Vitamin D insufficiency is associated with subclinical atherosclerosis in HIV-1-infected patients on combination antiretroviral therapy

Figures & data

Table 1. Patient characteristics according to presence of subclinical atherosclerosis.

	Total (N = 188)	Patients with subclinical atherosclerosis (N = 105)	Patients without subclinical atherosclerosis (N = 83)	p value
Males, no. (%)	162 (86.2)	92 (87.6)	70 (84.4)	0.441
White subjects, no. (%)	174 (92.5)	99 (94.3)	75 (90.4)	0.682
Age (years), mean (±SD)	49.1 (±5.4)	52.5 (±6.6)	45.2 (±4.9)	0.034
HIV transmission risk category, no. (%):
IDU	41 (21.8)	24 (22.9)	17 (20.5)	0.821
MSM	87 (46.3)	47 (44.8)	40 (48.2)	0.188
heterosexual	60 (31.9)	34 (32.4)	26 (31.3)	0.587
Vitamin D concentration (ng/mL), mean (±SD)	35.2 (±18.4)	18.2 (±10.5)	41.3 (±16.2)	<0.001
Patients with vitamin D insufficiency, no. (%)	84 (44.6)	57 (54.3)	27 (32.5)	0.019
Patients with vitamin D deficiency, no. (%)	29 (15.4)	19 (18.1)	10 (12)	0.042
Nadir CD4+ lymphocyte count (cells/mm^3), mean (±SD)	238 (±116)	175 (±79)	281 (±139)	0.028
Current CD4+ lymphocyte count (cells/mm^3), mean (±SD)	567 (±238)	542 (±224)	589 (±265)	0.079
Duration of HIV infection (years), mean (±SD)	13.4 (±8.3)	17.2 (±9.1)	9.3 (±4.7)	0.006
Patients with HIV RNA < 20 copies/mL, no. (%)	176 (93.6)	99 (94.3)	77 (92.7)	0.519
Patients with AIDS diagnosis, no. (%)	16 (8.5)	10 (9.5)	6 (7.2)	0.139
BMI (kg/m^2), mean (±SD)	25.9 (±3.1)	27.6 (±3.5)	24.1 (±3.1)	0.003
Waist circumference (cm), mean (±SD)	91.4 (±13.4)	93.5 (±13.9)	88.7 (±12.8)	0.066
Current smoking, no. (%)	96 (51.1)	69 (65.7)	27 (32.5)	0.025
Patients with chronic HCV infection, no. (%)	19 (10.1)	11 (10.5)	8 (9.6)	0.771
Patients with chronic HBV infection, no. (%)	10 (5.3)	4 (3.1)	6 (7.2)	0.192
Patients with arterial hypertension, no. (%)	55 (29.2)	36 (34.3)	19 (22.9)	0.047
Patients with metabolic syndrome, no. (%)	52 (27.7)	36 (34.3)	16 (19.3)	0.027
Calcium (mg/dL), mean (±SD)	9.3 (±2.2)	9.3 (±1.9)	9.2 (±1.7)	0.448
Phosphorus (mg/dL), mean (±SD)	3 (±1.4)	2.9 (±1.2)	3.1 (±1.5)	0.378
PTH (pg/mL), mean (±SD)	47.6 (±19.8)	48.2 (±20.7)	46.3 (±19.2)	0.351
Glucose (mg/dL), mean (±SD)	88.6 (±17.9)	90.4 (±15.2)	86.3 (±16.7)	0.107
Total cholesterol (mg/dL), mean (±SD)	204 (±56)	221 (±68)	187 (±45)	0.034
HDL cholesterol (mg/dL), mean (±SD)	46 (±19)	43 (±18)	48 (±20)	0.185
LDL cholesterol (mg/dL), mean (±SD)	146 (±27)	168 (±35)	124 (±21)	<0.001
Triglycerides (mg/dL), mean (±SD)	213 (±86)	225 (±89)	206 (±75)	0.087
eGFR (mL/min/1.73 m^2), mean (±SD)	82.6 (±18.7)	80.4 (±17.9)	84.3 (±18.3)	0.387

SD, standard deviation; IDU, injection drug users; MSM, men who have sex with men; AIDS, acquired immune deficiency syndrome; BMI, body mass index; HCV, hepatitis C virus; HBV, hepatitis B virus; PTH, parathyroid hormone; HDL, high-density lipoprotein; LDL, low-density lipoprotein; eGFR, estimated glomerular filtration rate (calculated by the CKD-EPI formula).¹²

Table 2. Current antiretroviral therapies and past exposure to antiretroviral drugs of the study cohort.

	Total (N = 188)	Patients with subclinical atherosclerosis (N = 105)	Patients without subclinical atherosclerosis (N = 83)	p value
Cumulative exposure to ART (years), mean (±SD)	11.7 (±3.9)	13.4 (±4.8)	10.1 (±3.6)	0.287
Current ART:
TDF/FTC, no. (%)	75 (39.9)	41 (39)	34 (41)	0.604
TAF/FTC, no. (%)	41 (21.8)	19 (18.1)	22 (26.5)	0.186
ABC/3TC, no. (%)	63 (33.5)	39 (37.1)	24 (28.9)	0.125
Nevirapine, no. (%)	16 (8.5)	11 (10.5)	5 (6)	0.448
TDF/FTC/efavirenz, no. (%)	12 (6.4)	8 (7.6)	4 (4.8)	0.381
TDF/FTC/rilpivirine or TAF/FTC/rilpivirine, no. (%)	39 (20.7)	25 (23.8)	14 (16.9)	0.197
Darunavir/r or darunavir/c, no. (%)	26 (13.8)	15 (14.3)	11 (13.2)	0.275
Atazanavir/r or atazanavir/c, no. (%)	12 (6.4)	4 (3.8)	8 (9.6)	0.119
Raltegravir, no. (%)	36 (19.1)	19 (18.1)	17 (20.5)	0.472
Dolutegravir, no. (%)	28 (14.9)	14 (13.3)	14 (16.9)	0.701
TDF/FTC/elvitegravir/c or TAF/FTC/elvitegravir/c, no. (%)	14 (7.5)	6 (5.7)	8 (9.6)	0.488
ABC/3TC/dolutegravir, no. (%)	21 (11.2)	12 (11.4)	9 (10.8)	0.664
TDF/FTC + raltegravir, no. (%)	25	15 (14.3)	10 (13.2)	0.318
3TC + PI, no. (%)	28 (14.9)	19 (18,1)	9 (10.8)	0.087
3TC + dolutegravir, no. (%)	4 (2.1)	3 (2.8)	1 (1.2)	0.885
Cumulative exposure (years), mean (±SD):
NNRTIs	6.6 (±2.6)	5.5 (±2.4)	7.2 (±2.8)	0.064
Pis	6.1 (±2.5)	7.8 (±3.2)	4.6 (±2.8)	0.032
INSTIs	3.5 (±1.9)	3.1 (±1.4)	3.9 (±1.7)	0.219

ART, antiretroviral therapy; SD, standard deviation; TDF/FTC, tenofovir disoproxil fumarate/emtricitabine; TAF/FTC, tenofovir alafenamide/emtricitabine; ABC/3TC, abacavir/lamivudine; elvitegravir/c, elvitegravir/cobicistat; 3TC, lamivudine; PI, ritonavir-boosted or cobicistat-boosted protease inhibitor; NNRTIs, non-nucleoside reverse transcriptase inhibitors; INSTIs, integrase strand transfer inhibitors.

Table 3. Mean values of carotid intima-media thickness of the 188 enrolled patients.

	IMT (mm), mean (±SD)
Right common carotid artery	0.86 (±0.38)
Left common carotid artery	0.84 (±0.35)
Right carotid bifurcation	0.88 (±0.39)
Left carotid bifurcation	0.87 (±0.41)
Right internal carotid artery	0.85 (±0.46)
Left internal carotid artery	0.83 (±0.44)

IMT, intima-media thickness; SD, standard deviation.

Table 4. Analysis by univariate and multivariate logistic regression of factors associated with subclinical atherosclerosis in the study cohort.

	Univariate analysis		Multivariate analysis
Factors	O.R. (95% C.I.)	p value	O.R. (95% C.I.)	p value
Vitamin D insufficiency	2.55 (1.76–3.38)	0.019	2.09 (1.61–2.53)	0.024
Vitamin D deficiency	1.97 (1.33–2.92)	0.042	1.69 (1.14–2.35)	0.048
Age >50 years	1.96 (1.49–2.41)	0.023	1.63 (1.25–1.92)	0.039
Current smoking	2.17 (1.67–2.62)	0.025	1.88 (1.44–2.29)	0.036
Hypertension	1.68 (1.28–2.06)	0.047	1.76 (1.34–2.28)	0.035
BMI >25 kg/m^2	4.11 (2.94–5.23)	<0.001	2.76 (1.89–3.65)	<0.001
Waist circumference >90 cm	1.54 (1.19–1.96)	0.033	1.39 (0.82–1.78)	0.067
Metabolic syndrome	2.55 (1.91–3.14)	0.027	2.29 (1.84–2.96)	0.031
Duration of HIV infection >10 years	1.88 (1.37–2.46)	0.018	1.55 (1.09–2.12)	0.044
Current CD4 lymphocyte count >500 cells/mm^3	1.66 (1.13–2.19)	0.037	1.42 (0.83–1.94)	0.103
Nadir CD4 lymphocyte count <200 cells/mm^3	1.99 (1.55–2.47)	<0.001	1.73 (1.28–2.39)	0.008
Total cholesterol >200 mg/dL	1.59 (1.14–1.97)	0.041	1.38 (0.83–1.69)	0.109
LDL cholesterol >150 mg/dL	1.94 (1.39–2.51)	0.008	1.68 (1.17–2.28)	0.037
Triglycerides >150 mg/dL	2.86 (1.78–3.95)	<0.001	2.41 (1.52–3.77)	0.009
Exposure to NNRTIs >5 years	0.73 (0.34–1.09)	0.068	0.94 (0.49–1.47)	0.187
Exposure to PIs >5 years	1.89 (1.44–2.47)	0.017	1.64 (1.19–2.13)	0.028

O.R., odds ratio; C.I., confidence interval; BMI, body mass index; LDL, low-density lipoprotein; NNRTIs, non-nucleoside reverse transcriptase inhibitors; PIs, ritonavir-boosted or cobicistat-boosted protease inhibitors..

Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367(1):20–29.

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Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.