Short communication: effects of omega-3 fatty acids on triglycerides and high-density lipoprotein subprofiles in HIV-infected persons with hypertriglyceridemia.

Hypertriglyceridemia and low high-density lipoprotein (HDL)-cholesterol (HDL-C) may contribute to a presumed accelerated risk for cardiovascular disease in HIV-infected individuals. We evaluated the effect of omega-3 fatty acid treatment on triglycerides, low-density lipoprotein (LDL)-C, HDL-C, and HDL subpopulations. Forty-one HIV-seropositive subjects with hypertriglyceridemia (≥150 mg/dl) on active antiretroviral therapy were enrolled in this placebo-controlled, double-blind, randomized, crossover trial comparing the effects of omega-3 fatty acid treatment (1.9 g EPA and 1.5 g DHA) on triglycerides, LDL-C, HDL-C, and HDL subpopulations. An independent sample t-test was used to assess the study start to posttreatment change for all components. After omega-3 fatty acid treatment, triglyceride levels decreased 63.2±86.9 mg/dl (p<0.001). No significant changes in total cholesterol, LDL-C, or HDL-C were found. Within HDL subpopulations, significant changes were seen in the most atheroprotective HDL particles, α-1, which increased by 2.5±5.6 mg/dl (p<0.05), and preα-1, which increased by 0.6±1.0 mg/dl (p<0.001). Preα-3, a presumably atherogenic HDL particle, decreased by 0.5±0.9 mg/dl (p<0.01). Omega-3 fatty acid treatment significantly lowered triglyceride levels in HIV-positive patients with moderate hypertriglyceridemia. While no study-wide improvements in LDL-C or HDL-C were detected, the HDL subpopulation profile changed in a beneficial way suggesting more cardioprotection after treatment.

HIV infection and progression of carotid and coronary atherosclerosis: the CARE study.

BACKGROUND: Progression of carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) are increasingly used as surrogates for vascular risk. We assessed the predictors of c-IMT and CAC progression in a large longitudinal cohort of HIV-infected adults. METHODS: c-IMT, CAC scores, and vascular and HIV risk factors were evaluated at baseline and at 3-year follow-up in 255 HIV-infected adults. Multivariate regression was used to determine the predictors of atherosclerotic progression. RESULTS: The mean change in c-IMT per year of follow-up was 0.016 mm for the common and 0.020 mm for the internal. Significant predictors of yearly progression were age, systolic blood pressure, triglycerides, and insulin for common c-IMT and triglycerides >=150 mg/dL, glucose >126 mg/dL, use of glucose-lowering medications, quantitative insulin sensitivity check index, high waist circumference, and current smoking for internal c-IMT. Twenty-eight percent had CAC progression. Of those with zero CAC at baseline, 32% had detectable scores at follow-up. Of those with detectable CAC at baseline, 26% had progression at follow-up. For CAC score, quantitative insulin sensitivity check index, apolipoprotein B, and triglycerides predicted progression. Those with abnormal surrogate markers at baseline were more likely to have the metabolic syndrome reversed and be started on antihypertensive medications over the 3-year follow-up period than those who had no abnormalities at baseline. CONCLUSIONS: Although c-IMT and CAC progression rates in HIV-infected patients appear higher than expected for this age and risk groups, traditional cardiovascular risk factors remain the strongest determinants of carotid and coronary atherosclerotic disease progression in HIV-infected patients. Aggressive cardiovascular risk reduction is effective at slowing the atherosclerotic progression in those with preexisting disease.

Markers of atherosclerosis and inflammation and mortality in patients with HIV infection.

OBJECTIVE: HIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. Surrogate marker studies suggest an increased prevalence of vascular abnormalities in HIV infection. We examined the association of all-cause mortality in HIV-infected patients with carotid artery intima-media thickness (cIMT) and high-sensitivity C-reactive protein (hsCRP). DESIGN AND METHODS: Baseline risk factors, cIMT and hsCRP were prospectively measured in 327 HIV-infected participants. Follow-up time with median of 3.1 years was calculated from baseline to death or censored dated 7/31/07. Cox Proportional Hazards models were used to study risk factors associated with mortality. RESULTS: Thirty-eight (11.6%) of participants have died since study enrollment. cIMT was significantly higher in those who died and decedents were significantly more likely to have cIMT above the 75th percentile. Those who died had higher hsCRP than those alive and more had hsCRP values above 3mg/L. CD4 count was lower and log(10) viral load was higher in decedents, but antiretroviral regimens were similar in both groups. cIMT and hsCRP levels were significantly associated with mortality (HR = 2.74, 95% CI 1.26-5.97, p = 0.01; HR = 2.38, 95% CI 1.15-4.9, p = 0.02). CONCLUSIONS: Our study demonstrated a strong association of carotid IMT and hsCRP with all-cause death in this HIV-infected population despite being similar with respect to exposure to antiretroviral medications. Together these surrogate markers may be indices of chronic inflammation and unfavorable outcomes in HIV-positive patients.

Metabolic syndrome and subclinical atherosclerosis in patients infected with HIV.

BACKGROUND: The present study examines the association between carotid and coronary atherosclerosis and metabolic syndrome in human immunodeficiency virus (HIV)-infected adults. METHODS: We measured the common and internal carotid intima-media thickness (c-IMT) using B-mode ultrasonography, and we measured coronary artery calcium (CAC) using high-resolution, electrocardiographic, synchronized, computed tomography, for 314 HIV-infected men and women. Metabolic syndrome was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. We compared the c-IMT measurements and CAC scores of patients with metabolic syndrome with the scores of those without metabolic syndrome using a Wilcoxon test for continuous variables and a chi2 test for categorical variables. To examine the association between surrogate markers and metabolic syndrome, we used logistic regression analysis. RESULTS: Participants with metabolic syndrome were more likely to have a common c-IMT measurement >0.8 mm than were those without metabolic syndrome (17% vs.7%; P=.009), but both groups were equally likely to have an internal c-IMT measurement >1.0 mm (20% vs. 13%; P=.15). Any positive CAC score was more likely to occur for participants with metabolic syndrome (80.3% vs. 46.7%; P<.0001). In a multivariate model adjusted for sex, age, ethnicity, and smoking status, participants with metabolic syndrome were more likely than those without metabolic syndrome to have an abnormal common c-IMT measurement (odds ratio [OR], 2.9; P=.020) and detectable CAC scores (OR, 4.9; P<.0001) but not a higher internal c-IMT measurement (OR, 1.6; P=.255). CONCLUSION: Our study demonstrates that HIV-infected individuals with metabolic syndrome may be at increased risk for subclinical atherosclerosis and supports screening for metabolic syndrome among HIV-infected patients at risk for cardiovascular disease.

Risk of cardiovascular disease in a cohort of HIV-infected adults: a study using carotid intima-media thickness and coronary artery calcium score.

BACKGROUND: There is concern that human immunodeficiency virus (HIV) infection and the use of highly active antiretroviral therapy lead to accelerated atherosclerosis and increased risk of cardiovascular disease. We measured 2 surrogate markers of subclinical atherosclerosis, carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) scores, in HIV-infected adults. METHODS: A cross-sectional analysis of 242 men and 85 women with HIV infection was used. Carotid ultrasonography and coronary computed tomography were performed, and their associations with cardiovascular risk factors were examined. RESULTS: Among men, the mean (+/- standard deviation [SD]) common c-IMT was 0.62+/-0.2 mm, the mean (+/-SD) internal c-IMT was 0.76+/-0.5 mm, and 136 patients (56.1%) had detectable CAC. Among women, the mean (+/-SD) common c-IMT was 0.59+/-0.2 mm, the mean (+/-SD) internal c-IMT was 0.66+/-0.4 mm, and 40 patients (47.1%) had detectable CAC. Neither the c-IMT nor the CAC score differed by antiretroviral therapy class or individual medications for either sex. For men, age and waist circumference independently predicted common c-IMT; age, systolic blood pressure, and high-sensitivity C-reactive protein level independently predicted internal c-IMT; and age, apolipoprotein B level, and high-sensitivity C-reactive protein level independently predicted CAC score. For women, age and body mass index independently predicted common c-IMT; age independently predicted internal c-IMT; and age and glucose level independently predicted CAC score. CONCLUSIONS: Our participants had more abnormal surrogate markers than expected at a relatively young age, but those were not associated with use of highly active antiretroviral therapy or protease inhibitors. At present, the positive associations were primarily with traditional and novel cardiovascular risk factors. Some HIV-specific (not treatment-specific) factors were observed; they may become more evident with prolonged HIV infection and treatment.

Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients.

OBJECTIVE: To study the effects of HIV-infection and protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) on the lipid and high-density lipoprotein (HDL) subpopulation profile and to relate the changes to coronary heart disease (CHD)-risk. METHODS AND DESIGN: The lipid and HDL subpopulation profiles of HIV-positive subjects (n = 48) were studied prospectively by comparing pre- and post-PI-HAART data as well as cross-section by comparing the profiles to HIV-negative subjects with (n = 96) and without CHD (n = 96). RESULTS: HIV-infected HAART-naïve subjects had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and HDL-C and higher concentration of triglycerides (TG) than healthy controls. After receiving PI-based HAART, LDL-C and TG concentrations increased, while HDL-C concentrations remained unchanged. The HDL subpopulation profiles of HAART-naïve HIV-positive patients were significantly different from those of healthy controls and were similar to those with CHD. Moreover, the HDL subpopulation profile changed unfavorably after PI-based HAART, marked with increased concentrations of the small, lipid-poor pre-beta-1 HDL (32% or 3.9 mg/dl; p < 0.001), and decreased concentration of the large, cholesterol-rich alpha-1 HDL (9% or 1 mg/dl ns). CONCLUSION: An already unfavorable lipid and HDL subpopulation profile of HIV-positive HAART-naïve subjects further deteriorated after receiving PI-based treatment, which may cause increased CHD-risk in these subjects.

Alterations in lipid profiles in HIV-infected patients treated with protease inhibitor therapy are not influenced by diet.

BACKGROUND: The use of protease inhibitor (PI) -based highly active antiretroviral therapy (HAART) in patients infected with human immunodeficiency virus (HIV) has been linked to alterations in lipid profiles. METHODS: Longitudinal cohort study. Lipid profiles were evaluated pre- and post-PI therapy in 49 HIV-infected patients. Diet was also evaluated to determine any contribution to alterations in lipid levels. RESULTS: Pre- and post-PI-based HAART samples were examined from 42 men and 7 women, mean age 40.6 years. Mean CD4 count pre-PI was 242 +/- 205 cells/mm(3); HIV RNA was 4.2 log(10) copies/mL; body mass index (BMI) was 24.7 +/- 3.6 kg/m(2); body fat was 17.1 +/- 9.1 kg by bioelectrical impedance analysis (BIA), dietary intake was 2654 +/- 732 kcal/day. Post-PI samples were collected 5.7 +/- 1.66 months after starting therapy. CD4 counts increased to 384 +/- 323 cells/mm(3) and RNA decreased 1 log post-PI. Post-PI BMI (25.2 kg/m2), percent body fat (17.4%) and caloric intake (2656 kcal/day) were unchanged. Pre-PI total cholesterol (TC) in men was 167.6 +/- 42.4 mg/dL; TC increased (190.4 +/- 47.9 mg/dL) post-PI (p < .0001). Pre-PI triglycerides (TG) were 154.5 +/- 109.4 mg/dL; TG increased post-PI (266.1 +/- 363.6 mg/dL, p < .03). Low-density lipoprotein (LDL) -C was 97.8 +/- 31 mg/dL pre-PI and rose to 107.1 +/- 34.7 mg/dL post-PI (p < .05). High density lipoproteins (HDLs) were below desired levels before initiation of PI therapy and remained low. CONCLUSIONS: PI therapy significantly alters lipid profiles in HIV-infected patients. Dietary intake did not contribute to changes in lipid profile. More longitudinal studies are needed to demonstrate whether these alterations contribute to additional cardiovascular risk.

Nutrition assessment in HIV infection.

Nutrition assessment is a vital component of the general care of HIV-infected adults. With access to highly active antiretroviral therapy (HAART), HIV infection may become a chronic, manageable disease. Nutritional and metabolic complications traditionally associated with HIV infection such as hypertriglyceridemia, low levels of high-density lipoprotein (HDL) cholesterol, and weight loss continue to occur. However, emerging abnormalities such as regional alterations in body shape (fat re-distribution syndrome or HIV-associated lipodystrophy), increasing body weight, high levels of low-density lipoprotein (LDL) cholesterol, insulin resistance, and other metabolic derangements may also be present. In addition, as patients are living longer, they may be susceptible to other age-related diseases such as diabetes, cardiovascular disease, and obesity. In this article, we review strategies for nutrition assessment and management in HIV-infected adults. Attention is focused on specific symptoms such as weight loss and diarrhea and specific disorders such as lipodystrophy, micronutrient deficiencies, and dyslipidemia, which commonly affect HIV-infected individuals. Proper attention to nutritional status may help to reduce the burden of disease and promote an enhanced quality of life in HIV-infected individuals.

Comparing megestrol acetate therapy with oxandrolone therapy for HIV-related weight loss: similar results in 2 months.

Weight loss is known to impact survival among patients infected with human immunodeficiency virus (HIV) even in the era of highly active antiretroviral therapy (HAART). In a randomized trial, we compared the effects of 2 months of treatment with either megestrol acetate (800 mg every day) or oxandrolone (10 mg twice per day) on body weight and composition in patients with weight loss of > or =5 kg who were receiving HAART. The mean weight was 66 kg, and the mean body mass index was 21. Mean weight gain in the megestrol acetate and the oxandrolone arms were 2.8 kg (4.6% of the baseline value) and 2.5 kg (3.9% of the baseline value), respectively (P=.80). Lean body mass accounted for 39% of weight gain in the megestrol acetate arm and 56% in the oxandrolone arm (P=.38). Seven patients in the megestrol acetate arm and 5 patients in the oxandrolone arm reported minor adverse events (P=.74). In conclusion, megestrol acetate therapy and oxandrolone therapy have similar effects on body weight and composition and are safe and well-tolerated during HAART.

Combination megestrol acetate, oxandrolone, and dietary advice restores weight in human immunodeficiency virus.

BACKGROUND: We examined changes in total body weight (TBW) and health-related quality of life (HRQL) during prolonged combination weight-gaining therapy and dietary advice in HIV. DESIGN: This was a cohort study of patients initially randomized to single agent therapy for 2 months, megestrol acetate (800 mg daily), or oxandrolone (10 mg twice daily), followed by both agents and dietary advice for 5 months. METHODS: Two community health clinics and 1 urban infectious disease clinic were included, as were HIV-positive adult patients receiving highly active antiretroviral therapy with documented 5% weight loss. TBW and HRQL were measured after 7 months (7 m). RESULTS: Twenty-nine of 39 participants completed 7 m. The average sample age was 40 years, 75% were male, and 52% were of color at enrollment. Baseline mean TBW and body mass index (BMI) were 62.5 kg and 21 kg/m(2), respectively. Net gains in TBW, lean body mass, and fat during the 7 m were 5.3 kg (8.5% of baseline), 2.1 kg, and 3.1 kg, respectively (p < .01 for each). BMI increased to 23.1 kg/m(2) (p < .01). Dietary intake increased by 467 kcal/day (p = .03). Physical health improved by 5.7 (100-point scale, p < .01), and mental health was unchanged (-4.2, p = .11). In multivariable models, female gender (p < .01), lower baseline HIV viral load (p = .03), and increasing age (p < .01) were associated with TBW gain. Injection drug use (p < .01) and higher baseline HIV viral load (p < .01) were associated with reduction in physical health. CONCLUSIONS: Prolonged combination therapy with megestrol acetate, oxandrolone, and dietary advice could reverse weight loss and low BMI associated with incomplete viral suppression and improve physical health.