineral Density (BMD) | -2.35 percentage change |