HIV-1 Infection
Conditions
Keywords
Sitagliptin, Inflammation, Immune activation, Viral suppression, HIV-1, Immunology biomarkers, sCD14
Brief summary
The purpose of the study is to evaluate whether sitagliptin (Januvia is the brand name for sitagliptin) reduces inflammation and immune activation markers in HIV-infected men and women when compared to a placebo (inactive medication like a dummy pill). The study evaluated whether taking 100 mg of sitagliptin by mouth daily for 16 weeks is safe and effective for HIV-infected persons on antiretroviral therapy (ART) who do not have diabetes. Sitagliptin is a medication that is used to treat people with diabetes (high blood sugar) but also may reduce inflammation in the body.
Detailed description
ACTG A5346 is a phase II, randomized, double-blinded, placebo-controlled, trial of sitagliptin 100 mg vs. placebo for 16 weeks followed by a 4-week post-intervention follow-up. A5346 studied whether sitagliptin reduced plasma concentrations of sCD14 in HIV-infected men and women ≥18 years of age who were on suppressive ART with HIV-1 RNA below the limit of quantification at screening and for at least the prior 48 weeks. Participants were randomized 1:1 to Sitagliptin arm vs. Placebo arm, and were stratified by screening CD4 count (100-350 vs. \>350 cells/mm\^3) and statin use (on statins vs. not on statins).
Interventions
DRUGSitagliptin
100 mg one tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up
One tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up.
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
* Documented HIV-1 infection. * Currently on an antiretroviral regimen consisting of at least 2 NRTIs and either a protease inhibitor boosted with low dose ritonavir, an integrase inhibitor, or an NNRTI. (Other ART regimens may be acceptable. Sites must consult the protocol team for approval) * Currently on continuous ART for ≥48 weeks prior to study entry with no interruption longer than 7 consecutive days during that period. * Plasma HIV-1 RNA levels below 75 copies/mL for at least 48 weeks prior to study entry. The participant must have a minimum of two values in the last 48 weeks obtained \>30 days apart, with the most recent value obtained within 90 days prior to entry. (Single determinations that are between the assay quantification limit and 500 copies/mL (i.e., blips) are allowed as long as the preceding and subsequent determinations are below the level of quantification). * CD4+ cell count ≥100 cells/mm\^3 obtained within 90 days prior to study entry. * The following laboratory values obtained within 90 days prior to entry. * Absolute neutrophil count (ANC) ≥750/mm\^3 * Hemoglobin ≥8.0 g/dL * Platelet count ≥50,000/mm\^3 * Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockroft-Gault formula NOTE: Calculation for the Cockcroft-Gault equation is available at https://www.fstrf.org/apps/cfmx/apps/common/Portal/index.cfm * Aspartate aminotransferase (AST) (SGOT) ≤5 x upper limit of normal (ULN). * alanine aminotransferase (ALT) (SGPT) ≤5 x ULN. * alkaline phosphatase ≤5 x ULN. * Total bilirubin ≤2.5 x ULN (if the participant is receiving atazanavir, a total bilirubin of ≤5 x ULN is acceptable). * Hemoglobin A1C ≤6.5% * For females of reproductive potential, adequate contraception. * Karnofsky performance score ≥70 within 90 days prior to entry. * Ability and willingness of participant or legal guardian/representative to provide informed consent. * Participants on statin therapy must be stable on the same dose for at least the prior 12 weeks with no anticipated change in statin or dose during the intervention.
Exclusion criteria
* Change in the ART regimen within the 12 weeks prior to study entry, or anticipated/intended modification of ART during the study period. * Two or more HIV-1 RNA determinations \>200 copies/mL within the 48 week period prior to study entry. * History of clinical pancreatitis or diabetes mellitus diagnosed by a medical provider. * Acute or chronic liver disease with evidence of cirrhosis or portal hypertension. * Chronic hepatitis C (defined as HCV antibody positive and HCV RNA detectable). * History of chronic hepatitis B (defined as surface antibody negative, surface antigen positive, and/or HBV DNA detectable). * Use of any immunomodulator, HIV vaccine, investigational therapy, or anti-TNF therapies within 90 days prior to study entry. * Active malignancy with expected need for systemic chemotherapy or radiation therapy during the study period. * Use of human growth hormone, tesamorelin, testosterone or anabolic steroids within 90 days prior to study entry (except chronic, stable, replacement dosages in men with diagnosed hypogonadism is allowed). * Pregnant or breastfeeding. * Use of any anti-diabetic medication or GLP-1 analogues within the 12 weeks prior to study entry. * Current diagnosis of congestive heart failure. * 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. * Acute or serious illness requiring systemic treatment and/or hospitalization within 90 days prior to entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in sCD14 From Baseline to Week 15/16 | Pre-entry, Week 0, Week 15, Week 16 | sCD14 (soluble cluster of differentiation 14) is a biomarker of gut microbial translocation and monocyte/macrophage activation. The outcome measures are changes in log10 transformed sCD14 from baseline to week 15/16 (week 15/16 - baseline) Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 15 and week 16 were averaged for week 15/16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in sCD163 | Week 0, week 15, week 20 | sCD163 (soluble CD 163) is a marker of macrophage activation and arterial inflammation. Change in log10 transformed sCD163 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15). |
| Change in sCD26 | Week 0, week 15, week 20 | sCD26 (soluble cluster of differentiation 26) is an enzyme that metabolizes DPP-4 (dipeptidyl peptidase-4), an enzyme that is inhibited by sitagliptin. Change in log10 transformed sCD26 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15). |
| Change in IL-6 | Week 0, week 15, week 20 | IL-6 (Interleukin-6) is a biomarker of systemic inflammation. Change in log10 transformed IL-6 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15). |
| Change in hsCRP | Week 0, week 15, week 20 | hsCRP (high-sensitivity C-reactive protein) is a biomarker of inflammation. Change in log10 transformed hsCRP from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15). |
| Change in sTNF-r1 | Week 0, week 15, week 20 | sTNF-r1 (soluble tumour necrosis alpha receptor 1) is a biomarker of inflammation. Change in log10 transformed sTNF-r1 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15). |
| Change in sTNF-r2 | Week 0, week 15, week 20 | sTNF-r2 (soluble tumour necrosis alpha receptor 2) is a biomarker of inflammation. Change in log10 transformed sTNF-r2 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15). |
| Change in IP-10 | Week 0, week 15, week 20 | IP-10 (also known as CXCL10) is a biomarker implicated in cardiovascular disease. Change in log10 transformed IP-10 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15). |
| Change in sCD14 From Week 15/16 to Week 20 | Week 15, week 16, week 20 | sCD14 (soluble cluster of differentiation 14) is a biomarker of gut microbial translocation and monocyte/macrophage activation. The outcome measures are changes in log10 transformed sCD14 from week 15/16 to week 20 (week 20 - week 15/16). Levels measured at week 15 and week 16 were averaged for week 15/16. |
| Change in CD4+ T-cell Activation | Week 0, week 15, week 20 | Level of CD4+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+. The endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed. |
| Change in CD8+ T-cell Activation | Week 0, week 15, week 20 | Level of CD8+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+. The endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed. |
| Change in %CD14+/CD16- (Classical Monocytes) | Week 0, week 15, week 20 | CD14+/CD16- is the percentage of cells that expressed CD14 and low CD16 in total monocytes (also known as classical monocytes). This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of November 2017. The study team prioritized completion of the soluble markers (including the primary outcome measure), which are reported herein, over the completion of the cellular markers. Results will be entered once the data is complete and analyzed. |
| Change in %CD14+/CD16+ (Intermediate Monocytes) | Week 0, week 15, week 20 | %CD14+/CD16+ is the percentage of cells that expressed both CD14 and CD16 in total monocytes (also known as intermediate monocytes). This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed. |
| Change in %CD14dim/CD16++ (Non-classical Monocytes) | Week 0, week 15, week 20 | %CD14dim/CD16++ is the percentage of cells that expressed low levels of CD14dim and high levels of CD16++ in total monocytes (also known as non-classical monocytes). This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed. |
| Number of Participants With Grade ≥2 Adverse Events Related to Study Drug | From study entry to end of study (Week 20) | The DAIDS Adverse Event Grading Table, Version 2.0, was used for grading of AEs |
| Change in CD4+/CD8+ T-cell Ratio | Week 0 and week 15 | CD4+/CD8+ T-cell ratio change from week 0 to week 15 (week 15 - week 0). Note that CD4 and CD8 were not evaluated at week 20 in this study. |
Countries
United States
Participant flow
Recruitment details
First participant was enrolled on October 20, 2015. Accrual to the study closed on August 24, 2016, with 15 U.S sites registered and enrolled participants.
Pre-assignment details
Participants were randomized 1:1 to Sitagliptin and Placebo arms. Randomization was stratified by screening CD4 (100-350 vs \>350 cells/mm\^3) and statin use.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Arm Sitagliptin: 100 mg one tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up | 45 |
| Placebo Arm Placebo for sitagliptin: One tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up. | 45 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Not being able to get to clinic | 1 | 0 |
Baseline characteristics
| Characteristic | Sitagliptin Arm | Placebo Arm | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 50 years | 51 years |
| Age, Customized 18-39 years | 11 Participants | 6 Participants | 17 Participants |
| Age, Customized 40-59 years | 27 Participants | 32 Participants | 59 Participants |
| Age, Customized >=60 years | 7 Participants | 7 Participants | 14 Participants |
| Baseline sCD14 | 6.39 log10 pg/mL | 6.38 log10 pg/mL | 6.39 log10 pg/mL |
| CD4 count | 609 cells/mm^3 | 551 cells/mm^3 | 586 cells/mm^3 |
| IV drug use Never | 44 Participants | 42 Participants | 86 Participants |
| IV drug use Previously | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic (Regardless of Race) | 7 Participants | 7 Participants | 14 Participants |
| Race/Ethnicity, Customized more than one race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 15 Participants | 19 Participants | 34 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 23 Participants | 18 Participants | 41 Participants |
| Region of Enrollment United States | 45 Participants | 45 Participants | 90 Participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 38 Participants | 36 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 45 |
| other Total, other adverse events | 20 / 45 | 24 / 45 |
| serious Total, serious adverse events | 1 / 45 | 2 / 45 |
Outcome results
Primary
Change in sCD14 From Baseline to Week 15/16
sCD14 (soluble cluster of differentiation 14) is a biomarker of gut microbial translocation and monocyte/macrophage activation. The outcome measures are changes in log10 transformed sCD14 from baseline to week 15/16 (week 15/16 - baseline) Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 15 and week 16 were averaged for week 15/16.
Time frame: Pre-entry, Week 0, Week 15, Week 16
Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitagliptin Arm | Change in sCD14 From Baseline to Week 15/16 | -0.03 log10 pg/mL |
| Placebo Arm | Change in sCD14 From Baseline to Week 15/16 | -0.03 log10 pg/mL |
Comparison: Null hypothesis: There is no difference between the two arms in the change in sCD14 from baseline to week 15/16.p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Change in %CD14+/CD16- (Classical Monocytes)
CD14+/CD16- is the percentage of cells that expressed CD14 and low CD16 in total monocytes (also known as classical monocytes). This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of November 2017. The study team prioritized completion of the soluble markers (including the primary outcome measure), which are reported herein, over the completion of the cellular markers. Results will be entered once the data is complete and analyzed.
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in %CD14+/CD16- (Classical Monocytes) | change from baseline to week 15 | -2.30 percentage of cells |
| Sitagliptin Arm | Change in %CD14+/CD16- (Classical Monocytes) | change from week 15 to week 20 | 0.40 percentage of cells |
| Placebo Arm | Change in %CD14+/CD16- (Classical Monocytes) | change from baseline to week 15 | -0.80 percentage of cells |
| Placebo Arm | Change in %CD14+/CD16- (Classical Monocytes) | change from week 15 to week 20 | -1.00 percentage of cells |
Secondary
Change in %CD14+/CD16+ (Intermediate Monocytes)
%CD14+/CD16+ is the percentage of cells that expressed both CD14 and CD16 in total monocytes (also known as intermediate monocytes). This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed.
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in %CD14+/CD16+ (Intermediate Monocytes) | change from baseline to week 15 | 0.87 percentage of cells |
| Sitagliptin Arm | Change in %CD14+/CD16+ (Intermediate Monocytes) | change from week 15 to week 20 | -0.65 percentage of cells |
| Placebo Arm | Change in %CD14+/CD16+ (Intermediate Monocytes) | change from baseline to week 15 | -0.12 percentage of cells |
| Placebo Arm | Change in %CD14+/CD16+ (Intermediate Monocytes) | change from week 15 to week 20 | -0.19 percentage of cells |
Secondary
Change in %CD14dim/CD16++ (Non-classical Monocytes)
%CD14dim/CD16++ is the percentage of cells that expressed low levels of CD14dim and high levels of CD16++ in total monocytes (also known as non-classical monocytes). This endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed.
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in %CD14dim/CD16++ (Non-classical Monocytes) | change from baseline to week 15 | 0.31 percentage of cells |
| Sitagliptin Arm | Change in %CD14dim/CD16++ (Non-classical Monocytes) | change from week 15 to week 20 | -0.37 percentage of cells |
| Placebo Arm | Change in %CD14dim/CD16++ (Non-classical Monocytes) | change from baseline to week 15 | -0.03 percentage of cells |
| Placebo Arm | Change in %CD14dim/CD16++ (Non-classical Monocytes) | change from week 15 to week 20 | 0.12 percentage of cells |
Secondary
Change in CD4+/CD8+ T-cell Ratio
CD4+/CD8+ T-cell ratio change from week 0 to week 15 (week 15 - week 0). Note that CD4 and CD8 were not evaluated at week 20 in this study.
Time frame: Week 0 and week 15
Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitagliptin Arm | Change in CD4+/CD8+ T-cell Ratio | 0.00 ratio |
| Placebo Arm | Change in CD4+/CD8+ T-cell Ratio | 0.02 ratio |
Secondary
Change in CD4+ T-cell Activation
Level of CD4+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+. The endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed.
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in CD4+ T-cell Activation | change from baseline to week 15 | 0.12 percentage of cells |
| Sitagliptin Arm | Change in CD4+ T-cell Activation | change from week 15 to week 20 | 0.07 percentage of cells |
| Placebo Arm | Change in CD4+ T-cell Activation | change from baseline to week 15 | 0.08 percentage of cells |
| Placebo Arm | Change in CD4+ T-cell Activation | change from week 15 to week 20 | 0.06 percentage of cells |
Secondary
Change in CD8+ T-cell Activation
Level of CD8+ T-cell activation was determined by measuring the percentage of cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+. The endpoint is measuring the change from week 0 to week 15 (week 15 - week 0) and change from week 15 to week 20 (week 20 - week 15). Data for cellular markers are not available as of December 2017. These data are based on immunology assays which were tested in batch to minimize variability. Due to batch testing, shipment of samples for testing could not begin until after the study follow-up completion, which was 1 month after the primary complete date. Please note that these secondary outcomes were not included in the primary analyses. There are many outcomes in this study and the immunology lab had to give priority to the assays planned to be included in the primary manuscript. Results will be entered once the data is complete and analyzed.
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in CD8+ T-cell Activation | change from baseline to week 15 | 0.03 percentage of cells |
| Sitagliptin Arm | Change in CD8+ T-cell Activation | change from week 15 to week 20 | 0.11 percentage of cells |
| Placebo Arm | Change in CD8+ T-cell Activation | change from baseline to week 15 | -0.27 percentage of cells |
| Placebo Arm | Change in CD8+ T-cell Activation | change from week 15 to week 20 | -0.29 percentage of cells |
Secondary
Change in hsCRP
hsCRP (high-sensitivity C-reactive protein) is a biomarker of inflammation. Change in log10 transformed hsCRP from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in hsCRP | Change from week 15 to week 20 | -0.02 log10 ng/mL |
| Sitagliptin Arm | Change in hsCRP | Change from week 0 to week 15 | -0.08 log10 ng/mL |
| Placebo Arm | Change in hsCRP | Change from week 0 to week 15 | -0.05 log10 ng/mL |
| Placebo Arm | Change in hsCRP | Change from week 15 to week 20 | -0.01 log10 ng/mL |
Secondary
Change in IL-6
IL-6 (Interleukin-6) is a biomarker of systemic inflammation. Change in log10 transformed IL-6 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in IL-6 | Change from week 0 to week 15 | 0.00 log10 pg/mL |
| Sitagliptin Arm | Change in IL-6 | Change from week 15 to week 20 | -0.06 log10 pg/mL |
| Placebo Arm | Change in IL-6 | Change from week 0 to week 15 | 0.00 log10 pg/mL |
| Placebo Arm | Change in IL-6 | Change from week 15 to week 20 | 0.01 log10 pg/mL |
Secondary
Change in IP-10
IP-10 (also known as CXCL10) is a biomarker implicated in cardiovascular disease. Change in log10 transformed IP-10 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in IP-10 | Change from week 0 to week 15 | -0.31 log10 pg/mL |
| Sitagliptin Arm | Change in IP-10 | Change from week 15 to week 20 | 0.23 log10 pg/mL |
| Placebo Arm | Change in IP-10 | Change from week 0 to week 15 | -0.01 log10 pg/mL |
| Placebo Arm | Change in IP-10 | Change from week 15 to week 20 | 0.02 log10 pg/mL |
Secondary
Change in sCD14 From Week 15/16 to Week 20
sCD14 (soluble cluster of differentiation 14) is a biomarker of gut microbial translocation and monocyte/macrophage activation. The outcome measures are changes in log10 transformed sCD14 from week 15/16 to week 20 (week 20 - week 15/16). Levels measured at week 15 and week 16 were averaged for week 15/16.
Time frame: Week 15, week 16, week 20
Population: As-treated population limited to participants who had baseline and week 15/16 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitagliptin Arm | Change in sCD14 From Week 15/16 to Week 20 | 0.04 log10 pg/mL |
| Placebo Arm | Change in sCD14 From Week 15/16 to Week 20 | 0.02 log10 pg/mL |
Secondary
Change in sCD163
sCD163 (soluble CD 163) is a marker of macrophage activation and arterial inflammation. Change in log10 transformed sCD163 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in sCD163 | Change from week 0 to week 15 | -0.03 log10 ng/mL |
| Sitagliptin Arm | Change in sCD163 | Change from week 15 to week 20 | 0.01 log10 ng/mL |
| Placebo Arm | Change in sCD163 | Change from week 0 to week 15 | -0.02 log10 ng/mL |
| Placebo Arm | Change in sCD163 | Change from week 15 to week 20 | 0.00 log10 ng/mL |
Secondary
Change in sCD26
sCD26 (soluble cluster of differentiation 26) is an enzyme that metabolizes DPP-4 (dipeptidyl peptidase-4), an enzyme that is inhibited by sitagliptin. Change in log10 transformed sCD26 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in sCD26 | Change from week 0 to week 15 | -0.16 log10 ng/mL |
| Sitagliptin Arm | Change in sCD26 | Change from week 15 to week 20 | 0.08 log10 ng/mL |
| Placebo Arm | Change in sCD26 | Change from week 0 to week 15 | -0.16 log10 ng/mL |
| Placebo Arm | Change in sCD26 | Change from week 15 to week 20 | 0.04 log10 ng/mL |
Secondary
Change in sTNF-r1
sTNF-r1 (soluble tumour necrosis alpha receptor 1) is a biomarker of inflammation. Change in log10 transformed sTNF-r1 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in sTNF-r1 | Change from week 0 to week 15 | -0.01 log10 pg/mL |
| Sitagliptin Arm | Change in sTNF-r1 | Change from week 15 to week 20 | 0.00 log10 pg/mL |
| Placebo Arm | Change in sTNF-r1 | Change from week 0 to week 15 | -0.04 log10 pg/mL |
| Placebo Arm | Change in sTNF-r1 | Change from week 15 to week 20 | -0.01 log10 pg/mL |
Secondary
Change in sTNF-r2
sTNF-r2 (soluble tumour necrosis alpha receptor 2) is a biomarker of inflammation. Change in log10 transformed sTNF-r2 from Week 0 to week 15 (week 15 - week 0), and from week 15 to week 20 (week 20 - week 15).
Time frame: Week 0, week 15, week 20
Population: As-treated population limited to participants who had baseline and week 15 measurements, completed study treatment with no more than 34 cumulative days of treatment interruption, did not use prohibited medications, did not have a confirmed virologic failure at or prior to week 16 (see protocol 6.2.3).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sitagliptin Arm | Change in sTNF-r2 | Change from week 0 to week 15 | -0.05 log10 pg/mL |
| Sitagliptin Arm | Change in sTNF-r2 | Change from week 15 to week 20 | 0.06 log10 pg/mL |
| Placebo Arm | Change in sTNF-r2 | Change from week 0 to week 15 | -0.06 log10 pg/mL |
| Placebo Arm | Change in sTNF-r2 | Change from week 15 to week 20 | 0.05 log10 pg/mL |
Secondary
Number of Participants With Grade ≥2 Adverse Events Related to Study Drug
The DAIDS Adverse Event Grading Table, Version 2.0, was used for grading of AEs
Time frame: From study entry to end of study (Week 20)
Population: All enrolled participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin Arm | Number of Participants With Grade ≥2 Adverse Events Related to Study Drug | 3 Participants |
| Placebo Arm | Number of Participants With Grade ≥2 Adverse Events Related to Study Drug | 0 Participants |