Metabolic Syndrome in French HIV-Infected Patients: Prevalence and Predictive Factors After 3 Years of Antiretroviral Therapy

Abstract

Treatment of HIV infection with highly active antiretroviral therapy can induce metabolic complications and increase the risk of developing the metabolic syndrome (MS). The purpose of this study was to report the prevalence and the risk factors for MS in HIV-infected patients who started highly active antiretroviral therapy (HAART) after 2000. SYMET is a prospective, multicentric, cohort study evaluating the prevalence of MS in 269 patients who had received continuous HAART for 1 to 4 years up to September 2007. MS was defined according to the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) 2005 criteria. Cross-sectional assessment included clinical examination and fasting evaluation of metabolic, inflammatory, and oxidative parameters. Data were analyzed with Chi-square, Student, or Wilcoxon tests. Univariate and multivariate logistic regressions were performed to identify predictive factors for MS. The prevalence of MS was 18.2% after a median duration of HAART of 29.8 months. In multivariate analysis, predictive factors of MS were high non-HDL-cholesterol (OR=1.87; p<0.0001), high-sensitivity C-reactive protein levels (hsCRP) (OR=1.56; p=0.01), coinfection with hepatitis C virus (HCV) (OR=5.67; p=0.02), as well as age (OR=1.04; p=0.02) and duration of exposure to protease inhibitors (PI) (OR=1.03; p=0.02) or to abacavir (ABC) (OR=1.03; p=0.02). In this cohort of patients exposed to less than 4 years of HAART, MS prevalence was 18.2%. Older age, high hsCRP, HCV coinfection, and elevated non-HDL-cholesterol were risk factors for the MS. There was also a moderate significant association of increased risk of MS with cumulative PI and ABC exposure.

Introduction

M etabolic syndrome (MS) was described initially in the diabetic population. It is defined by the association of arterial hypertension, visceral obesity, hypertriglyceridemia, reduction of high-density lipoprotein (HDL)-cholesterol, and insulin resistance.¹ Simple evaluations of blood pressure, biological assessment (triglycerides, HDL-cholesterol, glucose), and waist measurement are sufficient to make this diagnosis. Thus, the presence of MS for a patient reflects the risk of progression toward insulin resistance, type 2 diabetes,² or cardiovascular disease.³ About 11% of the subjects with insulin resistance are likely to develop diabetes in the following 7 years. This percentage is around 32% when insulin resistance is associated with a deficit of insulin secretion.⁴ Once diabetes and its complications are present, the risk of developing cardiovascular disease increases by a factor of two to three.

Since the introduction of highly active antiretroviral treatment (HAART) for the treatment of HIV infection in 1996, the life expectancy of patients considerably increased, with a concomitant reduction in risk for opportunistic infections.⁵ In parallel, metabolic complications and abnormal fat distribution (dyslipidemia, insulin resistance, and lipodystrophy) were frequently observed after a few years of combination antiretroviral therapy.^6,7 Many of these morphologic and metabolic changes correspond to MS criteria, according to the National Education Program Treatment Panel III (NCEP-ATP III) definition. Thus, these metabolic complications associated with the increased lifespan of HIV patients on HAART naturally raise the question of a higher risk for cardiovascular morbidity.⁸ More effective clinical management and prevention of cardiovascular disease justify identification of MS in HIV-infected patients.⁹ Indeed, in 2005 cardiovascular disease represented the fourth leading cause of mortality among HIV patients in France, following HIV-related events, cancer, and hepatitis C.¹⁰

There has been a lot of discussion on the factors causing MS in HIV-infected patients. These metabolic alterations in HIV patients receiving HAART were initially described as side effects due primarily to specific antiviral treatments, in particular the protease inhibitors (PIs).⁶ The specific role of each antiretroviral drug class in the development of these metabolic abnormalities and cardiovascular risk is still a subject of debate, with studies suggesting the possible role of some nucleoside reverse transcriptor inhibitors (NRTIs) and PIs.^11,12

Recent studies suggest that other factors play an important role in the occurrence of these metabolic disturbances. Among those, production of proinflammatory cytokines, leading to insulin resistance and hypertriglyceridemia, is well recognized.¹³ A chronic inflammatory state is frequent in HIV infection, even if successfully treated. Thus, HIV infection by itself could be an additional risk factor in the pathophysiological process of metabolic syndrome development.¹⁴

In this context, we present a national, clinical, prospective, multicentric, and cross-sectional study (SYMET), whose objective was to define the prevalence of MS among HIV patients treated by HAART. This study also assessed the risk factors associated with MS in order to improve guidance for follow-up and management.

Materials and Methods

Two hundred and sixty-nine HIV patients receiving HAART were included in SYMET. This cohort of 269 HIV-infected adults was recruited in five French health care centers (University Hospitals of Nantes, Paris-Bichat, Dijon, and Departmental Hospitals of Roche sur Yon and Orléans) from January 2000 to September 2007.

Patients were included if they were 18 years old or more, if they had initiated HAART after January 1, 2000, and were receiving HAART for 1 to 4 years without reported therapeutic interruption. All the patients included signed a consent form, in accordance with the bioethics laws. Patients not adhering to these criteria, patients presenting signs of an active opportunistic infection, and pregnant women were excluded.

Patients were included in the study during a regular clinic visit. A clinical and biological assessment was carried out in order to be able to establish the MS diagnosis for each patient, according to new criteria defined in 2005 by the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI).¹⁵ Additional clinical information was collected in parallel, in order to study associated factors of comorbidity: history of HIV infection and therapeutic treatment from diagnosis to inclusion in the study, history or current infection by the hepatitis C virus (HCV) or hepatitis B virus (HBV), history of cardiovascular disease, cardiovascular risk factors [obesity, arterial hypertension (HT), type 2 diabetes, dyslipidemia, smoking, exercise], and family history of cardiovascular risk factors (HT, diabetes, dyslipidemia) or disease. Alcohol consumption was assessed asking for frequency of consumption, either occasional or regular. Physical activity was classified into three categories: none, low (<2 h/week, not every week), and high (>2 h/week with regular practice).

A full antiretroviral treatment history was recorded from patient's notes, with date of initiation and, if applicable, of interruption of each antiretroviral drug. Duration of exposure to each drug and each class of antiretrovirals was assessed. Patient's dietary habits were not recorded.

A complete clinical examination evaluated systolic and diastolic blood pressure determined using a sphygmomanometer after 10 min of rest in a sitting position, weight, size, and anthropometric parameter measures (waist and hip circumferences). Blood pressure and anthropometric assessments were recorded once, and were not subject to external quality control. Biological assessment was carried out, at fasting, to measure various parameters: glucose, total cholesterol, HDL-cholesterol, and triglycerides (HITACHI 917, Rock Systems Diagnosis, Basel, Switzerland). Low-density lipoprotein (LDL)-cholesterol was calculated by the Friedenwald formula and non-HDL-cholesterol by the subtraction of HDL-cholesterol from total cholesterol. Insulin was measured by a radioimmunological technique using the radioactivity Cobra Quantum counter (Perkin Elmer, Paris, France). Concentrations of Apo A1 and Apo B were measured by nephelemetry (Behring Nephelemeter Analyser II, Dade Behring, Rueil-Malmaison, France). HIV RNA viral load was measured by real time PCR (Amplicor Roche, Basel, Switzerland) and CD4 lymphocyte cell count by flow cytometry (Becton-Dickinson, Madrid, Spain) at inclusion. The inflammatory assessment included evaluation of high-sensitivity C-reactive protein (hsCRP) by nephelemetry (Behring Nephelemeter Analyser II, Dade Behring, Rueil Malmaison, France), interleukin 6 (IL-6) (Hight sensitivity Quantikine Human IL-6 Immunoassay HS600B, RD Systems Europe, Lille, France), and soluble Tumor Necrosis Factor Receptor 2 (RsTNF2) (Quantikine Human sTNFRII/TNFRSF1B Immunoassay DRT200, R&D Systems Europe, Lille, France) by enzyme-linked immunosorbent assay (ELISA). Optical densities (OD) were measured by spectrophotometry (Spectra max 190, Molecular Devices, Sunnyvale, CA).

The principal objective of the study was to evaluate the prevalence of MS in this cohort of patients. MS was defined according to new recommendations of the AHA and of the NHLBI,¹⁵ which requires the presence of three of the five following criteria: (1) hypertriglyceridemia (≥1.50 g/liter or 1.7 mmol/liter); (2) arterial hypertension (≥130/85 mm Hg); (3) low HDL-cholesterol (<0.40 g/liter or 0.9 mmol/liter for men, <0.50 g/liter or 1.1 mmol/liter for women); (4) hyperglycemia (≥1.0 g/liter or 5.6 mmol/liter); and (5) waist measurement equal to or higher than 102 cm for men and 88 cm for women. Receiving a specific treatment for hypertension, hyperglycemia, or dyslipidemia was also regarded as positive criteria.

Independent continuous data, expressed as mean±standard deviation, were compared using a Student's t test in parametric analysis or a Wilcoxon test (or Mann–Whitney) in the contrary case. As well, independent qualitative data, expressed as percentage, were compared using a Chi-square test or a Fisher's exact test. Statistical tests were regarded as significant if the p-value was lower than 0.05.

Potential predictive factors of MS were identified with univariate and multivariate logistic regression. Excluded were the parameters strongly correlated with MS definition criteria [insulin, Apo B, Apo A1, and body mass index (BMI)]. The multivariate model was built according to a downward selection procedure choosing variables with a p-value lower than 0.25 in the univariate analysis. A logarithmic transformation was carried out to satisfy the assumption of log-linearity when necessary. A Hosmer and Lemeshow test was done secondly to validate the multivariate model.

Results

Among 314 patients initially enrolled in the study, 269 fulfilled inclusion criteria and had all clinical and laboratory evaluations performed. The mean age was 43 years, 66.9% of the patients were men and 33.1% were women, and 68.3% of the patients were white and 29.5% were Africans. HT was present in 32% of the patients and current or past smokers were about 48.3%. The proportion of patients without any physical activity was 43.1%. The prevalence of metabolic syndrome by AHA and NHLBI criteria was 18.2%. Two-third (65%) of the patients with metabolic syndrome fulfilled three criteria, while 25% had four criteria for the syndrome. Patients' characteristics at the evaluation visit are shown in Table 1. Patients were divided in two groups, according to the presence or absence of MS (MS⁺ vs. MS⁻). As expected, parameters included in the definition of MS showed a significant difference between these two groups in univariate analysis (p<0.0001). Lipodystrophy was evidenced in 14/49 (29%) patients with MS vs. 25/220 (11%) of patients without MS (p<0.05): 26 patients had only lipohypertrophy, 10 only lipoatrophy, and three had both. The proportion of patients on steroids was low in both groups, and not significantly different.

Table 1.

Prevalence, Definition's Parameters, and Principal Clinical Characteristics Associated with the Metabolic Syndrome in the HIV Population of the Study

Characteristics	MS ⁻	MS ⁺	p
n (%)	220 (81.8)	49 (18.2)
Sex (male/female)	145/75	35/14	0.46
Age (years)	41 ± 10	49 ± 12	<0.0001
Alcohol consumption			0.004
Never	77 (35.0%)	16 (32.7%)
Sometimes	125 (56.8%)	21 (42.8%)
Usual	18 (8.2%)	12 (24.5%)
Tobacco smoking status			0.46
No smoker	116 (52.7%)	23 (47.0%)
Current or past smoker	104 (47.3%)	26 (54.0%)
Physical activity			0.42
Sedentary	91 (41.6%)	25 (51.0%)
Low	83 (37.7%)	14 (28.6%)
High	46 (21.0%)	10 (20.4%)
Diabetes mellitus	4 (1.8%)	7 (14.3%)	<0.0001
Dyslipidemia	29 (13.2%)	22 (44.9%)	<0.0001
Personal history of lipoatrophy	8 (3.6%)	5 (10.2%)	0.07
Personal history of lipohypertrophia	19 (8.6%)	10 (20.4%)	0.02
Personal history of cardiovascular disease (except arterial hypertension)	4 (1.8%)	1 (2.0%)	1
Family history of cardiovascular risk factors			0.02
Yes	98 (44.6%)	32 (65.3%)
No	102 (46.3%)	12 (24.5%)
Unknown	20 (9.1%)	5 (10.2%)
HBV coinfection	14 (6.4%)	1 (2.1%)	0.31
HCV coinfection	7 (3.2%)	6 (12.2%)	0.02
BMI (kg/m²)	23.6 ± 3.8	28.3 ± 5.6	<0.0001
Ethnicity			0.60
White	148 (67.6%)	35 (71.4%)
Hispanic	2 (0.9%)	1 (2.0%)
African	66 (30.1%)	13 (26.5%)
Asian	3 (1.4%)	0
Diastolic arterial tension (mm Hg)	74.7 ± 10.1	83.7 ± 11.3	<0.0001
Systolic arterial tension (mm Hg)	123.7 ± 14.7	138.2 ± 16.3	<0.0001
Waist circumference (cm)	84.6 ± 9.8	99.8 ± 13.3	<0.0001
LDL-cholesterol (mmol/liter)	3.2 ± 0.9	3.4 ± 1.0	0.02
Triglyceride (mmol/liter)	1.3 ± 0.8	2.7 ± 1.6	<0.0001
Glucose (mmol/liter)	5.0 ± 0.5	6.1 ± 1.9	0.0002
Anabolic steroid	0	0
Corticosteroid	6 (2.8%)	3 (6.1%)

Results expressed as mean (±SD) and frequency (%). Comparison of the continuous data by a Student's t test or Wilcoxon (Mann–Whitney). Comparison of the qualitative data by a Chi-square test or Fisher's exact test. p-value < 0.05.

MS, metabolic syndrome; HBV, hepatitis B virus; HCV, hepatitis C virus; BMI, body mass index; LDL, low-density lipoprotein.

HIV characteristics and immunovirological parameters are shown in Table 2. With regard to HIV classification, 51.3% of the patients were classified in category A (or asymptomatic), 24.2% in category B (or symptomatic but not AIDS diseases), and 24.5% in category C (or AIDS). The mean duration of HIV infection was 4.7 years and the mean time of exposure to antiretroviral treatment without any interruption was 29.8 months. When comparing MS⁺ and MS⁻, HIV status, duration of infection, HIV viral load, absolute CD4 cell counts, and percentage did not present significant differences. The frequency of HIV-related events was not significantly different among the two groups of patients. Inflammatory parameters showed higher plasmatic levels of hsCRP and IL-6 in the MS⁺ group than in the MS⁻ group, 4.8 vs. 3.7 mg/liter (p=0.0005) and 3.8 vs. 1.5 pg/mliter (p=0.01), respectively. No significant difference was found for RsTNF2 level (data not shown).

Table 2.

HIV Characteristics and Inflammatory Parameters Associated with the Metabolic Syndrome in the HIV Population of the Study

Characteristics	MS⁻ (n = 220)	MS⁺ (n = 49)	p
HIV stage			0.50
Asymptomatic (A)	116 (52.7%)	22 (44.9%)
Symtomatic non-AIDS (B)	53 (24.1%)	12 (24.5%)
AIDS (C)	51 (23.2%)	15 (30.6%)
Known duration of HIV infection (years)	4.7 ± 3.9	5.1 ± 4.3	0.48
Nadir CD4 (cells/mm³)	169.3 ± 118.5	146.6 ± 106.8	0.22
Actual CD4 count (cells/mm³)	437 ± 222	443 ± 260	0.85
Plasma HIV-1 RNA (copies/ml)	191 ± 1537	534 ± 2847	0.42
Plasma HIV-1 RNA < 40 copies/ml (%)	201 (91.4%)	43 (87.8%)	0.42
hsCRP (mg/liter)	3.7 ± 6.9	4.8 ± 5.3	0.0005
IL-6 (pg/ml)	1.5 ± 2.9	3.8 ± 15.7	0.01

MS, metabolic syndrome; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin 6.

In univariate analysis, no HIV parameters, including duration of exposure to HAART, was significantly associated with the risk to present MS (Table 3). An older age (OR=1.06; p<0.0001), regular alcohol consumption (OR=1.79 ; p=0.01), and HCV coinfection (OR=4.25; p=0.01) were predictive factors for MS. High levels of hsCRP (OR=1.50; p=0.01) and non-HDL-cholesterol (OR=1.92; p<0.0001) were also associated with the risk to present the MS.

Table 3.

Univariate and Multivariate Logistic Regression of the Variables Associated with the Risk to Present a Metabolic Syndrome

	Univariate ¹				Multivariate ²
Variable	N	OR	95% CI	p-value	N³	OR	95% CI	p-value
Age (per year older)	269	1.06	1.03–1.09	<0.0001	267	1.04	1.01–1.08	0.02
Usual alcohol consumption	269	1.79	1.14–2.82	0.01
Current or past smoker	269	1.26	0.68–2.34	0.46
HBV coinfection	269	3.26	0.42–25.37	0.26
HCV coinfection	269	4.25	1.36–13.26	0.01	267	5.67	1.39–23.06	0.02
Known duration of HIV infection (years)	268	1.03	0.95–1.11	0.48
Plasma HIV-1 RNA (<40 copies/ml)	269	1.48	0.56–3.92	0.43
Actual CD4 count (cells/mm³)	269	1.00	1.00–1.00	0.85
Nadir CD4 (cells/mm³)	269	1.00	1.00–1.00	0.21
hsCRP⁴	267	1.50	1.17–1.93	0.01	267	1.56	1.14–2.13	0.01
Non-HDL-cholesterol (mmol/liter)	269	1.92	1.46–2.54	<0.0001	267	1.87	1.38–2.53	<0.0001
PI cumulative exposure (per additional month)	269	1.02	1.00–1.04	0.12	267	1.03	1.00–1.06	0.02
NNRTI cumulative exposure (per additional month)	269	0.99	0.97–1.01	0.45
NNRTI+PI cumulative exposure (per additional month)	269	1.02	0.98–1.06	0.27
ABC cumulative exposure (per additional month)	269	1.02	0.99–1.04	0.13	267	1.03	1.01–1.06	0.02
AZT cumulative exposure (per additional month)	269	1.01	0.99–1.03	0.46
TDF cumulative exposure (per additional month)	269	1.00	0.98–1.03	0.79
3TC/FTC cumulative exposure (per additional month)	269	1.01	0.98–1.03	0.52

Exclusion of the factors strongly related to MS (body mass index or BMI, insulin, ApoB, and ApoA1).

Selection of variables with p-value lower than 0.25 and validation of the model by the Hosmer and Lemeshow statistical method (p=0.83).

Exclusion of two patients for missing data (hsCRP).

Logarithmic transformation to satisfy the assumption of loglinearity of the model.

MS, metabolic syndrome; HBV, hepatitis B virus; HCV, hepatitis C virus; hsCRP, high-sensitivity C-reactive protein; HDL, high-density lipoprotein; PI, protease inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; ABC, abacavir; AZT, zidovudine; TDF, tenofovir; 3TC/FTC, lamivudine/emtricitabine.

Higher age, hsCRP, and non-HDL-cholesterol emerged as significantly and independently associated with MS in the logistic regression model (Table 3) (OR=1.04; OR=1.56 and OR=1.87, respectively). The multivariate analysis also showed an association between HCV coinfection (OR=5.67; p=0.02), a prolonged exposure to PIs (OR=1.03; p=0.02), or abacavir (ABC) (OR=1.03; p=0.02), and the risk of having MS.

The most common ritonavir-boosted protease inhibitors during the study were lopinavir (55%), indinavir (18%), and fosaprenavir (16%). When LPV/r was compared to other PI/r, as a group, cumulative exposure to LPV/r was associated with MS (p=0.0283), while exposure to other PI/r was not.

Discussion

The emergence of clinical and biological modifications observed in HIV-infected patients receiving HAART (insulin resistance, dyslipidemia, lipodystrophy) has recently emphasized interest in the diagnosis of MS in this population. Initially, MS was primarily described in patients with diabetes or with risk factors for cardiovascular disease,^15
–17 and its presence in HIV-infected patients was only recently reported.^9,18 In our cross-sectional study of 269 HIV-infected patients recently initiated on antiretroviral therapy, with a median duration of around 30 months of treatment, 18.2% of the patients presented a positive diagnosis of MS, known as a predictive and independent marker of morbidity and mortality from cardiovascular diseases.³ Such a prevalence, quite similar to the one observed in a previous study,¹⁴ places HIV-infected patients receiving HAART in a high-risk cardiovascular disease category population. By comparison, its prevalence was similar in diabetic patients presenting angiographic coronary abnormalities, whereas its prevalence in a healthy population was only 5%.¹⁹ In our study, prevalence was calculated according to new American recommendations established by the AHA-NHLBI, which includes antihypertensive, hypolipemic, or hypoglycemic treatment as positive criteria.¹⁵ The choice of the AHA-NHLBI recommendations seems important regarding the frequent prescription of these treatments to HIV-infected patients receiving HAART. The prevalence we observed using these new criteria did not differ from the prevalence reported using traditional criteria of NCEP-ATP III.^9,18,20 No significant difference was observed regarding HIV disease history or immunovirological status when MS⁺ and MS⁻ patients where compared, which suggests the absence of a direct role of HIV on this syndrome.

Changes in body fat compartmentalization,⁷ modification of lipidic metabolism (hypertriglyceridemia, diminution of HDL-cholesterol),²¹ and perturbation of glucose metabolism in cells are largely described as PI-adverse effects.^22,23 Recent studies highlighted the role of HAART and particularly PIs in the mechanism of MS occurrence.^9,20 In this context, our data confirm this association, showing a moderate increase in the risk of presenting an MS when exposure to a PI is prolonged (OR=1.03; p=0.02). Such an association has been well characterized for lopinavir, our results being consistent with previous data despite the limited power of our analysis.²⁰ Abacavir (ABC) exposure has been associated with increased cardiovascular disease and higher levels of inflammatory markers, i.e., hsCRP and IL-6.^24,25 Other studies failed to demonstrate abnormalities of inflammation markers in ABC-treated patients.^26,27 Such an association between ABC exposure and risk of myocardial infarction has been challenged in a recent meta-analysis.²⁸ Our analysis suggests a moderate but significant relation between ABC cumulative exposure and a relative increased risk of presenting an MS (OR=1.03; p=0.02). We cannot exclude that this association was due to an indication bias and that the presence of MS was the cause rather than the consequence of ABC use. Indeed, with the design of such a cross-sectional observational study, we cannot assess whether patients with hyperlipidemia before or during antiretroviral therapy might have been preferentially prescribed ABC. At the time of treatment initiation for the patients included in this study, there was an emphasis on the beneficial effects of ABC on lipid parameters.²⁹

Analysis of the inflammatory component of MS is an original part of our study. Atherosclerosis is considered to be an inflammatory disease,³⁰ with CRP and IL-6 levels being independent predictors of cardiovascular diseases.³¹ In our study, we demonstrate a significant increase of these parameters in the population of patients with MS. These results are in agreement with data emphasizing hsCRP level as a predictive and independent marker of MS development.³² The role of IL-6 in the pathophysiology of MS could be through a decrease of HDL-cholesterol and Apo A1 synthesis in the liver.³³ The increase of hsCRP is associated with the presence of cardiovascular risk factors in HIV-infected patients on antiretroviral therapy.³⁴

In addition, HCV infection increases the risk of presenting an MS in our population by five-fold. This observation coincides with recent results showing a correlation between HCV infection and an increased risk of cardiovascular disease among HIV-infected patients.^35,36 Such an association could be the consequence of steatohepatitis, which leads to insulin resistance.

One of the limitations of our results is the observational design of our study and a rather limited population, which reduces the statistical power of some analyses, especially exposure to antiretrovirals. HCV infection was assessed based on serological results and HCV RNA was not available. This could also be a limitation, although most HIV patients with HCV coinfection have HCV viremia.

On the other hand, our study emphasizes the importance for clinicians to proactively detect the MS for any HIV-infected patients on antiretroviral therapy for more than 1 year. Such an evaluation should probably also be done before any initiation of antiretroviral treatment. As a matter of fact, use of specific therapeutics known to reduce cardiovascular risk, and statins in particular,^37,38 might benefit these patients by preventing long-term metabolic and cardiovascular complications.

In conclusion, the SYMET study confirms that HIV-infected patients treated with potent antiretroviral therapy show a high prevalence of MS (18.2%). MS was associated with insulin resistance, inflammation, HCV coinfection, and prolonged exposure to some antiretrovirals. The influence of exposure to PIs and ABC is highlighted in this study, although potential indication bias cannot fully be ruled out. Our results emphasize the multifactorial aspect of the metabolic syndrome. In addition to the role of traditional cardiovascular risk factors (hypertension, age, body mass index, consumption of tobacco), susceptibility to developing an MS for HIV-infected patients on antiretroviral therapy is increased by the chronic inflammation associated with HIV infection, by HCV coinfection, and by long-term exposure to some antiretrovirals. The clinical diagnosis of MS in HIV-infected patients should lead clinicians to different ways to optimize its management and prevent cardiovascular disease including smoking cessation, physical activities, hypolipidemic treatment such as statins, antihypertensive treatment, and/or changes in antiretroviral combination therapy.

Footnotes

Acknowledgments

The study was supported by SIDACTION and ARSIID.

Author Disclosure Statement

No competing financial interests exist.

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