Version May 2024
INTRODUCTION — As people with HIV have a near normal lifespan with treatment, cardiovascular disease has emerged as an important cause of morbidity and mortality. Even with effective antiretroviral therapy (ART), people with HIV have a higher risk of myocardial infarction and cardiovascular death than age-matched uninfected controls. The excess risk of myocardial infarction in people with HIV remains elevated compared to the general population, despite improvements in HIV treatment [1]. Traditional risk factors, such as smoking, hypertension, and dyslipidemia, contribute substantially to this higher risk [2], but there is also evidence that HIV infection and, to a lesser extent, its treatment are directly linked to atherogenesis, endothelial dysfunction, and coagulation abnormalities, probably through inflammation and immune dysregulation.
Measures of subclinical cardiovascular disease and the pathogenesis of atherosclerosis in patients with HIV are discussed here. The epidemiology of cardiovascular morbidity and traditional risk factors and the management of dyslipidemia and cardiovascular risk in patients with HIV are addressed elsewhere. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV" and "Management of cardiovascular risk (including dyslipidemia) in patients with HIV".)
SUBCLINICAL ATHEROSCLEROSIS — Cardiovascular disease has emerged as an important cause of death in patients with HIV, as illustrated by clinical studies evaluating such hard endpoints as stroke or myocardial infarctions (see "Epidemiology of cardiovascular disease and risk factors in patients with HIV"). However, people with HIV, especially those who are younger, have overall low short-term cardiovascular risk and few events. Therefore, many clinical studies rely upon surrogate markers to indirectly assess the burden of cardiovascular disease. These studies have generally demonstrated an increased prevalence of subclinical atherosclerosis in individuals with HIV compared to those without. Such measurements include intima media thickness (IMT) and intraluminal arterial plaque as assessed by ultrasound and evaluation of coronary artery calcification and plaque by computed tomography (CT). These measurements have been moderately associated with coronary atherosclerosis and the future risk of a cardiovascular event in studies of uninfected adults [3]. (See "Overview of possible risk factors for cardiovascular disease", section on 'Arterial intima-media thickness' and "Overview of possible risk factors for cardiovascular disease", section on 'Coronary artery calcification'.)
Evidence of increased subclinical atherosclerosis among elite controllers with HIV compared with uninfected controls has also been observed, suggesting that an increased risk of atherosclerosis can occur in the absence of antiretroviral therapy (ART), detectable viremia, or overt immunodeficiency [4-6].
Intima media thickness — Most, but not all studies of IMT of the carotid artery and coronary arteries in asymptomatic adults have found an increase in measurement with HIV infection [4,7-16]. In a meta-analysis of observational studies evaluating subclinical atherosclerosis in patients with HIV, the following observations were noted [7]:
●Among the 13 studies that compared carotid IMT in patients with HIV versus those without, all except for two reported a trend towards higher carotid IMT with HIV. However, the weighted mean difference between patients with HIV and patients without HIV was very small, 0.04 mm (95% CI 0.02-0.06). Moreover, there was significant statistical and clinical heterogeneity between the studies, including differences in measurement technique and underlying traditional cardiovascular risk factors.
●There was no difference in the weighted means of carotid IMT measurements from 12 studies comparing patients with HIV and with or without protease inhibitor exposure.
●There was evidence of selection bias, with small studies showing an effect of HIV infection and larger studies showing lack of difference.
Despite the limitations of the meta-analysis, several subsequent large observational studies supported its findings and reported even larger increases in IMT with HIV infection [4,8]. The association between HIV infection and IMT may be modulated by age. In a study of over 1700 patients with HIV, carotid IMT was higher compared with age-matched uninfected controls among individuals aged 6 to 29 years but was similar to controls among adults 30 years and older, among whom IMT correlated more strongly with traditional risk factors [17]. However, other studies have noted higher IMT among patients with HIV, even when adjusted for age [8].
Effect of antiretroviral therapy on intima media thickness — The effect of ART on IMT appears to vary by agent. As an example, in a randomized trial, atazanavir was associated with a slower rate of progression of carotid IMT compared with darunavir; this difference was hypothesized to be related to the fact that atazanavir increases bilirubin, which may exert an antioxidant effect that slows the progression of atherosclerosis [18]. The effect of raltegravir was intermediate. An observational study of 102 ART-naïve patients demonstrated comparable progression of carotid IMT over two years among those who started on tenofovir alafenamide/emtricitabine plus either raltegravir, elvitegravir/cobicistat, or dolutegravir [19].
Coronary artery calcification and plaque — Studies suggest that individuals with HIV may not have a greater burden of coronary artery calcification than uninfected patients after controlling for traditional cardiovascular risk factors but are more likely to have non-calcified atherosclerotic plaque, which may be more likely to rupture.
Additional studies have evaluated coronary artery calcification, which is detected by CT, in patients with HIV. In the meta-analysis discussed above, there was no difference in coronary artery calcification between people with HIV and people without HIV in the pooled results from five studies [7]. However, some but not all [20] subsequent studies using CT angiography to assess overall plaque burden have reported a higher prevalence among people with HIV compared to those without HIV with similar Framingham risk scores [21-25]. As an example, in a multicenter observational study of 450 HIV-infected and 309 uninfected men who have sex with men between the ages of 40 and 70 years, HIV infection was associated with a higher prevalence of plaque in any coronary segment, as detected by CT angiography, even after adjustment for age, race, and traditional cardiovascular risk factors (prevalence ratio [PR] 1.13, 95% CI 1.04-1.23) [24]. Specifically, individuals with HIV had a higher adjusted prevalence and extent of non-calcified plaque, which was associated with advanced age, lower nadir CD4 cell count, and longer duration of ART. The majority of the men with HIV in this study were on ART. Statin therapy appears to ameliorate this finding. In a prospective study of individuals with HIV, treatment with atorvastatin was associated with improvement in non-calcified plaque volume [26].
The prevalence of plaque among people with HIV with estimated low to moderate ASCVD risk was reported from a baseline analysis of the CT substudy in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among people with HIV [27]. Plaque was reported in nearly half of the participants. Although luminal obstruction of more than 50 percent was rare (3 percent), vulnerable plaque was observed in 23 percent of patients. Follow-up data from this cohort will further elucidate the factors associated with progression of plaque.
PATHOGENESIS OF VASCULAR DISEASE — The development of atherosclerosis that underlies cardiovascular disease and events is a complicated and multifactorial process that involves inflammation and immune dysregulation, endothelial dysfunction, and plaque rupture, as well as the traditional risk factors of hypertension, diabetes, dyslipidemia, and smoking. (See "Pathogenesis of atherosclerosis".)
This section discusses markers of inflammation, endothelial function, and coagulation that have been associated both with HIV infection as well as with progression to atherosclerosis or cardiovascular events in the general population. Although a number of abnormalities in soluble and cellular markers have been associated with cardiovascular disease in patients with HIV, there are none that have been validated yet for clinical use.
The prevalence of traditional risk factors in patients with HIV is discussed elsewhere. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV", section on 'Traditional risk factors'.)
Inflammation — Inflammation plays a pivotal role in the development of atherosclerosis in general and is an area of active research with regards to HIV infection. Active inflammation may adversely affect endothelial cells and promote a prothrombotic environment that leads to atherosclerosis and plaque rupture. HIV infection has been linked to several markers of inflammation, including C-reactive protein (CRP) and interleukin (IL)-6, which in turn have been associated with cardiovascular events.
Imaging studies — Through positron emission tomography (PET) imaging, arterial inflammation can be detected by increased uptake of a radiolabeled glucose analog, fluorodeoxyglucose (FDG), in blood vessels. In one study of 27 patients with HIV (mean age 52 years) on antiretroviral therapy (ART) and without known cardiac disease, PET imaging was performed and compared with the findings in uninfected patients who underwent PET imaging for other reasons [28]. Arterial inflammation in the aorta among patients with HIV was higher compared with uninfected patients who also had no known cardiac disease and were matched by age, sex, and Framingham risk score but was similar to that seen in sex-matched uninfected patients (mean age, 69 years) who had known atherosclerotic disease. Although aortic inflammation was not associated with levels of CRP and D-dimer, it did correlate with sCD163, a soluble marker of monocytes and macrophage that has been associated with atherosclerosis in uninfected populations.
Soluble markers
C-reactive protein — CRP is the most extensively studied of numerous inflammatory biomarkers potentially linked to underlying atherosclerosis in the general population, among whom elevations in CRP are associated with an increased risk of cardiovascular events independent of traditional risk factors. (See "C-reactive protein in cardiovascular disease".)
HIV infection has been associated with increased CRP levels when compared with uninfected controls [29]. Furthermore, in a study of 922 patients with HIV followed for five years, a high CRP was independently associated with increased overall mortality [30]. With regards to the specific morbidity of cardiovascular disease, the association between CRP levels and myocardial infarction risk in patients with HIV was evaluated in a study of a large hospital database that included 487 patients with HIV and 69,870 patients without HIV [31]. High CRP (any value exceeding the upper limit of normal of the standard assay or any value in the highest quantile of the high sensitivity CRP assay) was found more frequently among patients with HIV (59 versus 39 percent). In an adjusted model controlling for age, sex, race, hypertension, diabetes and dyslipidemia, the risk for acute myocardial infarction was increased more than fourfold among patients with HIV infection and increased CRP when compared with patients with neither risk factor. There was no association between CRP level and HIV viral load or CD4 cell count, but protease inhibitor use was associated with high CRP levels.
The effect of ART in general on CRP is unclear, with some studies showing an increase [32] and others showing a decrease [33]. Changes in CRP level may depend on the particular agent used [34-36]. In a study of 244 patients who had been randomly assigned to initiate one of four ART regimens, increases in CRP at weeks 24 and 96 were observed with regimens containing abacavir-lamivudine, particularly when used with efavirenz, in contrast to stable levels with tenofovir-emtricitabine or boosted atazanavir [37]. This finding was notable because of an apparent increase in myocardial infarction risk seen with abacavir in a large cohort of patients with HIV (see "Epidemiology of cardiovascular disease and risk factors in patients with HIV", section on 'Abacavir'). However, this study did not analyze the association of such changes in CRP with cardiovascular events, and in fact, the two participants who experienced a myocardial infarction during the study period were receiving tenofovir-emtricitabine and efavirenz. In other studies among patients who had been on long-term ART, changes in biomarkers of inflammation were more likely to be related to personal factors such as smoking and obesity than ART [38].
It is unclear whether the association between CRP and cardiovascular events in individuals with HIV differs from that among the uninfected population [39].
Interleukin-6 — Increased levels of the proinflammatory cytokine IL-6 are thought to have a direct causal role in the development of coronary heart disease among the general population (see "Overview of established risk factors for cardiovascular disease", section on 'Interleukin-6') and have been observed in patients with HIV infection, particularly with more advanced disease. In a study of 1525 veterans with HIV, there was no overall difference in prevalence of increased IL-6 compared with 843 uninfected controls after controlling for age and race [40]. However, there was a greater association with increased IL-6 levels compared with the uninfected in the setting of an HIV viral load ≥500 copies/mL (odds ratio [OR] 1.54, 95% CI 1.14-2.09) or a CD4 cell count <200 cells/microL (OR 2.25, 95% CI 1.60-3.16). Furthermore, in post hoc analyses of participants in the SMART trial, which evaluated ART continuation versus treatment interruption based on CD4 cell count, increased levels of IL-6 were associated with HIV RNA viremia, cardiovascular events, and all-cause mortality [41,42]. A subsequent small study suggested that elevations in IL-6 were associated with endothelial dysfunction as reflected by changes in small artery elasticity and endothelial adhesion molecules [43]. Finally, in a post hoc analysis of samples from two completed HIV trials, IL-6 was a stronger predictor of cardiovascular events than D-dimer [44].
In the cross-sectional CT angiography study noted above from the REPRIEVE trial, LpPLA2 and IL-6 levels were associated with the presence of coronary plaque after adjustment for traditional risk factors and CD4 count and HIV RNA.
Cellular activation
T cell activation — Activation of T cells is a hallmark of HIV infection and levels of activated CD4 and CD8 T cells have been linked to rates of disease progression. During effective ART, levels of activation fall, but not back to pre-HIV levels in most patients, at least during the first few years of treatment. Studies examining the relationship between T-cell activation and atherosclerosis in HIV infection have yielded inconsistent results. Cross-sectional studies have demonstrated associations between the proportion of activated and senescent CD8 T cells and carotid intima media thickness and carotid lesions [45-48].
Monocyte activation — Several lines of evidence suggest that monocyte activation may contribute to the development of atherosclerosis in HIV [28,45,49-54]. Soluble CD163, the extracellular component of the hemoglobin-haptoglobin receptor CD163, is released from activated monocytes and macrophages during inflammation. Both aortic inflammation and soft plaque volume in patients with HIV have correlated with sCD163 [28,49]. In addition, sCD14 levels were associated with progression of carotid intima media thickness (IMT) in a small study [50]. Several studies have reported increased levels of innate immune activation during treated HIV infection and associations between cellular measures of activated monocyte populations and carotid IMT in HIV [45,51,52]. Additionally, progression of coronary-artery calcium has been associated with higher frequencies of activated monocytes, but not tissue factor expression, T-cell activation, or senescence phenotype [53].
Endothelial dysfunction
Arterial dynamics — In a clinical trial of treatment-naïve subjects randomly assigned to initiate various ART regimens, there was a rapid and significant improvement in flow-mediated dilation of the brachial artery, a measure of endothelial function, during the first 24 weeks of therapy [55]. This improvement in flow-mediated dilation was seen regardless of regimen, suggesting that suppression of HIV, and not the specific drugs themselves, led to improved endothelial function [56]. Another study used noninvasive measurement of radial pulse waveforms to assess large and small artery elasticity in 32 treatment-naïve individuals with HIV and 30 individuals without HIV [57]. After adjusting for risk factors, including the Framingham 10-year cardiovascular disease risk score, those with HIV infection demonstrated significantly less elasticity in both large and small arteries when compared with the uninfected group. These data suggest that chronic HIV infection, independent of its pharmacologic treatment, induces alterations of endothelial function.
However, there is evidence for endothelial dysfunction in patients with HIV on therapy as well. Increased pulse wave velocity, which may be an early marker for atherosclerosis, has been noted in two small studies of patients with HIV taking ART compared with uninfected controls [58,59]. Cumulative duration of ART exposure was associated with an incremental increase in velocity, supporting a role of HIV therapy in the pathogenesis of endothelial dysfunction.
Certain antiretroviral agents may be more highly associated with abnormal endothelial function than others. In uninfected individuals, the use of indinavir was associated with endothelial dysfunction, independent of drug-induced alterations in blood pressure or lipid profiles [60]. However, in contrast to the dramatic impairment seen with indinavir, atazanavir and lopinavir did not induce endothelial dysfunction in 18 healthy subjects in another small study [61]. These data suggest that any endothelial dysfunction related to protease inhibitors is drug specific and not class specific.
One small study of 61 patients on ART suggested that abacavir may be associated with endothelial dysfunction as assessed by flow-mediated dilation, which may underlie the observed increased risk of myocardial infarction among abacavir-treated patients [62].
Plasma markers of endothelial function — In a longitudinal study of patients newly infected with HIV, measures of endothelial activation (ICAM-1 and VCAM-1) were increased early after HIV acquisition [63]. Additionally, in the absence of ART during chronic infection, plasma VCAM-1 levels were independently associated with time to HIV progression or death.
In a retrospective cohort study of 56 patients with HIV starting an ART regimen based on either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor, serum markers of endothelial dysfunction (eg, monocyte chemoattractant protein, P-selectin, vascular cell adhesion molecule, and von Willebrand factor) declined similarly with either treatment approach [64]. By contrast, increased levels of these markers were observed at baseline and 3, 6, and 12 months of follow-up in a control cohort of 10 untreated patients with HIV and CD4 cell counts >500 cells/mm3. Compared with patients with HIV, healthy controls had significantly lower levels of all measured markers at every time point.
Similarly, in a subset analysis of patients with HIV randomly assigned to start ART immediately (n = 134) or to delay ART initiation until warranted by HIV disease progression (n = 114), the levels of asymmetric dimethylarginine (ADMA), an inhibitor of the nitric oxide synthase pathway that reflects endothelial dysfunction and may be an independent risk factor for cardiovascular disease, changed more favorably after 12 months with immediate ART administration [65]. (See "Overview of possible risk factors for cardiovascular disease", section on 'Asymmetrical dimethylarginine'.)
However, other studies have shown that antiretroviral medications also contribute to aberrations in levels of markers of endothelial function, such as soluble endothelial adhesion molecules [60,66-69]. In one study, plasma P-selectin and t-PA were measured in 60 patients on ART and 60 treatment-naïve patients. Significantly higher levels of both markers were found in those taking ART [66].
These clinical studies of altered endothelial function in HIV infection are supported by in vitro and animal studies. A preliminary report from a study examining aortic tissue from the simian immunodeficiency virus (SIV) macaque model reported focal endothelial proliferation and infiltration of monocytes, T lymphocytes, and platelets in three of the four SIV infected animals, compared with none of the uninfected controls [70]. In addition, there were reduced levels of factors that promote an antithrombotic environment in the endothelium (Krüppel-like factor 2 [KLF2] and endothelial nitric oxide synthase). In an AIDS murine model, vascular smooth muscle tone is reduced as early as the first week after retroviral infection, suggesting vascular dysfunction precedes the onset of significant immunodeficiency [71]. This effect may be mediated by vascular endothelial nitric oxide dysregulation and prostacyclin-induced vasodilation [72]. In vitro studies have demonstrated that HIV-associated proteins, such as gp120 and Tat (transactivator of viral replication), are toxic to vascular or cardiac cell lines [73,74].
Abnormalities of coagulation — In addition to endothelial dysfunction, there is also evidence of a dysregulation of coagulation and fibrinolysis, which have been linked to cardiovascular disease in the general population.
Several studies have described increased plasma levels of endothelial cell products, including von Willebrand factor and soluble thrombomodulin, and the fibrin degradation product D-dimer in those living with HIV, and these levels are noted to inversely correlate with CD4 counts [40,75-77]. A positive correlation has also been noted between HIV viral load and prothrombin fragment in 90 individuals with HIV (mean age 38 ± 9 years, mean CD4 216 ± 198) not receiving ART, which suggests that increasing levels of viremia may increase the risk for thrombosis [78].
Moreover, increased D-dimer levels in the setting of treatment interruption and increased fibrinogen levels have been associated with increased mortality in patients with HIV [30,41]. Additionally, in a case-control study of patients with HIV who had experienced a cardiovascular event (n = 52) or had not (n = 104), D-dimer was independently associated with cardiovascular event risk [79].
However, not all changes in markers of coagulation in the setting of HIV infection suggest a hypercoagulable state. In a study of 278 males with HIV, levels of antithrombin were higher and levels of a functional measure of thrombin generation were lower compared with 39 uninfected controls [80].
Furthermore, it is unclear what the impact of ART is on coagulation. One study of 1131 patients with HIV and 281 controls found that protease inhibitor use was associated with higher fibrinogen levels (with the strongest associations for indinavir and ritonavir), whereas non-nucleoside reverse transcriptase inhibitor use was associated with lower fibrinogen levels [81].
Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) may play a role in the pathogenesis of atherosclerosis in HIV infection [82]. Chronic immune stimulation increases TF expression on the surface of monocytes. In a study of 121 adults with HIV, higher concentrations of TF were associated with subclinical atherosclerosis (assessed by carotid intima media thickness) and correlated with longer duration of ART and lower nadir CD4 counts [83].
Other factors associated with atherosclerosis
Viral co-infection — The presence of ongoing inflammation secondary to the presence of other chronic viral infections may also promote the development of atherosclerosis and subclinical cardiovascular disease in patients with HIV.
Asymptomatic infection with cytomegalovirus (CMV) has been associated with cardiovascular morbidity in both those with HIV and those without HIV. In a study of 6111 individuals with HIV, of whom 5119 (82 percent) were seropositive for CMV, seropositivity was independently associated with non-AIDS events, including cardiovascular and cerebrovascular diseases [84]. Studies evaluating the pathogenesis of this association have suggested a potential role in atherogenesis. In a study of 93 patients with HIV (91 percent men and 94 percent on ART), greater CD4 and CD8 T-cell responses against CMV were independently associated with increased carotid IMT [85]. In a separate study of 601 women with HIV and positive CMV immunoglobulin G (IgG) serology, higher levels of CMV IgG were independently associated with carotid artery stiffness but not carotid IMT as measured by carotid ultrasound [86]. No such association was seen in 90 uninfected controls matched for age and race. That study also found that CMV IgG levels were associated with carotid artery lesions only among patients with HIV who had viral suppression on ART, not those who were untreated or continued to be viremic despite ART. This suggests that decreased HIV viral replication may be mediating the relationship between an enhanced immune response against CMV and vascular disease. In contrast, a recent cross-sectional analysis from the REPRIEVE cohort (a predominantly virologically suppressed cohort) found no association between CMV IgG titer and presence of plaque, coronary artery calcium (CAC) score >0, or the presence of vulnerable plaque [87].
Other viruses that have been implicated in the development of subclinical cardiovascular disease in patients with HIV include herpes simplex virus 2 (HSV-2) [88]. Coinfection with Hepatitis C virus (HCV) has been linked to endothelial dysfunction [89] and modulates known risk factors for cardiovascular disease in patients with HIV, but it is not clear if HCV increases their risk of myocardial infarction [90-92]. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV", section on 'Hepatitis C virus infection'.)
Vitamin D — Vitamin D deficiency in patients with HIV has been linked to indirect markers of subclinical atherosclerotic cardiovascular disease, including carotid IMT and brachial artery flow-mediated dilation [51,93-95].
However, it is unclear whether replacing vitamin D improves cardiovascular outcomes. Studies evaluating the effect of vitamin D supplementation on indirect measures of atherosclerosis (eg, brachial artery flow-mediated dilation and carotid IMT) are conflicting [96,97]. In a trial of 45 adults with HIV and viral suppression on ART who had vitamin D levels <20 ng/mL, there was no significant change in brachial artery flow-mediated dilation at 12 weeks in the 30 patients randomly assigned to daily supplementation with 4000 international units cholecalciferol or in the 15 patients assigned to placebo [96]. Furthermore, other than a small decrease in the IL-6 level in those taking supplementation, there were no differences between the two groups in other markers of endothelial dysfunction, coagulation function, or inflammation. Of note, the patients in the supplementation group experienced a mere 5 ng/mL increase in the vitamin D level. In another small randomized trial in HIV-positive youth, standard-dose vitamin D supplementation decreased carotid IMT over 24 months, whereas high-dose supplementation increased it [97].
EPIGENETIC MODIFICATION — Epigenetic modification (chemical alteration to DNA that does not affect the sequence but may change the expression or regulation of genes) is a potential predictor of risk for chronic diseases, including cardiovascular disease [98]. Studies in HIV pathogenesis suggest that chronic HIV infection can lead to epigenetic modification [99]. Subsequent data from several cohort studies among individuals with HIV have identified markers of DNA methylation consistent with accelerated aging [100] and have linked these changes to risk factors for future cardiovascular disease [101,102]. Continued research into these measures for predicting future risk appears promising. (See "Principles of epigenetics".)
SUMMARY
●Subclinical atherosclerosis – Studies that rely on measures of subclinical atherosclerosis, such as carotid intima media thickness (IMT) and coronary artery plaque on imaging, suggest an increased prevalence of cardiovascular disease in patients with HIV, and cardiovascular disease has emerged as an important cause of morbidity and mortality in this population. (See 'Subclinical atherosclerosis' above and "Epidemiology of cardiovascular disease and risk factors in patients with HIV".)
●Pathogenesis of vascular disease
•Cellular activation and endothelial dysfunction – HIV infection is associated with increased soluble and cellular markers of inflammation, endothelial dysfunction, and altered coagulation, all of which have been shown to contribute to cardiovascular disease. The strongest associations have been between measures of innate immune activation and cardiovascular disease. The effect of antiretroviral therapy (ART) on these markers is less clear. (See 'Inflammation' above and 'Cellular activation' above and 'Endothelial dysfunction' above and 'Abnormalities of coagulation' above.)
•Traditional risk factors – Traditional cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking, also contribute substantially to the pathogenesis of cardiovascular disease in patients with HIV. Their prevalence among patients with HIV is discussed elsewhere. (See "Epidemiology of cardiovascular disease and risk factors in patients with HIV", section on 'Traditional risk factors'.)
ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.
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