DPPIVinHIV: Dipeptidyl Peptidase-4 Inhibition and Immune Function in HIV

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01093651
• Collaborator: The Campbell Foundation (Other)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

We will test the safety of a new class of anti-diabetes compounds (DPPIV-inhibitors) in people living with HIV. Future trials will examine efficacy for treating diabetes and reducing cardiovascular disease risk in people living with HIV.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Insulin Resistance	Drug: Sitagliptin; Drug: Placebo	Phase 2/Phase 3

Detailed Description

Human immunodeficiency virus (HIV)-infection and treatment with antiretroviral therapies are associated with several cardiometabolic risk factors; insulin resistance, diabetes, dyslipidemia, central adiposity, that increase risk for MI and stroke. A new class of drugs used to treat type 2 diabetes has been introduced; Dipeptidyl peptidase-IV (DPPIV)-inhibitors (Januvia®, Onglyza®, alogliptin). Dipeptidyl peptidase-IV (DPPIV)-inhibition could be a safe and effective therapy for HIV-associated insulin resistance and diabetes. However, no safety data exist. The research question is: If HIV+ adults with stable immunologic (CD4+ T-cell count >350 cells/μL) and virologic (plasma HIV RNA <50 copies/mL) function are given a DPPIV-inhibitor would their CD4+ T-cell count and plasma HIV RNA level increase, decrease, or stay the same? Theoretically, DPPIV-inhibition could enhance their immune system by increasing SDF-1α levels; a potent inhibitor of HIV-entry into T-cells, or harm the HIV+ immune system by inactivating CD26 on immune cells. We hypothesize that DPPIV-inhibition will not harm the immune system in HIV+ people. We propose a blinded randomized controlled pilot safety trial of an FDA-approved DPPIV-inhibitor in virologically- and immunologically-stable HIV+ men and women. We will monitor CD4+ T-cell count, plasma HIV RNA levels, immune activation markers, and safety outcomes (lipid/lipoprotein profiles, blood pressure, kidney and liver function) during 4-6 months of DPPIV-inhibitor exposure vs placebo in 20 HIV+ adults. If safety is confirmed, the efficacy of DPPIV-inhibition in HIV+ with insulin resistance will be tested in future trials that examine potential glucoregulatory and cardiovascular benefits.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Official Title: A Blinded Randomized Controlled Pilot Immunologic and Virologic Safety Trial of an FDA-approved DPPIV-inhibitor in HIV+ Men and Women
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DPPIV inhibition Four to six months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status.	Drug: Sitagliptin; 100 mg sitagliptin daily for 4-6 months
Placebo Comparator: Placebo Four to six months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status.	Drug: Placebo; Daily placebo for 4-6 months

Outcome Measures

Primary Outcome Measures

1. CD4+ T-cell Count [Monthly for 4 months]

2. Plasma HIV Viremia (Viral Load) [Monthly for 6 months]

   Percentage of participants with plasma HIV RNA copy number less than 48 copies/mL

Secondary Outcome Measures

1. Soluble TNFR2; Serum Biomarkers of Immune Activation [Baseline, week 8, week 16]

   serum soluble tumor necrosis factor receptor-2 concentration

2. SDF1α; Serum Biomarkers of Immune Activation [Baseline, week 8, week 16]

   serum stromal cell-derived factor-1α concentration

3. RANTES; Serum Biomarkers of Immune Activation [Baseline, week 8, week 16]

   serum Regulated on Activation, Normal T cell Expressed and Secreted concentration

4. Oral Glucose Tolerance [Baseline, week 8, week 16]

   Area under the 75-gr oral glucose tolerance curve (AUCg) based on plasma glucose values measured at 0, 30, 60, 90, and 120 mins post-glucose challenge.

5. Self-reported Symptoms [Monthly for 4 months]

   Cumulative number of self-reported symptoms based on the Division of AIDS Grading Scale for the Severity of Adult Adverse Events (0-4 scale where 0 is no new symptoms, 4 is serious adverse event or toxicity)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Thirty 18-65 yr old HIV-infected men and women (with source documentation of HIV status) who are stable on any antiretroviral therapy (cART) regimen

2. Have stable (at least the past 12-months) immunologic (>350 CD4+ T-cells/µL) and virologic (<50 copies HIV RNA/mL) status.

3. BMI 18-42kg/m2;

4. Normal blood chemistry for at least 1 month prior to enrollment;

5. Platelet count > 30,000/mm3, absolute neutrophil count >750/mm3, transaminases < 2.5x the upper limit of normal (ULN).

6. Long-term non-progressors (not on ART) are not eligible.

Exclusion Criteria:

1. CD4+ T-cell count <350 cells/µL or detectable plasma HIV RNA (>50 copies HIV RNA/mL) within the past 12-months. During the study, if CD4+ T-cell count declines by >100 cells/µL, or if plasma HIV RNA becomes detectable (>50 copies HIV RNA/mL after repeat analysis 2wks apart), and the participant denies any lapse in their anti-HIV medication regimen, the study medication will be stopped and an adverse event documented. If at any time during the study, two participants experience a reduction in T-cell count >100 cells/µL, or their plasma HIV RNA levels become detectable (>50 copies HIV RNA/mL after repeat analysis 2wks apart), and they are confirmed (by unblinding) to have received sitagliptin, the study will be stopped for serious safety concerns.

2. Systemic, secondary or opportunistic infection within past 12-months.

3. Fasting glucose intolerance (FBG >100mg/dL), fasting hyperinsulinemia (>15µU/mL), or fasting insulin resistance (Homeostasis model for insulin resistance (HOMA) >3.0). Any agents that might alter glucose metabolism (insulin, TZDs, metformin, glucocorticoids, sulfonylurea, corticosteroids, megace, rhGH, GH-secretagogue) during the 3 months prior to enrollment or at any time during enrollment. Volunteers with T2DM, IDDM or diabetic ketoacidosis will not be enrolled.

4. History of serious CV disease or NYHA Functional Class III or IV, (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, valve disease (murmur), stroke, uncontrolled high blood pressure (resting >160/95 mmHg), irregular heart rhythm, resting ST-segment depression >1mm). Treatment with medications for a CV condition (cardiac glycosides α- or ß-blockers). Some antihypertensive medications (calcium-channel blocker, diuretic, angiotensin II receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACE)) will be permitted.

5. Moderate to severe renal insufficiency. Serum creatinine >1.7 mg/dL (men) >1.5 mg/dL (women).

6. Known allergy or hypersensitivity to DPPIV-inhibitors.

7. Plan to change anti-HIV medication regimen or prophylaxis for opportunistic infection within 6-months of starting study.Transitions among efavirenz-based regimens will be allowed (e.g., Efavirenz + lamivudine + zidovudine (combivir) to Efavirenz + emtricitabine + tenofovir (Atripla)).

8. Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 3 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period.

9. Chronic hepatitis B infection (HB surface antigen positive). Active hepatitis C infection (detectable Hep C RNA). Those who have cleared hepatitis B or C infection are eligible.

10. Hematocrit <34% in men or <25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin <10 gm/100ml with symptoms.

11. Nausea, vomiting, diarrhea (>4 loose stools/day) that are unresponsive to treatment. History of eating disorder or significant GI-disease.

12. Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If birth control pills are used, the woman must be stable on these medications for at least 6 months prior to enrollment.

13. Active malignancy or treatment with chemotherapeutic agents or radiation therapy (within past 12 months).

14. 10% unintentional body weight loss during the 12 months prior to enrollment.

15. "Blinded" investigational drugs/medications during the 3 months prior to enrollment that will not be unblinded before enrollment. Open-label investigational drugs are permitted (within past 3 months, no plan to stop during enrollment and not known to affect glucose, lipid, adipose tissue or liver metabolism).

16. Over the counter agents that might alter glucose, lipid, or adipose tissue metabolism (e.g., creatine monohydrate, chromium picolinate, amino acid/protein supplements, medium- or long-chain fatty acids) within 1 month of enrollment. These supplements are not permitted during the treatment period.

17. Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded.

18. Active substance abuse that the physician-scientist believes may compromise safety, compliance, or interfere with study drug or data interpretation.

19. Any cytokine or anti-cytokine therapy during 3 months prior to enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• The Campbell Foundation

Investigators

• Principal Investigator: Kevin E Yarasheski, PhD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kevin Yarasheski, PhD, Professor of Medicine, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01093651
• Other Study ID Numbers: KEY03222010
• First Posted: Mar 26, 2010
• Last Update Posted: Feb 17, 2014
• Last Verified: Jan 1, 2014

• Additional relevant MeSH terms: Insulin Resistance; Sitagliptin Phosphate

Study Results

Participant Flow

Recruitment Details	HIV-infected adults (18 - 65 years old) were recruited from the AIDS Clinical Trials Unit and the Infectious Diseases Clinic at Washington University School of Medicine. Thirty-one candidates were screened and 20 were enrolled; all participants were HIV positive but were otherwise healthy with stable immunologic and virologic status on HAART.
Pre-assignment Detail	Twenty participants were randomized to n=10 placebo or n=10 sitagliptin (Januvia(R)). Eleven volunteers were screened and found ineligible (see eligibility criteria), or did not choose to participate in the study.

Arm/Group Title	Placebo	DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	DPPIV Inhibition	Total
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40 (15)	36 (9)	38 (12)
Sex: Female, Male (Count of Participants)
Female	2 20%	1 10%	3 15%
Male	8 80%	9 90%	17 85%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	CD4+ T-cell Count
Time Frame	Monthly for 4 months

Outcome Measure Data

Analysis Population Description

CD4+ T-cell count

Arm/Group Title	Placebo	DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
Measure Participants	10	10
Baseline	602 (91)	648 (185)
Week 4	689 (153)	750 (225)
Week 8	696 (194)	656 (207)
Week 12	686 (167)	706 (168)
Week 16	681 (151)	636 (173)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DPPIV Inhibition
	Comments	The main effect analysis was applied to both rows (timepoint) and categories (groups). It used linear mixed models to simultaneously assess differences in CD4+ T-cell count between the DPP4 inhibitor and placebo groups (categories) over time (rows). Pairwise post-hoc contrasts were performed to assess the between and within group differences in outcome measures at each time point.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	The a priori threshold for statistical significance was p<0.05. The main effect analysis for CD4+ T-cell count over time and between the 2 groups did not achieve p<0.05 (not statistically significant).
	Method	Mixed Models Analysis
	Comments	Study subject was included in these models as a random variable to account for within-participant correlation.

2. Primary Outcome

Title	Plasma HIV Viremia (Viral Load)
Description	Percentage of participants with plasma HIV RNA copy number less than 48 copies/mL
Time Frame	Monthly for 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
Measure Participants	10	10
Baseline	100 1000%	100 1000%
Week 4	100 1000%	100 1000%
Week 8	100 1000%	100 1000%
Week 12	100 1000%	100 1000%
Week 16	100 1000%	100 1000%
Week 24	100 1000%	100 1000%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DPPIV Inhibition
	Comments	The main effect analysis was applied to both rows (timepoint) and categories (groups). It used linear mixed models to simultaneously assess differences in plasma HIV RNA copy number/mL between the DPP4 inhibitor and placebo groups (categories) over time (rows). Pairwise post-hoc contrasts were performed to assess the between and within group differences in outcome measures at each time point.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	The a priori threshold for statistical significance was p<0.05. The main effect analysis for plasma HIV RNA copy number/mL over time and between the 2 groups did not achieve p<0.05 (not statistically significant).
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Soluble TNFR2; Serum Biomarkers of Immune Activation
Description	serum soluble tumor necrosis factor receptor-2 concentration
Time Frame	Baseline, week 8, week 16

Outcome Measure Data

Analysis Population Description

sTNFR2

Arm/Group Title	Placebo	DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
Measure Participants	10	10
Baseline	2220 (389)	2436 (431)
week 8	2218 (411)	2617 (638)
week 16	2279 (415)	2388 (449)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DPPIV Inhibition
	Comments	The main effect analysis was applied to both rows (timepoint) and categories (groups). It used linear mixed models to simultaneously assess differences in serum TNFR2 levels between the DPP4 inhibitor and placebo groups (categories) over time (rows). Pairwise post-hoc contrasts were performed to assess the between and within group differences in outcome measures at each time point.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	The a priori threshold for statistical significance was p<0.05. The main effect analysis for serum TNFR2 levels over time and between the 2 groups did not achieve p<0.05 (not statistically significant).
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	SDF1α; Serum Biomarkers of Immune Activation
Description	serum stromal cell-derived factor-1α concentration
Time Frame	Baseline, week 8, week 16

Outcome Measure Data

Analysis Population Description

SDF1α

Arm/Group Title	Placebo	DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
Measure Participants	10	10
Baseline	2327 (304)	2378 (441)
week 8	2313 (364)	1208 (605)
week 16	2309 (400)	1277 (490)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DPPIV Inhibition
	Comments	The main effect analysis was applied to both rows (timepoint) and categories (groups). It used linear mixed models to simultaneously assess differences in serum SDF1α levels between the DPP4 inhibitor and placebo groups (categories) over time (rows). Pairwise post-hoc contrasts were performed to assess the between and within group differences in outcome measures at each time point.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0002
	Comments	The a priori threshold for statistical significance was p<0.05. The main effect analysis for SDF1-alpha levels over time and between the 2 groups achieved p<0.0002.
	Method	Mixed Models Analysis
	Comments

5. Secondary Outcome

Title	RANTES; Serum Biomarkers of Immune Activation
Description	serum Regulated on Activation, Normal T cell Expressed and Secreted concentration
Time Frame	Baseline, week 8, week 16

Outcome Measure Data

Analysis Population Description

RANTES

Arm/Group Title	Placebo	DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
Measure Participants	10	10
Baseline	80.8 (23.2)	64.4 (37.2)
week 8	85.3 (27.7)	68.5 (43.0)
week 16	74.9 (27.8)	62.8 (32.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DPPIV Inhibition
	Comments	The main effect analysis was applied to both rows (timepoint) and categories (groups). It used linear mixed models to simultaneously assess differences in serum RANTES levels between the DPP4 inhibitor and placebo groups (categories) over time (rows). Pairwise post-hoc contrasts were performed to assess the between and within group differences in outcome measures at each time point.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	The a priori threshold for statistical significance was p<0.05. The main effect analysis for serum RANTES levels over time and between the 2 groups did not achieve p<0.05 (not statistically significant).
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Oral Glucose Tolerance
Description	Area under the 75-gr oral glucose tolerance curve (AUCg) based on plasma glucose values measured at 0, 30, 60, 90, and 120 mins post-glucose challenge.
Time Frame	Baseline, week 8, week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
Measure Participants	10	10
Baseline AUCg	142.5 (26.6)	145.6 (32.5)
Week 8 AUCg	158.0 (26.7)	133.6 (24.6)
Week 16 AUCg	157.5 (23.2)	142.5 (21.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DPPIV Inhibition
	Comments	The main effect analysis was applied to both rows (timepoint) and categories (groups). It used linear mixed models to simultaneously assess differences in area under the glucose tolerance curves between the DPP4 inhibitor and placebo groups (categories) over time (rows). Pairwise post-hoc contrasts were performed to assess the between and within group differences in outcome measures at each time point.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.04
	Comments	The a priori threshold for statistical significance was p<0.05. The main effect analysis for area under the glucose tolerance curve over time and between the 2 groups achieved p<0.04.
	Method	Mixed Models Analysis
	Comments

7. Secondary Outcome

Title	Self-reported Symptoms
Description	Cumulative number of self-reported symptoms based on the Division of AIDS Grading Scale for the Severity of Adult Adverse Events (0-4 scale where 0 is no new symptoms, 4 is serious adverse event or toxicity)
Time Frame	Monthly for 4 months

Outcome Measure Data

Analysis Population Description

Cumulative frequency over 16 weeks of any self-reported symptoms on the DAIDS scale

Arm/Group Title	Placebo	DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months	Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
Measure Participants	10	10
Hypoglycemia symptoms	1	3
GI symptoms	8	3
Upper respiratory symptoms	10	5
Generalized fatigue	5	2
Headache	5	4
Other (e.g., rash, muscle pain, mood change)	6	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, DPPIV Inhibition
	Comments	Kruskal-Wallis non-parametric test of cell frequencies
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	The a priori threshold for statistical significance was p<0.05. The non-paramteric test for adverse event cummulative frequency between the 2 groups did not achieve p<0.05 (not statistically significant)
	Method	Kruskal-Wallis
	Comments

Adverse Events

Time Frame	16 weeks
Adverse Event Reporting Description	SAE or AE Any self reported symptom that was graded greater than 2 on the DAIDS severity scale during the 16 week period. These were reported as a serious or adverse event or toxicity. Other adverse event: Any self-reported symptom that was graded less than or equal to 2 (DAIDS scale) during the 16 week period;these are not serious adverse events.
Arm/Group Title	Placebo		DPPIV Inhibition
Arm/Group Description	Four months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Placebo : Daily placebo for 4 months		Four months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Sitagliptin : 100 mg sitagliptin daily for 4 months
All Cause Mortality
	Placebo		DPPIV Inhibition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		DPPIV Inhibition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		DPPIV Inhibition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/10 (70%)		6/10 (60%)
Gastrointestinal disorders
Gastrointestinal symptoms	5/10 (50%)	8	2/10 (20%)	3
General disorders
Generalized fatigue	3/10 (30%)	5	1/10 (10%)	2
Headache	4/10 (40%)	5	2/10 (20%)	4
Metabolism and nutrition disorders
Hypoglycemia symptoms	1/10 (10%)	1	2/10 (20%)	3
Musculoskeletal and connective tissue disorders
Muscle pain	1/10 (10%)	1	1/10 (10%)	1
Psychiatric disorders
Mood change	2/10 (20%)	3	2/10 (20%)	3
Respiratory, thoracic and mediastinal disorders
Upper respiratory symptoms	6/10 (60%)	10	3/10 (30%)	5
Skin and subcutaneous tissue disorders
Rash	1/10 (10%)	2	1/10 (10%)	1

Limitations/Caveats

Potential for type 2 error given small sample size. But, study was powered to detect significant decline in CD4 count. Measures of monocyte and lymphocyte activation should be conducted.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.