pioglitazone and HIV Coinfection studies

Pioglitazone: A thiazolidinedione and PPAR GAMMA agonist that is used in the treatment of TYPE 2 DIABETES MELLITUS.
pioglitazone : A member of the class of thiazolidenediones that is 1,3-thiazolidine-2,4-dione substituted by a benzyl group at position 5 which in turn is substituted by a 2-(5-ethylpyridin-2-yl)ethoxy group at position 4 of the phenyl ring. It exhibits hypoglycemic activity.

Research Excerpts

Excerpt	Relevance	Reference
" We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity."	9.15	Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. ( Bopp, C; Cade, WT; Hubert, S; Laciny, E; Lassa-Claxton, S; Mondy, KE; Overton, ET; Reeds, DN; Yarasheski, KE, 2011)
"Pioglitazone was well tolerated and no one discontinued due to side effects."	6.80	Pioglitazone for Hepatic Steatosis in HIV/Hepatitis C Virus Coinfection. ( Benator, D; Chairez, C; Hadigan, C; Kleiner, DE; Kovacs, JA; Matthews, L; McManus, M; Morse, CG; Nettles, MJ; Zemanick, K, 2015)
": Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment."	6.79	Pilot study of pioglitazone before HCV retreatment in HIV/HCV genotype 1-infected subjects with insulin resistance and previous nonresponse to peginterferon and ribavirin therapy: A5239. ( Alston-Smith, B; Andersen, J; Chung, RT; Glesby, MJ; Hadigan, C; Kitch, D; Luetkemeyer, A; Marks, KM; Tien, P, 2014)
" We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity."	5.15	Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. ( Bopp, C; Cade, WT; Hubert, S; Laciny, E; Lassa-Claxton, S; Mondy, KE; Overton, ET; Reeds, DN; Yarasheski, KE, 2011)
"Pioglitazone was well tolerated and no one discontinued due to side effects."	2.80	Pioglitazone for Hepatic Steatosis in HIV/Hepatitis C Virus Coinfection. ( Benator, D; Chairez, C; Hadigan, C; Kleiner, DE; Kovacs, JA; Matthews, L; McManus, M; Morse, CG; Nettles, MJ; Zemanick, K, 2015)
": Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment."	2.79	Pilot study of pioglitazone before HCV retreatment in HIV/HCV genotype 1-infected subjects with insulin resistance and previous nonresponse to peginterferon and ribavirin therapy: A5239. ( Alston-Smith, B; Andersen, J; Chung, RT; Glesby, MJ; Hadigan, C; Kitch, D; Luetkemeyer, A; Marks, KM; Tien, P, 2014)

Research

Studies (6)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Change in Hepatic Steatosis and Hepatic Inflammation/Fibrosis in HIV/HCV Co-infected Patients With Steatosis.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	2 (33.33)	29.6817
2010's	4 (66.67)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Omeragic, A	1
Kara-Yacoubian, N	1
Kelschenbach, J	1
Sahin, C	1
Cummins, CL	1
Volsky, DJ	1
Bendayan, R	1
Marks, KM	1
Kitch, D	1
Chung, RT	1
Hadigan, C	2
Andersen, J	1
Tien, P	1
Luetkemeyer, A	1
Alston-Smith, B	1
Glesby, MJ	1
Matthews, L	1
Kleiner, DE	1
Chairez, C	1
McManus, M	1
Nettles, MJ	1
Zemanick, K	1
Morse, CG	1
Benator, D	1
Kovacs, JA	1
Yarasheski, KE	1
Cade, WT	1
Overton, ET	1
Mondy, KE	1
Hubert, S	1
Laciny, E	1
Bopp, C	1
Lassa-Claxton, S	1
Reeds, DN	1
Calmy, A	1
Hirschel, B	1
Hans, D	1
Karsegard, VL	1
Meier, CA	1
Sheffield, CA	1
Kane, MP	1
Busch, RS	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Pioglitazone for Hepatic Steatosis in HIV/HCV Co-infection[NCT00742326]	Phase 4	13 participants (Actual)	Interventional	2008-08-31	Terminated (stopped due to Enrollment stopped prior to complete enrollment due to slow accrual)
Exercise and Pioglitazone for HIV-Metabolic Syndromes[NCT00639457]		44 participants (Actual)	Interventional	2005-01-31	Completed
Myocardial Function, Free Fatty Acid and Glucose Metabolism in HIV Metabolic Syndrome[NCT00656851]		24 participants (Actual)	Interventional	2005-09-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Change in hepatic steatosis and hepatic inflammation/fibrosis in HIV/HCV co-infected patients with steatosis. Change in Hepatic Fat Content measured by MR spectroscopy: 48 weeks compared to Baseline (NCT00742326)
Timeframe: 48 weeks

Change in Insulin Resistance in HIV- and HCV-infected Patients With Steatosis Compared to Placebo

Intervention	percentage of hepatic fat on MRS (Mean)
Pioglitazone	-7.43
Placebo	-2.17

Change in Glucose Area Under the Curve from standard oral glucose challenge ( baseline to 2 hours): Week 48 - Baseline values (NCT00742326)
Timeframe: 48 weeks

Abdominal Subcutaneous Fat Volume

Hematocrit

Intervention	mg*120 minutes/dL (Mean)
Pioglitazone	-31
Placebo	11

Intervention	cm3 (Mean)
	Baseline	Week 16
Pioglitazone	2101	2164
Pioglitazone + Exercise Training	1877	1905

Percentage of blood volume that is red cells (NCT00639457)
Timeframe: Baseline and Week 16

Hemoglobin

Hepatic Glucose Production Rate

Intervention	% red cells (Mean)
	Baseline Hematocrit	Week 16 Hematocrit
Pioglitazone	39.9	39.6
Pioglitazone + Exercise Training	40.7	39.7

Intervention	g/L (Mean)
	Baseline Hemoglobin	Week 16 Hemoglobin
Pioglitazone	13.8	13.7
Pioglitazone + Exercise Training	13.8	13.6

ability of insulin to suppress hepatic glucose production = hepatic insulin sensitivity (NCT00639457)
Timeframe: Baseline and week 16

Hepatic Lipid Content

Insulin-stimulated Glucose Disposal Rate

Intervention	percent suppression (Mean)
	Baseline	Week 16
Pioglitazone	32	40
Pioglitazone + Exercise Training	37	42

Intervention	percent of water (Mean)
	Baseline	Week 16
Pioglitazone	12.1	10.7
Pioglitazone + Exercise Training	8.0	5.5

Insulin-mediated glucose disposal rate per kg of fat free mass per min (NCT00639457)
Timeframe: Baseline and week16

Liver Enzyme Levels

Myocardial Contractility

Intervention	µmol glucose/kg FFM/min (Mean)
	Baseline	Week 16
Pioglitazone	30	37
Pioglitazone + Exercise Training	34	48

Intervention	U/L (Mean)
	Baseline ALT	Week 16 ALT	Baseline AST	Week 16 AST
Pioglitazone	38	39	34	30
Pioglitazone + Exercise Training	34	32	27	27

E/A ratio; ratio of the early (E) to late (A) ventricular filling velocities (NCT00639457)
Timeframe: Baseline and week 16

Myocardial Contractility-DBP

Intervention	ratio (Mean)
	Baseline E/A ratio	Week 16 E/A ratio
Pioglitazone	1.3	1.4
Pioglitazone + Exercise Training	1.2	1.4

Diastolic blood pressure; vascular pressure during ventricular relaxation (diastole) (NCT00639457)
Timeframe: Baseline and week 16

Myocardial Contractility-DT

Intervention	mmHg (Mean)
	Baseline DBP	Week 16 DBP
Pioglitazone	65	67
Pioglitazone + Exercise Training	68	61

Deceleration time; time from the peak of early diastolic filling to baseline (NCT00639457)
Timeframe: Baseline and week 16

Myocardial Contractility-LV Ejection Time

Intervention	msec (Mean)
	Baseline DT	Week 16 DT
Pioglitazone	204	193
Pioglitazone + Exercise Training	214	190

Time required to empty the left ventricle into the aorta (NCT00639457)
Timeframe: Baseline and week 16

Myocardial Contractility-SBP

Intervention	msec (Mean)
	Baseline LV ejection time	Week 16 LV ejection time
Pioglitazone	296	294
Pioglitazone + Exercise Training	281	305

Systolic blood pressure; peak vascular pressure during ventricular contraction (NCT00639457)
Timeframe: Baseline and week 16

Serum Adiponectin Levels

Serum Lipid and Lipoprotein Levels

Visceral Fat Volume

Fasting Glucose Insulin and HOMA

Intervention	mmHg (Mean)
	Baseline SBP	Week 16 SBP
Pioglitazone	114	114
Pioglitazone + Exercise Training	121	114

Intervention	µg/mL (Mean)
	Baseline serum adiponectin	Week 16 serum adiponectin
Pioglitazone	4.7	7.0
Pioglitazone + Exercise Training	4.8	6.5

Intervention	mM/L (Mean)
	Baseline Triglycerides	Week 16 Triglycerides	Baseline Total Cholesterol	Week 16 Total cholesterol	Baseline LDL cholesterol	Week 16 LDL cholesterol	Baseline HDL cholesterol	Week 16 HDL cholesterol
Pioglitazone	2.3	2.5	4.9	4.6	2.8	2.5	0.99	0.98
Pioglitazone + Exercise Training	2.1	1.8	4.7	4.5	2.7	2.6	1.06	1.09

Intervention	cm3 (Mean)
	Baseline	Week 16
Pioglitazone	1933	1970
Pioglitazone + Exercise Training	1890	1746

fasting plasma glucose, insulin concentrations and HOMA-insulin resistance (NCT00656851)
Timeframe: Week 0 and 16

Fasting Lipids and Lipoproteins

Intervention	mg/dL µU/mL (Mean)
	glucose (mg/dL) wk 0	glucose wk 16	insulin (µU/mL) wk 0	insulin wk 16	HOMA-IR wk 0	HOMA-IR wk 16
Exercise Training	91.9	86.8	14.8	11.8	3.3	2.6
Pioglitazone	102	95.3	20.5	11.4	6.1	2.8

fasting serum triglycerides, LDL-, and HDL-cholesterol concentrations (NCT00656851)
Timeframe: Week 0 and 16

Myocardial Contractile Function During Diastole

Intervention	mg/dL (Mean)
	triglycerides wk 0	triglycerides wk 16	LDL-cholesterol wk 0	LDL-cholesterol wk 16	HDL-cholesterol wk 0	HDL-cholesterol wk 16
Exercise Training	185	159	112	90	38.1	39.8
Pioglitazone	199	182	115	97	38.9	38.8

"Echocardiographic quantification of (E/A) early to late diastolic filling velocity. Aria transfer blood to the ventricles in 2 steps:~blood collected in the atria falls into the ventricles when the atrioventricular valves opens. In the left heart, the velocity at which the blood moves during this initial action is called the early or E filling velocity.~residual blood in the atria, is emptied during diastole by atrial contraction. The velocity of the blood during atrial contraction is the A (for atrial) filling velocity. These are expressed as a ratio (E/A). If A exceeds E velocity (ratio <1.0) this is a clinical marker of diastolic dysfunction. This can occur when the left ventricular wall becomes so stiff as to impair proper filling, which can lead to diastolic heart failure." (NCT00656851)
Timeframe: Weeks 0 and 16

Myocardial Contractile Function During Systole

Intervention	ratio (Mean)
	Week 0	Week 16
Exercise Training	1.4	1.5
Pioglitazone	1.4	1.4

Echocardiographic quantification of E' wall velocity during systole averaged at the lateral wall and septum (NCT00656851)
Timeframe: Weeks 0 and 16

Myocardial Fatty Acid Esterification

Intervention	cm/sec (Mean)
	Week 0	Week 16
Exercise Training	13.1	13.6
Pioglitazone	12.7	12.8

Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid esterification as a % of total fatty acid extraction (NCT00656851)
Timeframe: Weeks 0 and 16

Myocardial Fatty Acid Oxidation Rate

Intervention	(% of total fatty acid extraction) (Mean)
	Week 0	Week 16
Exercise Training	4	7
Pioglitazone	7	4

Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid oxidation rate. (NCT00656851)
Timeframe: Weeks 0 and 16

Myocardial Fatty Acid Utilization Rate

Intervention	(nmol palmitate/g heart muscle/min (Mean)
	Week 0	Week 16
Exercise Training	106.3	97.5
Pioglitazone	92.4	110.1

Radio-tracer (11C-palmitate) and positron emission tomography quantification of myocardial fatty acid utilization rate. The rate at which palmitate exits the blood, enters the muscle cells in the left ventricle, and is metabolized (oxidation, re-esterification). (NCT00656851)
Timeframe: Weeks 0 and 16

Myocardial Glucose Utilization Rate

Intervention	(nmol palmitate/g heart muscle/min (Mean)
	Week 0	Week 16
Exercise Training	119.8	130.4
Pioglitazone	119.3	129.3

Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate. The rate at which glucose exits the blood, enters the muscle cells in the left ventricle, and is metabolized (ATP generation, glycolysis, glycogenolysis, or lactate production). Total glucose utilization rate in the left ventricle of the heart. (NCT00656851)
Timeframe: Weeks 0 and 16

Myocardial Glucose Utilization Rate Per Unit Insulin

Intervention	(nmol glucose/g heart muscle/min (Mean)
	Week 0	Week 16
Exercise Training	106.7	87.2
Pioglitazone	109.6	109.1

Radio-tracer (11C-glucose) and positron emission tomography quantification of myocardial glucose utilization rate per unit of plasma insulin. Total glucose utilization rate in the left ventricle of the heart expressed per unit of the circulating plasma insulin concentration. (NCT00656851)
Timeframe: Weeks 0 and 16

Article	Year
Pilot study of pioglitazone before HCV retreatment in HIV/HCV genotype 1-infected subjects with insulin resistance and previous nonresponse to peginterferon and ribavirin therapy: A5239. Journal of acquired immune deficiency syndromes (1999), 2014, Mar-01, Volume: 65, Issue:3 Topics: Adult; Alanine Transaminase; Antiviral Agents; Aspartate Aminotransferases; Female; Genotype; Hepaci	2014
Pioglitazone for Hepatic Steatosis in HIV/Hepatitis C Virus Coinfection. AIDS research and human retroviruses, 2015, Volume: 31, Issue:10 Topics: Adult; Coinfection; Double-Blind Method; Fatty Liver; Female; Hepatitis C, Chronic; Histocytochemist	2015
Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. American journal of physiology. Endocrinology and metabolism, 2011, Volume: 300, Issue:1 Topics: Adiposity; Adolescent; Adult; Combined Modality Therapy; Diabetes Mellitus, Type 2; Exercise; Female	2011
Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. American journal of physiology. Endocrinology and metabolism, 2011, Volume: 300, Issue:1 Topics: Adiposity; Adolescent; Adult; Combined Modality Therapy; Diabetes Mellitus, Type 2; Exercise; Female	2011
Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. American journal of physiology. Endocrinology and metabolism, 2011, Volume: 300, Issue:1 Topics: Adiposity; Adolescent; Adult; Combined Modality Therapy; Diabetes Mellitus, Type 2; Exercise; Female	2011
Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. American journal of physiology. Endocrinology and metabolism, 2011, Volume: 300, Issue:1 Topics: Adiposity; Adolescent; Adult; Combined Modality Therapy; Diabetes Mellitus, Type 2; Exercise; Female	2011
Glitazones in lipodystrophy syndrome induced by highly active antiretroviral therapy. AIDS (London, England), 2003, Mar-28, Volume: 17, Issue:5 Topics: Adult; Anthropometry; Antiretroviral Therapy, Highly Active; Female; Follow-Up Studies; HIV Infectio	2003

Article	Year
Peroxisome Proliferator-Activated Receptor-gamma agonists exhibit anti-inflammatory and antiviral effects in an EcoHIV mouse model. Scientific reports, 2019, 07-01, Volume: 9, Issue:1 Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Brain; Cells, Cultured; Disease Models, Animal;	2019
Off-label use of exenatide for the management of insulin-resistant type 1 diabetes mellitus in an obese patient with human immunodeficiency virus infection. Pharmacotherapy, 2007, Volume: 27, Issue:10 Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Exenatide; HIV Infections; Humans; Hypo	2007

pioglitazone and HIV Coinfection