Cardiovascular Disease In HIV-infected Patients Research Articles

Assessment of Cardiovascular Risk and Arterial Stiffness in Patients With Human Immunodeficiency Virus.

Several studies suggest that patients infected with the human immunodeficiency virus (HIV) under highly active antiretroviral therapy (HAART) have a higher cardiovascular risk than the general population. Arterial stiffness is an independent predictor of cardiovascular events and can be measured through carotid-femoral pulse wave velocity (PWV). The objectives of this study were to characterize a sample of HIV-infected patients under HAART regarding cardiovascular risk, compare PWV values of this group with those of uninfected controls,and investigate predictors of PWV in the HIV-infected group. PWV was measured, and data was collected from a sample of 125 HIV-infected patients under HAART. PWV measurements in the study group were compared with those in a control group of 250 subjects similar in sex, age, prevalence of hypertension, and type 2 diabetes mellitus (DM). A linear regression model was constructed to identify predictors of PWV in the HIV-infected group. In the HIV-infected group, composed mostly of men, the mean age and respective standard deviation were 48.6 ± 11.6 years. In this group, 112 individuals (89.6%) presented moderate to very high cardiovascular risk. Significant differences were found in median PWV between HIV-infected and control groups (8.56 vs. 8.00 m/s,p= .002). Age, peripheral systolic blood pressure, presence of DM, amount of alcohol consumed, and current CD4+T cell count were independent predictors of PWV in the HIV-infected group. Conclusions: The HIV-infected group showed higher cardiovascular risk and arterial stiffness measurements than the general population. PWV may be an important predictor of subclinical cardiovascular disease in HIV-infected patients.

Lights and Shadows of Microbiota Modulation and Cardiovascular Risk in HIV Patients.

Human immunodeficiency virus (HIV) infection is associated with premature aging and the development of aging-related comorbidities, such as cardiovascular disease (CVD). Gut microbiota (GM) disturbance is involved in these comorbidities and there is currently interest in strategies focused on modulating GM composition and/or functionality. Scientific evidence based on well-designed clinical trials is needed to support the use of prebiotics, probiotics, symbiotics, and fecal transplantation (FT) to modify the GM and reduce the incidence of CVD in HIV-infected patients. We reviewed the data obtained from three clinical trials focused on prebiotics, 25 trials using probiotics, six using symbiotics, and four using FT. None of the trials investigated whether these compounds could reduce CVD in HIV patients. The huge variability observed in the type of compound as well as the dose and duration of administration makes it difficult to adopt general recommendations and raise serious questions about their application in clinical practice.

HIV-associated cardiovascular pathology

The review presents the rationale for studying cardiovascular disease in HIV-infected patients, as well as the importance of specific therapy. The embrace of this problem is due the widespread use of antiretroviral therapy in the world over the past 20 years has led to an increase in the life expectancy of HIV patients, while cardiovascular diseases have become a mortality and disability leader. The review presents the most frequently reported cardiovascular pathology and cardiac complications in HIV patients that occur both against the background of virus-mediated action and as a result of antiretroviral therapy. Some pathogenetic mechanisms of HIV influence on cardiomyocytes and the extracellular matrix have been demonstrated, resulting in early heart failure and pulmonary hypertension. Information is given on the role of statins in the management of HIV patients with the clinically significant atherosclerosis.

HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease.

With the success of antiretroviral therapy (ART), a dramatic decrease in viral burden and opportunistic infections and an increase in life expectancy has been observed in human immunodeficiency virus (HIV) infected individuals. However, it is now clear that HIV- infected individuals have enhanced susceptibility to non-AIDS (Acquired immunodeficiency syndrome)-related complications such as cardiovascular disease (CVD). CVDs such as atherosclerosis have become a significant cause of morbidity and mortality in individuals with HIV infection. Though studies indicate that ART itself may increase the risk to develop CVD, recent studies suggest a more important role for HIV infection in contributing to CVD independently of the traditional risk factors. Endothelial dysfunction triggered by HIV infection has been identified as a critical link between infection, inflammation/immune activation, and atherosclerosis. Considering the inability of HIV to actively replicate in endothelial cells, endothelial dysfunction depends on both HIV-encoded proteins as well as inflammatory mediators released in the microenvironment by HIV-infected cells. Indeed, the HIV proteins, gp120 (envelope glycoprotein) and Tat (transactivator of transcription), are actively secreted into the endothelial cell micro-environment during HIV infection, while Nef can be actively transferred onto endothelial cells during HIV infection. These proteins can have significant direct effects on the endothelium. These include a range of responses that contribute to endothelial dysfunction, including enhanced adhesiveness, permeability, cell proliferation, apoptosis, oxidative stress as well as activation of cytokine secretion. This review summarizes the current understanding of the interactions of HIV, specifically its proteins with endothelial cells and its implications in cardiovascular disease. We analyze recent in vitro and in vivo studies examining endothelial dysfunction in response to HIV proteins. Furthermore, we discuss the multiple mechanisms by which these viral proteins damage the vascular endothelium in HIV patients. A better understanding of the molecular mechanisms of HIV protein associated endothelial dysfunction leading to cardiovascular disease is likely to be pivotal in devising new strategies to treat and prevent cardiovascular disease in HIV-infected patients.

Coronary artery calcium and intima-media thickness are associated with level of cytomegalovirus immunoglobulin G in HIV-infected patients.

Coinfection with cytomegalovirus (CMV) may be involved in cardiovascular disease in HIV-infected patients. We found that higher level of CMV immunoglobulin G (IgG) was independently associated with an increased risk of coronary artery calcium and higher intima-media thickness in HIV-infected patients but not in healthy controls after adjustment for other cardiovascular risk factors and levels of herpes viridae IgG.

Effects of Chinese herbal medicine on hyperlipidemia and the risk of cardiovascular disease in HIV-infected patients in Taiwan

Ethnopharmacological relevanceDue to the development of antiretroviral therapy (ART), HIV/AIDS is now regarded as a treatable chronic disease. Chinese herbal medicine (CHM) is a type of complementary and alternative medicine (CAM) that has been widely applied in the healthcare system in Taiwan. Aim of the studyThe aim of this study was to investigate the frequency of use and patterns of prescription for the CHM-based treatment of HIV-infected patients and to assess the long-term effects of CHM on hyperlipidemia and cardiovascular disease events in these patients. Materials and methodsWe identified 21,846 HIV-infected patients (ICD-9-CM: 042-044, 079, and V08 codes). Of these, 1083 and 2166 patients who used CHM and were non-users, respectively, were matched for age, gender, and ART use before CHM. The chi-squared test, Cox proportional hazard model, Kaplan-Meier method, and the log-rank test were used for comparisons between these two groups. ResultsCHM users had a lower risk of hyperlipidemia compared with non-users after adjusting for comorbidities by using a multivariate Cox proportional hazard model (P = 0.0011; HR: 0.66, 95% CI: 0.52–0.85). In addition, the CHM users had a lower risk of cardiovascular disease compared with non-users after adjusting for comorbidities (P = 0.0004; HR: 0.67, 95% CI: 0.53–0.83). The 10-year cumulative incidences of hyperlipidemia and cardiovascular disease were lower in the CHM group (P < 0.0001 for both, log rank test). Among the 12 most commonly used CHMs in these patients, Jia-Wei-Xiao-Yao-San (JWXYS) (46.1%), Ge-Gen-Tang (GGT) (40.6%), and Yin-Qiao-San (YQS) (38.0%) were the most common herbal formulas used. Huang-Qin (HQin) (44.6%), Yan-Hu-Suo (YHS) (40.5%), and Jie-Geng (JG) (39.5%) were the most commonly used single herbs. A CHM network analysis showed that JG was the core CHM in one cluster, and BM, MXSGT, and HQin were important CHMs in that cluster. In the other cluster, YHS was the core CHM, and SYGCT and JWXYS were important CHMs. ConclusionCHM as adjunctive therapy may reduce hyperlipidemia and the risk for cardiovascular disease in HIV-infected patients. The list of the comprehensive herbal medicines that the patients used might be useful in further scientific investigations or therapeutic interventions for preventing atherosclerosis among HIV-infected patients.

Platelet function and cardiovascular risk in adult HIV-infected patients on HAART: a protocol for a systematic review and meta-analysis

IntroductionThe incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected patients as compared with the general population. Although platelet activation and reactivity are implicated in the...

Prevalence of Elevated Blood Pressure in HIV-infected Children, Adolescents and Young Adults.

To the Editor: We read with interest the recently published article by Chatterton-Kirchmeier et al1 describing an increased prevalence of high blood pressure (HBP) in HIV-infected youths in the United States. Vertically, HIV-infected subjects appear to show excess risk of cardiovascular events, and we agree with the authors that prompt management of cardiovascular disease risk factors in this population is warranted, although it is frequently overlooked by pediatricians. The prevalence of hypertension reported by Chatterton-Kirchmeier et al,1 however, exceeds the data observed in other cohorts of HIV-infected youths and deserves comment. In 2011, our group enrolled 150 HIV-infected youths and 150 controls in a longitudinal follow-up cohort study addressing cardiovascular risk factors in Madrid.2 Mean age was 14.8 years (range, 2.5–24), and most were Caucasian vertically infected adolescents. Intima-media thickness (IMT), blood pressure (BP) and lipid and glycemic profiles were measured. After adjustment for sex, age and height, the median value of 3 BP measurements was used for diagnosis of hypertension. There was a 2.7% prevalence among HIV+, with no significant differences between HIV-infected and -uninfected controls. Nevertheless, IMT was increased in HIV-infected participants (0.43 vs. 0.42 mm, P = 0.001). Cardiovascular disease in HIV-infected patients might be related to accelerated atherosclerosis, most probably secondary to a series of factors, including direct viral effects, chronic inflammation, T-cell and monocyte activation and antiretroviral treatment-associated metabolic alterations.3 Although several studies have shown increased carotid IMT among HIV-infected children, reported BP values are typically similar to those observed in control subjects.2,4 Chatterton-Kirchmeier et al1 reported a prevalence of hypertension of 19.6% among 107 HIV-infected subjects 2–17 years old. These findings were based on a single BP measurement recorded in medical charts, adjusted for sex, age and height. Because repeated BP measurements in different occasions are widely recommended for the diagnosis of hypertension, we believe that these data must be interpreted very cautiously. Furthermore, the particular characteristics of this cohort might challenge the extrapolation of these findings to other populations. Almost 90% of the study participants were of African American ethnicity, a well-established risk factor for hypertension.5 Fifty-seven percent were male, and the prevalence of cardiovascular risk factors such as tobacco use or obesity (24% and 29%, respectively) was higher than in other cohorts.2,4 Overall, the incidence of past medical conditions associated with HBP was 17%. Exposure of this population to a greater burden of cardiovascular risk factors compared with what has been typically found in other HIV-infected populations is likely to confound the role of HIV infection as a determinant of hypertension. Besides, 33.8% of participants had acquired HIV horizontally, with a mean age of 17.8 years at recruitment, which necessarily implies a short-term exposure to the potential deleterious effects of HIV and antiretroviral treatment. Therefore, based on data from our group and others,1–4 we think that cardiovascular risk factors, and among them BP, should be aggressively sought in HIV-infected subjects, as prompt diagnosis and treatment of cardiovascular disease need to be optimized during infancy and adolescence in this population. In our view, however, the evidence supporting a direct relationship between HIV and HBP remains scarce. Talía Sainz, MD, PhD Department of Pediatrics, Tropical and Infectious Diseases Unit Hospital la Paz and, La Paz Research Institute (IdiPAZ) Sergio Serrano-Villar, MD, PhD Infectious Diseases Department, Hospital Universitario Ramón y Cajal and IRyCIS María José Mellado, MD, PhD Department of Pediatrics, Tropical and Infectious Diseases Unit Hospital la Paz and La Paz Research Institute (IdiPAZ), Madrid, Spain

Infectious and Non-infectious Etiologies of Cardiovascular Disease in Human Immunodeficiency Virus Infection.

Background: Increasing rates of HIV have been observed in women, African Americans, and Hispanics, particularly those residing in rural areas of the United States. Although cardiovascular (CV) complications in patients infected with human immunodeficiency virus (HIV) have significantly decreased following the introduction of antiretroviral therapy on a global scale, in many rural areas, residents face geographic, social, and cultural barriers that result in decreased access to care. Despite the advancements to combat the disease, many patients in these medically underserved areas are not linked to care, and fewer than half achieve viral suppression. Methods: Databases were systematically searched for peer-reviewed publications reporting infectious and non-infectious etiologies of cardiovascular disease in HIV-infected patients. Relevant articles cited in the retrieved publications were also reviewed for inclusion.Results: A variety of outcomes studies and literature reviews were included in the analysis. Relevant literature discussed the manifestations, diagnosis, treatment, and outcomes of infectious and non-infectious etiologies of cardiovascular disease in HIV-infected patients.Conclusion: In these medically underserved areas, it is vital that clinicians are knowledgeable in the manifestations, diagnosis, and treatment of CV complications in patients with untreated HIV. This review summarizes the epidemiology and causes of CV complications associated with untreated HIV and provide recommendations for management of these complications.

Neutrophil to Lymphocyte Ratio and Cardiovascular Disease Incidence in HIV-Infected Patients: A Population-Based Cohort Study.

Neutrophil to lymphocyte ratio (NLR) has been shown to predict occurrence of cardiovascular events in the general population. The aim of our study was to evaluate the role of NLR to predict major cardiovascular disease (CVD) events in HIV-infected subjects. We performed a retrospective cohort study of HIV-infected patients residing in the Local Health Authority (LHA) of Brescia, northern Italy, from 2000 to 2012. The incidence of CVD events in HIV-positive patients was compared with that expected in the general population living in the same area, computing standardized incidence ratios (SIRs). To evaluate the predictive role of NLR, univariate and multivariate Cox regression models were applied, computing hazard ratios (HRs). A total of 3766 HIV-infected patients (mean age 38.1 years, 71.3% males) were included (person-years 28768.6). A total of 134 CVD events occurred in 119 HIV-infected patients. A 2-fold increased risk (SIR 2.02) of CVD was found in HIV-infected patients compared to the general population. NLR levels measured at baseline and during follow-up were independently associated with CVD incidence, when also adjusting for both traditional CVD risk factors and HIV-related factors (HR 3.05 for NLR≥ 1.2). The area under the receiver operating characteristics (ROC) curve showed a modest, not statistically significant, increase, from 0.81 to 0.83, with addition of NLR to Framingham risk score model covariates. In conclusion an elevated NLR is a predictor of risk CVD in HIV-infected patients, independently from the traditional CVD risk factors.

Nitric oxide levels in HIV-infected, untreated patients and HIV-infected patients receiving antiretroviral therapy.

The role of nitric oxide (NO) in HIV infection is ambiguous; controversy exists around whether the levels of serum NO are increased or decreased in HIV-infected patients. Thus, it is necessary to reassess NO levels in HIV-infected patients. The aim of this study was to investigate the nitrite/nitrate metabolite (NOx) levels in HIV-infected untreated patients and in HIV-infected patients receiving highly active antiretroviral therapy (HAART), compared with HIV-uninfected individuals (control group). The HIV-infected patients enrolled in this study had been receiving HAART for at least 6 months (HIV-treated) or had not received HAART for at least 6 months (HIV-untreated group). New recommendations encourage initiating treatment in HIV-infected adults at a CD4 cell count of 500 cells/mm(3) or less. We also investigated whether levels of NOx were associated with immunophenotypic characteristic of HIV-infected patients. Our results showed a statistically significant increase in NOx levels in the HIV-untreated group (164.0 ± 166.6 μmol/L), compared with both the control (98.9 ± 59.4 μmol/L) and HIV-treated group (71.7 ± 53.3 μmol/L). Multiple regression analysis showed that the differences in NOx level were independent of gender, liver enzyme level, lipid measurement, and hematological parameters. In addition, a lower CD4/CD8 ratio was associated with higher NOx levels in HIV-infected patients. The results further revealed that NOx levels were increased in HIV infection, and that derangement of immune system function was associated with increased NO levels. The levels of NOx were found to decline with the use of HAART, which may contribute to cardiovascular disease in HIV-infected patients.

Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.

Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.

Epidemiology and management of antiretroviral-associated cardiovascular disease.

Risk and manifestations of cardiovascular disease (CVD) in patients infected with human immunodeficiency virus (HIV) will continue to evolve as improved treatments and life expectancy of these patients increases. Although initiation of antiretroviral (ARV) therapy has been shown to reduce this risk, some ARV medications may induce metabolic abnormalities, further compounding the risk of CVD. In this patient population, both pharmacologic and nonpharmacologic strategies should be employed to treat and reduce further risk of CVD. This review summarizes epidemiology data of the risk factors and development of CVD in HIV and provides recommendations to manage CVD in HIV-infected patients.

GW25-e4539 Prevention of Cardiovascular Disease in HIV-Infected Patients

World Health Organization (WHO) estimates that cardiovascular disease (CVD) and human immunodeficiency virus (HIV) will top the causes for global mortality and disability in 2030. How to develop and implement effective primary prevention strategy in HIV-infected patients with high cardiovascular

Heart failure in HIV infection

Since the advent of highly active antiretroviral treatment, accelerated atherosclerosis resulting in coronary artery disease (CAD) has become an area of increasing concern among patients infected with HIV. As CAD has replaced myocarditis and opportunistic infection as the most common cause of heart failure in this population, it is necessary to re-evaluate the specific risks of cardiovascular disease in HIV-infected patients taking into consideration the processes driving atherogenesis. Recent data illustrating that atazanavir is not associated with an increased risk of CAD argue against a class-wide association of protease inhibitors in HIV treatment and adverse cardiovascular outcomes. C-C chemokine receptor-type 5 has been identified as a potential target for pharmacological therapy to manage the process of atherosclerosis while simultaneously having an antiretroviral effect. Additionally, as the use of statins has recently been associated with new-onset diabetes in the general population, further investigation of this risk in HIV-infected patients is necessary. HIV-infected patients have an increased risk of CAD and subsequently heart failure. This is likely because of a confluence of several factors including: conventional risk factors, HIV-specific processes driving inflammation, coagulatory pathway and endothelial dysfunction. The benefits of antiretroviral drugs in terms of overall survival rates outweigh the risks of dyslipidemia. The focus of the management of cardiovascular risk remains in the domains of primary and secondary prevention. More accurate risk stratification, which accounts for HIV-specific risk factors, is now increasingly warranted.

HIV Infection and Cardiovascular Disease

HIV Infection and Cardiovascular Disease

Screening and management of cardiovascular disease in Australian adults with HIV infection

Cardiovascular disease (CVD) is common in HIV infection. With no specific Australian guidelines for the screening and management of CVD in HIV-infected patients, best clinical practice is based on data from the general population. We evaluated adherence to these recommendations by primary care physicians who treat HIV-infected patients. Primary care physicians with a special interest in HIV infection were asked to complete details for at least 10 consecutive patient encounters using structured online forms. This included management practices pertaining to blood pressure (BP), blood glucose, electrocardiogram, lipid profile and CVD risk calculations. We assessed overall adherence to screening and follow-up recommendations as suggested by national and international guidelines. Between May 2009 and March 2010, 43 physicians from 25 centres completed reporting for 530 HIV-infected patients, of whom 93% were male, 25% were aged 41-50 years and 83% were treated with antiretrovirals. Risk factors for CVD were common and included smoking (38%), hyperlipidaemia (16%) and hypertension (28%). In men aged >40 years and women aged >50 years without evidence of ischaemic heart disease, only 14% received a CVD risk assessment. Lipid and BP assessments were performed in 87% and 88% of patients, respectively. This Australian audit provides unique information on the characteristics and management of HIV and CVD in clinical practice. We have found a high burden of risk for CVD in HIV-infected Australians, but current screening and management practices in these patients fall short of contemporary guidelines.

Prevalence of cardiovascular diseases in HIV-infected outpatients: results from a prospective, multicenter cohort study

Recent studies suggest a rising rate of cardiovascular disease (CVD) in HIV-infected subjects. Although most countries have an aging HIV-infected population, there remains a lack of knowledge about associated cardiovascular diseases. This ongoing prospective multicentre observational cohort study aims to elucidate CVD prevalence in HIV-infected outpatients by standardized non-invasive cardiovascular screening. Cardiovascular and coronary risk was calculated using Framingham risk scores. 803 HIV-infected subjects (mean age 44.2years, female 16.6%) were included. The prevalence of CVD in HIV-infected subjects was 10.1% (95% CI 8.0-12.2%). Aging HIV-infected patients (≥45years, N=348) exhibited significantly increased rates of CVD, including an elevated frequency of coronary artery disease (7.5 vs. 1.8%, p<0.001), myocardial infarction (6.0 vs. 1.8%, p=0.002) and peripheral arterial diseases (4.6 vs. 1.5%, p<0.017). Furthermore, aging patients exhibited a higher rate of chronic heart failure (5.2 vs. 1.5%, p<0.001), predominantly of ischemic etiology. In multivariate analyses, age (OR 2.05 per decade, 95% CI 1.64-2.56), smoking (OR 5.96 per decade, 95% CI 2.31-15.38) and advanced symptomatic HIV infection (OR 2.60 per decade, 95% CI 1.31-5.15), were significantly associated with the prevalence of CVD. Based on the 10-year cardiovascular risk estimation, a disproportionate increase in cardiac events has to be expected in aging HIV-infected subjects in the next decades (≥45years/<45years 16.4 vs. 4.2%, p<0.001). CVD in aging HIV-infected population is an increasing medical challenge. In the era of antiretroviral therapy, prevention and diagnostic strategies are essential to reduce the prevalence of CVD in HIV-infected patients.

Electrocardiographic Spatial QRS-T Angle and Incident Cardiovascular Disease in HIV-Infected Patients (from the Strategies for the Management of Antiretroviral Therapy [SMART] Study)

Widening of the electrocardiographic (ECG) spatial QRS-T angle has been predictive of cardiovascular disease (CVD) events in the general population. However, its prognostic significance in human immunodeficiency virus (HIV)-infected patients remains unknown. The spatial QRS-T angle was derived from the baseline resting 12-lead electrocardiogram of 4,453 HIV-infected patients aged 43.5 ± 9.3 years from the Strategies for Management of Antiretroviral Therapy (SMART) trial. CVD events were identified during a median follow-up of 28.7 months. Quartiles of the spatial QRS-T angle was calculated for men and women separately, and values in the upper quartile were considered as a widened angle (values >74° for women and >93° for men). A multivariate Cox proportional hazards analysis was used to examine the association between a widened baseline spatial QRS-T angle and incident CVD events. During 11,965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events/100 person-years. The rate of CVD events in those with a widened spatial QRS-T angle was almost double the rate in those with a normal spatial QRS-T angle (rate ratio 1.94, 95% confidence interval 1.40 to 2.69; p <0.001). In a model adjusted for study treatment arm, demographics, CVD risk factors, HIV characteristics, inflammatory markers, and other ECG abnormalities, a widened spatial QRS-T angle was associated with a >50% increased risk of CVD events compared to a normal spatial QRS-T angle (hazard ratio 1.53, 95% confidence interval 1.07 to 2.17; p = 0.02). No interaction was seen by SMART trial arm (p value for interaction = 0.37) or gender (p value for interaction = 0.84). In conclusion, a widened spatial QRS-T angle was independently predictive of CVD events in HIV-infected patients receiving antiretroviral therapy. This highlights the potential role of routine electrocardiography as a simple noninvasive CVD risk-screening tool in HIV-infected patients.

Worsening Endothelial Function with Efavirenz Compared to Protease Inhibitors: A 12-Month Prospective Study

ObjectiveChanges in endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery, has not been systematically assessed beyond 6 months of initiation of antiretroviral therapy (ART) when drug-related effects might offset initial improvements with virologic control.DesignWe assessed 6 and 12 month changes in FMD [presented as median (quartile 1, quartile 3)] and circulating HIV and cardiovascular biomarkers in 23 subjects initiating ART.ResultsThere were no significant changes in FMD at 6 or 12 months overall despite significant increases in CD4 cell count and HDL-C and reductions in HIV RNA level, MCP-1, IP-10, sVCAM-1, sTNFR2, and sCD14. However, there were significant differences (P = 0.04) in the changes in FMD between those receiving efavirenz [N = 12; −3.50% (−4.90%, 0.68%)] vs. protease inhibitors at 12 months [N = 11; 1.50% (−0.86%, 4.56%)]. The differences in changes in FMD between those receiving and not receiving emtricitabine/tenofovir/efavirenz were more pronounced and were significantly different at both 6 and 12 months (P<0.02 for both). Additional studies showed no significant differences in changes in 25-(OH)-vitamin D, PTH, FGF-23, of F2-isoprostane levels between efavirenz and PI use or between those receiving and not receiving emtricitabine/tenofovir/efavirenz.ConclusionEfavirenz use was associated with reduced FMD at 12 months compared to PI-based regimens while emtricitabine/tenofovir/efavirenz was associated with reduced FMD at both 6 and 12 months compared to those not receiving this combination. Long-term effects of antiretrovirals on endothelial function may play an important role in the risk of cardiovascular disease in HIV-infected patients.