Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation

Figures & data

Table 1 Baseline characteristics of study participants with data on at least one biomarker (Total N = 63)

Category	Variable	Variable Subcategory	rhGH/Rosiglitazone (n = 20)	Rosiglitazone (n = 15)	rhGH (n = 13)	Double Placebo (n = 15)
Demographic	Age, years		46.0 (41.5,52.0)	47.0 (45.0,52.0)	49.0 (47.0,51.0)	48.0 (42.0,55.0)
	Sex	Male	17 (85.0%)	13 (86.7%)	10 (76.9%)	11 (73.3%)
	Race	White	14 (70.0%)	11 (73.3%)	8 (61.5%)	10 (66.7%)
		Black	5 (25.0%)	4 (26.7%)	5 (38.5%)	6 (33.3%)
		>1 race	1 (5.0%)	0	0	0
	Ethnicity	Hispanic	7 (35.0%)	8 (53.3%)	2 (15.4%)	7 (46.7%)
		Non-Hispanic	13 (65.0%)	7 (46.7%)	11 (84.6%)	8 (53.3%)
HIV	Antiretroviral regimen	≥2 NRTIs + NNRTI	6 (30.0%)	6 (40.0%)	6 (46.1%)	7 (46.7%)
		≥2 NRTIs + PI	10 (50.0%)	7 (46.7%)	5 (38.5%)	7 (46.7%)
		≥3 NRTIs	2 (10.0%)	0	1 (7.7%)	0
		Other	2 (10.0%)	2 (13.3%)	1 (7.7%)	1 (6.7%)
		Stavudine or zidovudine use	5 (25.5%)	5 (33.3%)	4 (30.8%)	5 (33.3%)
Concomitant Medications	Fibrate		3 (15.0%)	2 (13.3%)	2 (15.4%)	3 (20.0%)
	Statin		7 (35.0%)	7 (46.7%)	4 (30.8%)	3 (20.0%)
	Fish oil		0	1 (6.7%)	0	1 (6.7%)
	Antihypertensive		6 (30.0%)	5 (33.3%)	4 (30.1%)	5 (33.3%)
Anthropometric	Height, cm		171.5 (166.5,176.5)	173.2 (167.0,177.4)	173.8 (167.7,179.6)	172.1 (165.9,175.4)
	Weight, kg		85.1 (75.3,94.1)	76.7 (71.4,83.0)	88.5 (82.1,99.2)	79.4 (71.3,98.8)
	Body mass index, kg/m^2		29.4 (25.3,31.5)	26.2 (25.0,28.5)	29.6 (28.9,32.0)	28.1 (25.5,33.9)
	Waist circumference, cm		101.4 (97.0,108.0)	98.2 (95.2,102.7)	106.2 (103.3,108.8)	99.8 (94.2,113.4)
	Hip circumference, cm		97.8 (95.8,100.0)	95.0 (92.9,97.2)	101.5 (99.2,106.9)	96.7 (92.3,109.3)
	Waist:hip ratio		1.0 (1.0,1.1)	1.0 (1.0,1.1)	1.0 (1.0,1.1)	1.0 (1.0,1.1)
Laboratory Values	Fasting insulin, miU/mL		18.1 (15.2,23.4)	18.9 (12.2,25.0)	17.1 (12.2,23.8)	16.0 (11.9,17.6)
	Fasting glucose, mg/dL		90.5 (83.5,96.5)	89.0 (81.0,92.0)	94.0 (90.0,104.0)	95.0 (89.0,98.0)
	QUICKI		0.31 (0.30,0.32)	0.31 (0.30,0.33)	0.31 (0.29,0.33)	0.32 (0.30,0.33)
	CD4 count*, cells x 10^6/L		556.0 (378.0,755.0)	737.0 (458.0,792.0)	495.0 (312.0,682.0)	604.0 (282.0,718.0)
	HIV RNA < 400** copies/ml		15 (75.0%)	11 (78.6%)	9 (69.2%)	6 (46.2%)
	VAT, L		4.4 (2.7,7.3)	4.8 (4.2,5.6)	4.4 (3.6,6.4)	4.9 (3.8,7.4)
	SAT, L		21.9 (14.2,32.1)	18.3 (15.9,21.7)	24.7 (16.5,33.5)	21.0 (17.1,33.9)
	SI, μU * 10^−4 * min^−1 * ml^−1		1.7 (1.1,2.4)	1.9 (1.4,2.7)	1.7 (1.1,2.9)	1.6 (1.5,2.9)
	Insulin AUC, pmol/L*2 h		405.0 (314.0,749.0)	324.4 (200.4,651.2)	609.1 (225.4,708.7)	327.9 (239.8,872.2)
	Glucose AUC, mmol/L*2 h		517.0 (476.8,590.3)	525.3 (389.4,674.1)	518.0 (486.5,664.4)	527.1 (493.3,556.3)

Continuous variables are expressed as median (IQR).

Abbreviations: AUC, area under the curve from 2 h oral glucose tolerance test; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; QUICKI, quantitative insulin sensitivity check index; SAT, subcutaneous adipose tolerance tissue volume; SI, insulin sensitivity by frequently sampled intravenous glucose tolerance test; VAT, visceral adipose tissue volume.

* CD4 count available on n = 18, 13, 11, and 11 in rhGH/rosiglitazone, rosiglitazone, rhGH, and double placebo arms, respectively.

** HIV RNA data available on n = 20, 14, 13, and 13 in rhGH/rosiglitazone, rosiglitazone, rhGH, and double placebo arms, respectively.

Table 2 Changes in Biomarkers by Study Arm

	Rosiglitazone + rhGH n = 20			Rosiglitazone n = 15			rhGH n = 13			Double Placebo n = 15			p-value*
Biomarker	Baseline	12-week	12-wk change	Baseline	12-week	12-wk change	Baseline	12-week	12-wk change	Baseline	12-week	12-wk change
Adiponectin, ng/ml	n = 14	n = 14	n = 14	n = 12	n = 12	n = 12	n = 9	n = 9	n = 9	n = 12	n = 12	n = 12
	5.2 (3.5,6.6)	10.4 (7.7,14.2)	4.7** (1.5,6.7)	8.2 (5.8,11.8)	15.2 (10.0,27.5)	5.7** (2.6,19.9)	7.6(4.9,8.7)	7.0 (5.7,9.9)	−0.1 (−1.5,1.2)	7.2 (4.9,11.6)	6.5 (4.6,9.9)	−0.5 (−1.0,0.2)	0.0004
hsCRP, mg/ml	n = 14	n = 14	n = 14	n = 12	n = 12	n = 12	n = 9	n = 9	n = 9	n = 12	n = 12	n = 12
	2.33 (0.7,4.6)	0.52 (0.2,1.5)	−1.42 (−2.1,−0.5)	3.09 (0.9,8.0)	1.03 (0.5,2.8)	−1.18 (−4.8,−0.4)	1.76 (0.6,7.9)	0.69 (0.2,1.3)	−1.53 (−4.5,−0.2)	3.36 (0.7,7.4)	0.92 (0.4,3.9)	−0.37 (−2.9,−0.1)	0.74
Homocysteine, µmol/ml	n = 14	n = 14	n = 14	n = 12	n = 12	n = 12	n = 9	n = 9	n = 9	n = 12	n = 12	n = 12
	10.5 (8.8,11.8)	11.7 (9.7,13.4)	1.3 (−0.4,2.1)	11.5 (9.1,14.3)	10.2 (9.1,12.6)	−0.6 (−3.3,0.2)	11.5 (10.0,13.4)	10.8 (10.1,11.6)	−0.9 (−1.1,0.8)	10.9 (8.1,13.5)	9.8 (8.5,12.8)	−0.2 (−1.6,2.5)	0.15
IL-1-β, pg/ml	n = 14	n = 14	n = 14	n = 12	n = 12	n = 12	n = 9	n = 9	n = 9	n = 12	n = 12	n = 12
	0.6 (0.3,1.5)	0.5 (0.3,1.2)	0 (−0.6,0.0)	0.3 (0.3,0.9)	0.3 (0.3,1.0)	0 (−0.4,0.5)	0.8 (0.3,0.9)	0.8 (0.3,1.0)	0 (0.0,0.7)	0.3 (0.3,1.1)	0.3 (0.3,1.0)	0 (−0.2,0.3)	0.54
IL-6, pg/ml	n = 14	n = 14	n = 14	n = 12	n = 12	n = 12	n = 9	n = 9	n = 9	n = 12	n = 12	n = 12
	1.1 (0.8,1.7)	0.9 (0.7,1.5)	−0.1 (−0.3,0.4)	1.2 (0.8,2.5)	0.9 (0.7,1.4)	−0.03(−1.0,0.2)	1.3 (1.0,1.8)	0.9 (0.6,1.7)	−0.3 (−0.4,−0.2)	0.9(0.8,1.5)	1.0 (0.6,1.3)	−0.1(−0.2,0.1)	0.43
TNFα, pg/ml	n = 14	n = 14	n = 14	n = 12	n = 12	n = 12	n = 9	n = 9	n = 9	n = 12	n = 12	n = 12
	7.4 (6.2,10.1)	8.0 (6.2,9.9)	0.6 (−0.7,1.2)	6.8 (5.3,9.6)	5.6 (5.3,7.0)	−0.7(−2.6,−0.2)	7.1(6.7,8.5)	6.5 (4.5,7.1)	−1.2(−2.0,−0.5)	7.5(5.9,8.3)	7.7 (4.5,8.5)	−0.5(−0.8,1.0)	0.26
IFNγ, pg/ml	n = 14	n = 14	n = 14	n = 12	n = 12	n = 12	n = 9	n = 9	n = 9	n = 12	n = 12	n = 12
	2.5 (1.6,4.3)	3.5 (3.0,4.2)	0.7 (−0.1,1.4)	3.7 (2.2,7.4)	3.5 (2.0,6.4)	−0.5 (−2.2,0.9)	3.3(2.5,5.4)	3.1 (2.7,3.7)	0.5 (−2.7,0.6)	3.9 (1.8,5.9)	3.6 (1.8,5.7)	0.1 (−1.5,2.0)	0.62
Fibrinogen, mg/dL	n = 15	n = 15	n = 15	n = 10	n = 10	n = 10	n = 11	n = 11	n = 11	n = 12	n = 12	n = 12
	182.0 (146,236)	197.0 (156,222)	−4 (−34,38)	229.0 (168,271)	206.0 (154,226)	−20.5(−87,−2)	193.0 (184,300)	223.0 (188,268)	−1 (−25,30)	237.0 (176,285)	210.5 (166.5,249.5)	−10.5 (−36.5,3.5)	0.40
PAI-1 antigen, ng/ml	n = 15	n = 15	n = 15	n = 8	n = 8	n = 8	n = 10	n = 10	n = 10	n = 13	n = 13	n = 13
	393.2 (72.9, 480.4)	240.4 (76.6, 474.0)	10.2 (−197.2, 433.5)	611.9 (254.7, 890.2)	434.4 (223.8, 943.9)	−134.1 (−460.8, 306.7)	412.6 (373.4, 598.2)	546.2 (301.2, 822.2)	38.5 (−14.1, 249.2)	320.8 (131.4, 582.2)	477.3 (304.8, 581.4)	−4.1 (−53.4, 73.0)	0.56
tPA antigen, ng/ml	n = 15	n = 15	n = 15	n = 8	n = 8	n = 8	n = 10	n = 10	n = 10	n = 13	n = 13	n = 13
	9.0 (6.2,11.7)	5.6 (4.4,8.2)	−3.5 (−5.6,-1.3)	9.0 (7.6,14.3)	7.7 (5.5,13.5)	−1.1 (−3.7,−0.1)	11.4 (9.3,11.8)	10.1 (7.3,11.5)	−2.1 (−2.2,−0.3)	13.2 (10.8,14.0)	11.7 (7.6,14.8)	0.5 (−3.0,1.2)	0.10

Note: Data are presented as median (interquartile range).

* Kruskal–Wallis test.

** p = 0.0011 for rosiglitazone + rhGH compared to double placebo group, p = 0.0005 for rosiglitazone alone compared to double placebo group after Dunnett-Hsu multiple adjustments.

Figure 1 (a) Change in Adiponectin by Study Arm. p = 0.0004 across treatment arms by Kruskal–Wallis test. Within arm changes: rhGH/rosiglitazone p = 0.0010; rosiglitazone p = 0.0073; rhGH p = 0.82; double placebo p = 0.27. Boxplots display the median (line inside box), first and third quartiles (lower and upper edges of box), mean (diamond), and whiskers (maximum and minimum observations aside from outliers). Open circles depict the individual data points. (b) Change in C-reactive Protein by Study Arm. p = 0.74 across treatment arms by Kruskal–Wallis test. Within arm changes: rhGH/rosiglitazone p = 0.0001; rosiglitazone p = 0.012; rhGH p = 0.0078; double placebo p = 0.014.