HIV-1 Infection
Conditions
Brief summary
HIV-infected people can have an increase in inflammation in their body organs, even after taking anti-HIV medicines. Sevelamer carbonate is used to bind phosphate in dialysis patients. It can also bind endotoxin in the gut and lowers endotoxin levels in the blood of dialysis patients. Sevelamer carbonate decreases the inflammation endotoxin causes in dialysis patients. A5296 is a phase II, single-arm study to evaluate the effect of 8 weeks of sevelamer carbonate administration on markers of microbial translocation and T-cell activation in the blood in chronically HIV-infected subjects not receiving ART.
Detailed description
HIV-infected people can have an increase in inflammation in their body organs, even after taking anti-HIV medicines. Inflammation is a normal body reaction to any infection. However, if inflammation lasts a long time like in HIV infection, it may lead to complications, such as heart disease, cancer, liver disease, and problems with thinking. Also, HIV-infected people with high inflammation have lower CD4+ T-cell counts (cells that fight infection). Many HIV researchers are studying the harmful effects of this prolonged inflammation and possible ways to prevent these complications. The increase in inflammation in HIV-infected people may be caused by HIV or by other factors such as parts of bacteria. These bacterial pieces, called endotoxins, do not cause harm in the intestine (gut). However, in HIV infection, there is damage to the gut that allows endotoxins to cross from the gut into the blood. These endotoxins then cause inflammation in the body. New research is focusing on strategies to reduce the levels of endotoxin as a way to decrease inflammation. A drug called sevelamer carbonate is used to bind phosphate in dialysis patients. However, sevelamer carbonate also binds endotoxin in the gut and lowers endotoxin levels in the blood of dialysis patients. Sevelamer carbonate also decreases the inflammation endotoxin causes in dialysis patients. This study will see if sevelamer carbonate can have the same effects in HIV-infected patients. A5296 is a phase II, single-arm study to evaluate the effect of 8 weeks of sevelamer carbonate administration on markers of microbial translocation as well as monocyte and T-cell activation in the blood in chronically HIV-infected subjects with CD4+ T-cell count ≥ 400 cells/mm3 not receiving ART. This study enrolled 40 subjects. To assess whether there is a persistent effect of study drug, subjects were observed for an additional 8 weeks off sevelamer carbonate and changes in biomarkers were monitored. As A5296 is a phase II study of biologic activity, the primary and secondary analyses are as-treated, limited to subjects who have data for baseline and week 8 and who remain on study treatment through week 8. For any subject who initiated antiretroviral treatment (ART), analyses only included data collected prior to the time ART was started.
Interventions
DRUGSevelamer carbonate
Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection * No plans to initiate ART during the course of the proposed study. * Screening CD4+ T-cell count ≥ 400 cells/mm3 performed in a laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent. * HIV-1 RNA \>50 copies/mL within the last 180 days prior to entry. * Screening serum phosphate \> 2.6 mg/dL within 60 days prior to entry. * Certain laboratory values, as detailed in section 4.1.6 of the protocol, obtained within 30 days prior to entry * Female subjects of reproductive potential must have a negative serum or urine pregnancy test performed within 30 days prior to entry. * Female subjects participating in sexual activity that could lead to pregnancy must agree to use at least one of the following forms of birth control for at least 30 days prior to study entry until the final study visit: * Condoms (male or female) with or without a spermicidal agent * Diaphragm or cervical cap with spermicide * Intrauterine device (IUD) * Hormone-based contraceptive * Female subjects who are not of reproductive potential are eligible without requiring the use of a contraceptive. * Confirmation of the availability of the stored pre-entry plasma and peripheral blood mononuclear cell (PBMC) samples for endotoxin, sCD14, and immune activation determinations, obtained from a fasting sample. * Ability and willingness of subject to provide informed consent. * No plans to use probiotics (defined as products that contain significant amounts of live microorganisms and are ingested for specific health benefits, e.g., yogurt with live and active cultures, Lactobacillus GG, Saccharomyces boulardii) during the study.
Exclusion criteria
* Known diagnosis of acute HIV infection within 180 days prior to study entry. * Pregnant or breastfeeding. * Use of any antiretroviral agent within 24 weeks prior to study entry. * Use of systemic cancer chemotherapy or radiation therapy, immunosuppressive or immunomodulatory therapy (e.g., interferons, tumor necrosis factor antagonists, interleukins, systemic corticosteroids) within 24 weeks prior to study entry. NOTE A: Use of inhaled steroids, nasal steroids, topical steroids, or the equivalent of 10 mg of prednisone or less per day or a less than 2-week course of oral steroids is not exclusionary. NOTE B: A single course of 1% hydrocortisone cream applied up to 3 times a day to \<10 square inches area for \<2 weeks is permitted while on study. Use of all other topical steroids is excluded. * Known allergy/sensitivity or any hypersensitivity to components of the study drug or its formulation. * Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. * Serious illness requiring systemic treatment and/or hospitalization within 60 days prior to study entry. * Known cirrhosis or severe liver disease (e.g., ascites, encephalopathy, history of variceal bleeding). NOTE: Potential subjects with chronic hepatitis B or C virus infection who do not have known cirrhosis or severe liver disease may participate in the study. * Severe kidney disease (defined as estimated glomerular filtration rate \[GFR\] \<30 mL/min/1.73m2) at screening. * History of bowel obstruction or severe GI motility disorders including severe constipation. * Severe dysphagia or swallowing disorders. * Major GI tract surgery within 60 days prior to study entry. * Intent to initiate or change the dose of lipid-lowering drugs during study. NOTE: Potential subjects on stable doses of lipid-lowering agents (defined as no change in preparation or dose within 90 days prior to study entry) are permitted and may be enrolled. * Use of investigational therapies within 90 days prior to study entry unless permission was granted by the A5296 protocol chairs (see Study Management page). * Currently receiving hepatitis C therapy or anticipation that such therapy will be started during the study. * Use of probiotics, for more than 3 consecutive days within the 60 days prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endotoxin | baseline and Week 8 | Change in LPS from baseline to week 8, where baseline value is the average of pre-entry and entry values. |
| Change in Soluble CD14 (sCD14) | baseline and week 8 | Change in soluble CD14 (sCD14) from baseline to week 8, where baseline value is the average of pre-entry and entry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CD4+ T-cell Activation | baseline and week 8 | Change from baseline to week 8 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry |
| Change in CD8+ T-cell Activation | baseline and week 4 | Change from baseline to week 4 in CD8+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry |
| Change in Proportion of Cycling CD8+ | baseline and week 4 | Change from baseline to week 4 in cycling CD8+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry |
| Change in Proportion of Cycling CD4+ | baseline and week 4 | Change from baseline to week 4 in cycling CD4+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry |
| Change in Blood Phosphate Levels | from baseline to week 4 | Change in blood phosphate levels from baseline to week 4, where baseline value is the average of pre-entry and entry |
| Change in log10 HIV RNA Levels | baseline and week 4 | Change in log10 HIV RNA levels from baseline to week 4, where baseline value is the average of pre-entry and entry |
| Change in CD4+ T-cell Counts | baseline and week 4 | Change in CD4+ T-cell counts from baseline to week 4, where baseline is the average of pre-entry and entry |
| Change in IL-6 | baseline and week 4 | Changes in levels of systemic inflammation marker IL-6 from baseline to week 4, where baseline is the average of pre-entry and entry |
| Change in C-reactive Protein (CRP) | baseline and week 4 | Changes in levels of systemic inflammation marker CRP from baseline to week 4, where baseline is the average of pre-entry and entry |
| Change in Endotoxin | baseline and week 4 | Change in endotoxin from baseline to week 4, where baseline value is the average of pre-entry and entry |
| Change in D-dimer | baseline and week 4 | Change in levels of coagulation biomarker d-dimer from baseline to week 4, where baseline value is the average of pre-entry and entry |
| Change in Tissue Factor | baseline and week 4 | Change in levels of coagulation biomarker tissue factor from baseline to week 4, where baseline value is the average of pre-entry and entry |
| Change in Total Cholesterol | baseline and week 8 | Change in total cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry |
| Change in LDL Cholesterol | baseline and week 8 | Change in fasting LDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry |
| Change in HDL Cholesterol | baseline and week 8 | Change in fasting HDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry |
| Change in Non-HDL Cholesterol | baseline and week 8 | Change in non-HDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry |
| Change in Fasting Glucose | baseline and week 8 | Change in fasting glucose from baseline to week 8, where baseline value is the average of pre-entry and entry |
| Primary Adverse Events | baseline and week 16 | Number of subjects experiencing primary adverse events, defined as all reported Grade ≥ 2 signs and symptoms, Grade ≥ 2 laboratory abnormalities and other serious adverse events (SAEs) |
| Change in CRP | Baseline and Week 8 | Changes in levels of systemic inflammation marker CRP from baseline to week 8, where baseline is the average of pre-entry and entry |
| Change in sCD14 | baseline and week 4 | Change in sCD14 from baseline to week 4, where baseline value is the average of pre-entry and entry |
Countries
United States
Participant flow
Recruitment details
A5296 accrual opened under protocol version 1.0 on 11/21/11, and the first subject was enrolled on 12/29/11. Accrual to the study closed on 8/1/12, with a total of 40 subjects enrolled from 15 sites within the US.
Participants by arm
| Arm | Count |
|---|---|
| Sevelamer Carbonate Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | ART initiation | 1 |
| Overall Study | Loss to follow-up | 3 |
Baseline characteristics
| Characteristic | Sevelamer Carbonate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Age, Continuous | 44 years |
| CD4 count | 580 cells/mm^3 |
| Log10 HIV-1 RNA | 3.58 copies/mL |
| Race/Ethnicity, Customized Black Non-Hispanic | 24 participants |
| Race/Ethnicity, Customized Hispanic (regardless of Race) | 6 participants |
| Race/Ethnicity, Customized White non-Hispanic | 10 participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 40 |
| serious Total, serious adverse events | 2 / 40 |
Outcome results
Primary
Change in Endotoxin
Change in LPS from baseline to week 8, where baseline value is the average of pre-entry and entry values.
Time frame: baseline and Week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects had valid data at both baseline and week 8 and were included in primary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Endotoxin | 0.20 pg/mL |
p-value: 0.87Sign test
Primary
Change in Soluble CD14 (sCD14)
Change in soluble CD14 (sCD14) from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects had valid data at both baseline and week 8 and were included in primary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Soluble CD14 (sCD14) | -0.02 ug/mL |
p-value: 0.62Sign test
Secondary
Change in Blood Phosphate Levels
Change in blood phosphate levels from baseline to week 4, where baseline value is the average of pre-entry and entry
Time frame: from baseline to week 4
Population: Among 40 subjects enrolled in A5296, 39 subjects with valid data at both baseline and week 4 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Blood Phosphate Levels | 0 mg/dL |
Secondary
Change in Blood Phosphate Levels
Change in blood phosphate levels from week 8 to week 16
Time frame: from week 8 to week 16
Population: Among 40 subjects enrolled in A5296, 34 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Blood Phosphate Levels | 0.10 mg/dL |
Secondary
Change in Blood Phosphate Levels
Change in blood phosphate levels from baseline to week 8
Time frame: Baseline to Week 8
Population: Among 40 subjects enrolled in A5296, 37 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Blood Phosphate Levels | -0.1 mg/dL |
Secondary
Change in CD4+ T-cell Activation
Change from baseline to week 4 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 35 subjects with valid data at baseline and week 4 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD4+ T-cell Activation | 0.4 percentage |
Secondary
Change in CD4+ T-cell Activation
Change from baseline to week 8 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 33 subjects with valid data at baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD4+ T-cell Activation | 0.050 percentage |
Secondary
Change in CD4+ T-cell Activation
Change from week 8 to week 16 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 30 subjects with valid data at week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD4+ T-cell Activation | 0.45 percentage |
Secondary
Change in CD4+ T-cell Counts
Change in CD4+ T-cell counts from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD4+ T-cell Counts | -1 cells/mm^3 |
Secondary
Change in CD4+ T-cell Counts
Change in CD4+ T-cell counts from baseline to week 8, where baseline is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 36 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD4+ T-cell Counts | -14 cells/mm^3 |
Secondary
Change in CD4+ T-cell Counts
Change in CD4+ T-cell counts from baseline to week 4, where baseline is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 35 subjects with valid data at both baseline and week 4 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD4+ T-cell Counts | -25 cells/mm^3 |
Secondary
Change in CD8+ T-cell Activation
Change in CD8+ T-cell activation defined as the %CD38+/HLA-DR+ from baseline to week 8, where baseline is the average of pre-entry and entry
Time frame: Baseline and Week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 33 subjects with valid data at baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD8+ T-cell Activation | -0.450 percentage |
Secondary
Change in CD8+ T-cell Activation
Change from baseline to week 4 in CD8+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 35 subjects with valid data at baseline and week 4 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD8+ T-cell Activation | -0.05 percentage |
Secondary
Change in CD8+ T-cell Activation
Change in CD8+ T-cell activation defined as the %CD38+/HLA-DR+ from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 30 subjects with valid data at week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CD8+ T-cell Activation | -0.15 percentage |
Secondary
Change in C-reactive Protein (CRP)
Changes in levels of systemic inflammation marker CRP from baseline to week 4, where baseline is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects with valid data at both baseline and week 4 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in C-reactive Protein (CRP) | -141 ng/mL |
Secondary
Change in CRP
Changes in levels of systemic inflammation marker CRP from baseline to week 8, where baseline is the average of pre-entry and entry
Time frame: Baseline and Week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CRP | 45.5 ng/mL |
Secondary
Change in CRP
Changes in levels of systemic inflammation marker CRP from week 8 to week 16, where baseline is the average of pre-entry and entry
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in CRP | -34 ng/mL |
Secondary
Change in D-dimer
Change in levels of coagulation biomarker d-dimer from baseline to week 4, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects with valid data at both baseline and week 4 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in D-dimer | 5.95 ng/mL |
Secondary
Change in D-dimer
Change in levels of coagulation biomarker d-dimer from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in D-dimer | -17.15 ng/mL |
Secondary
Change in D-dimer
Change in levels of coagulation biomarker d-dimer from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in D-dimer | 20.30 ng/mL |
Secondary
Change in Endotoxin
Change in endotoxin from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 33 subjects with valid endpoint at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Endotoxin | -2.39 pg/mL |
Secondary
Change in Endotoxin
Change in endotoxin from baseline to week 4, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects had valid data at both baseline and week 4 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Endotoxin | 1.08 pg/mL |
Secondary
Change in Fasting Glucose
Change in fasting glucose from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects had valid data at both baseline and week 8 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Fasting Glucose | -2 mg/dL |
Secondary
Change in Fasting Glucose
Change in fasting glucose from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Fasting Glucose | 3.5 mg/dL |
Secondary
Change in HDL Cholesterol
Change in fasting HDL cholesterol from week 8 to week 16
Time frame: from week 8 to week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 33 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in HDL Cholesterol | 1 mg/dL |
Secondary
Change in HDL Cholesterol
Change in fasting HDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 35 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in HDL Cholesterol | 0.50 mg/dL |
Secondary
Change in IL-6
Changes in levels of systemic inflammation marker IL-6 from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in IL-6 | 0.19 pg/mL |
Secondary
Change in IL-6
Changes in levels of systemic inflammation marker IL-6 from baseline to week 4, where baseline is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All subjects had valid data at both baseline and week 4 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in IL-6 | 0.28 pg/mL |
Secondary
Change in IL-6
Changes in levels of systemic inflammation marker IL-6 from baseline to week 8, where baseline is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in IL-6 | -0.02 pg/mL |
Secondary
Change in LDL Cholesterol
Change in fasting LDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in LDL Cholesterol | -18.25 mg/dL |
Secondary
Change in LDL Cholesterol
Change in fasting LDL cholesterol from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 32 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in LDL Cholesterol | 14.20 mg/dL |
Secondary
Change in log10 HIV RNA Levels
Change in log10 HIV RNA levels from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in log10 HIV RNA Levels | 0.16 log10(copies/mL) |
Secondary
Change in log10 HIV RNA Levels
Change in log10 HIV RNA levels from baseline to week 4, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects had valid data at both baseline and week 4 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in log10 HIV RNA Levels | 0.02 log10(copies/mL) |
Secondary
Change in log10 HIV RNA Levels
Change in log10 HIV RNA levels from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects had valid data at both baseline and week 8 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in log10 HIV RNA Levels | -0.02 log10(copies/mL) |
Secondary
Change in Non-HDL Cholesterol
Change in non-HDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 35 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Non-HDL Cholesterol | -12 mg/dL |
Secondary
Change in Non-HDL Cholesterol
Change in non-HDL cholesterol from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 33 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Non-HDL Cholesterol | 4 mg/dL |
Secondary
Change in Proportion of Cycling CD4+
Change from week 8 to week 16 in cycling CD4+ , defined as the %Ki67+
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 29 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Proportion of Cycling CD4+ | 0.2 percentage |
Secondary
Change in Proportion of Cycling CD4+
Change from baseline to week 4 in cycling CD4+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects had valid data at both baseline and week 4 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Proportion of Cycling CD4+ | 0.125 percentage |
Secondary
Change in Proportion of Cycling CD4+
Change from baseline to week 8 in cycling CD4+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 32 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Proportion of Cycling CD4+ | 0.025 percentage |
Secondary
Change in Proportion of Cycling CD8+
Change from week 8 to week 16 in cycling CD8+ , defined as the %Ki67+
Time frame: from week 8 to week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 29 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Proportion of Cycling CD8+ | 0.300 percentage |
Secondary
Change in Proportion of Cycling CD8+
Change from baseline to week 4 in cycling CD8+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects have valid data at baseline and week 4 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Proportion of Cycling CD8+ | -0.125 percentage |
Secondary
Change in Proportion of Cycling CD8+
Change from baseline to week 8 in cycling CD8+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 32 subjects with valid data at baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Proportion of Cycling CD8+ | 0.1 percentage |
Secondary
Change in sCD14
Change in sCD14 from baseline to week 4, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects have valid data at baseline and week 4 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in sCD14 | -0.09 ug/mL |
Secondary
Change in sCD14
Change in sCD14 from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects had valid data at both week 8 and week 16 and were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in sCD14 | 0.06 ug/mL |
Secondary
Change in Tissue Factor
Change in levels of coagulation biomarker tissue factor from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects had valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Tissue Factor | -2 pg/mL |
Secondary
Change in Tissue Factor
Change in levels of coagulation biomarker tissue factor from baseline to week 4, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 4
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. All 36 subjects with valid data at both baseline and week 4 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Tissue Factor | -2.47 pg/mL |
Secondary
Change in Tissue Factor
Change in levels of coagulation biomarker tissue factor from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 34 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Tissue Factor | 3.8 pg/mL |
Secondary
Change in Total Cholesterol
Change in total cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Time frame: baseline and week 8
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 35 subjects with valid data at both baseline and week 8 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Total Cholesterol | -12.5 mg/dL |
Secondary
Change in Total Cholesterol
Change in total cholesterol from week 8 to week 16
Time frame: week 8 and week 16
Population: This is an as-treated analysis, limited to 36 subjects who have data for baseline and week 8 and who remain on study treatment through week 8. Among these 36 subjects, 33 subjects with valid data at both week 8 and week 16 were included in this secondary analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sevelamer Carbonate | Change in Total Cholesterol | 9 mg/dL |
Secondary
Primary Adverse Events
Number of subjects experiencing primary adverse events, defined as all reported Grade ≥ 2 signs and symptoms, Grade ≥ 2 laboratory abnormalities and other serious adverse events (SAEs)
Time frame: baseline and week 16
Population: All 40 subjects enrolled in A5296 were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sevelamer Carbonate | Primary Adverse Events | 28 participants |