Sally Skinner

Incidence of metabolic syndrome in a cohort of HIV-infected adults and prevalence relative to the US population (National Health and Nutrition Examination Survey).

Background:Metabolic syndrome increases the risk of cardiovascular outcomes and type II diabetes. Most of the metabolic abnormalities defining metabolic syndrome are observed in HIV. Objective:To determine the incidence and risk factors for metabolic syndrome in HIV-infected adults in the Nutrition for Healthy Living (NFHL) study (2000-2003) and prevalence relative to the findings of the National Health and Nutrition Examination Survey (NHANES) (1999-2002). Methods:Metabolic syndrome is ≥3 of the following: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hypertension, abdominal obesity, and high serum glucose. The baseline prevalence of metabolic syndrome in the NFHL study (n = 477) was compared to that in the NHANES (n = 1876), adjusted for age, race, gender, poverty, exercise, and diet. Results:Almost one quarter of NFHL subjects had metabolic syndrome. Most with metabolic syndrome (77%) had low HDL and hypertriglyceridemia plus ≥1 additional abnormality. The prevalence of metabolic syndrome was significantly lower in HAART and non-HAART users compared with NHANES participants unadjusted for body mass index (BMI). After adjustment for BMI, it was no longer significant but the trend remained. The incidence of metabolic syndrome in the NFHL study was higher with increasing viral load, higher BMI, higher trunk-to-limb fat ratio, and Kaletra (lopinavir/ritonavir) or didanosine (ddI) use and lower among college-educated persons. Conclusions:Metabolic syndrome is mostly diagnosed through low HDL and high triglycerides in HIV. The risk of developing the syndrome is related to HIV, specific medications, and body fat.

Prevalence of, Evolution of, and Risk Factors for Fat Atrophy and Fat Deposition in a Cohort of HIV-Infected Men and Women

BACKGROUND At present, no uniform definition of human immunodeficiency virus (HIV)-associated lipoatrophy exists. The risk factors for fat atrophy (FA) and central fat deposition (FD) are multifactorial. We assessed the evolution and predictors of FA and FD in HIV-infected men and women. METHODS Participants (n = 452) were evaluated at baseline (starting in November 1998) and 1 year later. FA was defined as triceps skin-fold measurement less than the 10th percentile on the National Health and Nutrition Examination Survey for sex and age. FD was defined as a waist-to-hip ratio of > 0.95 for men and of > 0.85 for women. Predictors of the baseline prevalence of FA and FD and new cases of each syndrome after 1 year were determined. RESULTS The baseline prevalences of FA, FD, and combined FA and FD were 35%, 44%, and 14%, respectively. Twenty-two percent of subjects had newly developed FA at 1 year, and 16% of subjects with FA at baseline did not have it at 1 year. Also, 23% of subjects had newly developed FD at 1 year, and 15% of those with FD at baseline did not have it at 1 year. The risk of developing new FA was increased among participants with low triceps skin-fold values (P < .001), smaller hips (P < .001), higher nadir HIV load (P = .006), abacavir use (P < .001), stavudine use (P < .001), and use of highly active antiretroviral therapy (P = .002). The risk of developing new FD was higher among women (P < .001) and among participants with greater body fat levels (P = .005) and higher triglyceride levels (P < .001), and it was lower among those with a high school education (P = .003) and higher triceps skin-fold values (P = .026). CONCLUSIONS FA and FD are common in HIV-infected patients, but may change over time in the individual. FA and FD appear to be different syndromes, because risk factors for the development differ, and the prevalence of the combined syndrome differs from the prevalences of the 2 independent syndromes.

Poverty, Hunger, Education, and Residential Status Impact Survival in HIV

Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.

CD4+ Cell Count, Viral Load, and Highly Active Antiretroviral Therapy Use Are Independent Predictors of Body Composition Alterations in HIV-Infected Adults: A Longitudinal Study

BACKGROUND To understand the concurrent effects of human immunodeficiency virus (HIV) infection, the immune system, and antiretroviral therapy on body composition alterations, we examined annualized composition changes in HIV-infected adults who were receiving stable antiretroviral therapy. METHODS With use of data from the Nutrition For Healthy Living Study, we performed multivariate analyses using longitudinal models to evaluate the relationship of CD4+ cell count, viral load, and highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART) with changes in trunk and extremity composition for 110 men and 42 women who provided data relating to 194 study intervals (i.e., intervals of time between 2 assessment visits). Of these intervals, 165 involved HAART use (89.7% involved protease inhibitor-based regimens), and 29 did not involve HAART use. Patients receiving HAART or ART (who had continuous use during the interval) were compared with HAART- or ART-naive subjects. RESULTS The median length of intervals between visits was 12.9 months (interquartile range, 12.1-17.6 months). In models adjusted for HAART or ART use, baseline CD4+ cell count was positively associated with increased trunk fat (mean increase per year, 2.3% per 100 cells/mm3; 95% confidence interval [CI], 0.7%-3.9%]) and, in men, with increased extremity fat (mean increase per year, 1.8% per 100 cells/mm3; 95% CI, 0.6%-3.0%). Increase in CD4+ cell count predicted increased extremity lean mass (mean increase per year, 0.6% per 100 cells/mm3; 95% CI, 0.05%-1.1%). Higher baseline viral load predicted fat loss (trunk fat loss per year, -5.0% per log10 copies/mL; 95% CI, -9.4% to -0.7%; extremity fat loss per year, -3.4% per log10 copies/mL; 95% CI, -6.1% to -0.6%), as did zidovudine use (trunk fat loss per year, -10.8%; 95% CI, -20.4% to -1.4%; extremity fat loss per year, -4.9%; 95% CI, -9.8% to -0.01%). HAART use independently predicted decreased bone mineral content (extremity bone mineral content loss per year, -1.6%; 95% CI, -3.1% to -0.08%) but did not predict changes in fat or lean mass. Receipt of protease inhibitor-based HAART predicted a -1.9% decrease in extremity bone mineral content per year (95% CI, -3.6% to -0.2%), and zidovudine use predicted a -2.6% decrease in trunk bone mineral content per year (95% CI, -4.4% to -0.8%). CONCLUSIONS Baseline viral load, CD4+ cell count, and change in CD4+ cell count predicted alterations in trunk fat, extremity fat, and lean mass. HAART use and zidovudine use were associated with bone loss, and zidovudine use was associated with fat loss, but HAART use was not associated with fat mass changes.

Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

BACKGROUND Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Repeated assessments of food security predict CD4 change in the setting of antiretroviral therapy

Food insecurity is highly prevalent in HIV-infected populations, and analyses utilizing multiple assessments of food security to predict CD4 change are lacking. Five hundred Ninety-two patients with ≥ 4 food security assessments were followed prospectively. In the final model, for patients using antiretroviral therapy, increases in CD4 counts were on average 99.5 cells less for individuals with at least 1 episode of food insecurity compared with those consistently food secure (P < 0.001). Other sociodemographic factors were not predictive. Repeated assessments of food security are potent predictors of treatment response notwithstanding antiretroviral therapy use. Potential mechanisms for this association are proposed.

Increasing Infectious Endocarditis Admissions Among Young People Who Inject Drugs

People who inject drugs (PWID) are at risk for infective endocarditis (IE). Hospitalization rates related to misuse of prescription opioids and heroin have increased in recent years, but there are no recent investigations into rates of hospitalizations from injection drug use-related IE (IDU-IE). Using the Health Care and Utilization Project National Inpatient Sample (HCUP-NIS) dataset, we found that the proportion of IE hospitalizations from IDU-IE increased from 7% to 12.1% between 2000 and 2013. Over this time period, we detected a significant increase in the percentages of IDU-IE hospitalizations among 15- to 34-year-olds (27.1%–42.0%; P < .001) and among whites (40.2%–68.9%; P < .001). Female gender was less common when examining all the IDU-IE (40.9%), but it was more common in the 15- to 34-year-old age group (53%). Our findings suggest that the demographics of inpatients hospitalized with IDU-IE are shifting to reflect younger PWID who are more likely to be white and female than previously reported. Future studies to investigate risk behaviors associated with IDU-IE and targeted harm reduction strategies are needed to avoid further increases in morbidity and mortality in this rapidly growing population of young PWID.

Progression of carotid intima-media thickness and coronary artery calcium over 6 years in an HIV-infected cohort.

Objective:To evaluate changes in cardiovascular disease risk surrogate markers in a longitudinal cohort of HIV-infected adults over 6 years. Design:Internal carotid artery (ICA) and common carotid artery (CCA) intima-media thickness (IMT), coronary artery calcium (CAC), vascular, and HIV risk factors were prospectively examined over 6 years in HIV-infected adults from 2002 to 2010. Setting:Longitudinal cohort study with participants from urban center and surrounding communities. Subjects/Participants:Three hundred forty-five HIV-infected participants were recruited from a longitudinal cohort study. Two hundred eleven participants completed the study and were included in this analysis. Main Outcome Measures:Total and yearly ICA and CCA IMT change; CAC score progression. Results:Participants were 27% female and 49% nonwhite; mean age at start was 45 ± 7 years. The median change in ICA and CCA over 6 years was 0.15 mm (0.08, 0.28) and 0.12 mm (0.09, 0.15), respectively. Age, baseline triglycerides ≥150 mg/dL, and pack-years smoking were associated with ICA IMT change; age, cholesterol, nadir CD4+ count, and protease inhibitor use were associated with CCA IMT change. Diabetes, HIV viral load, and highly active antiretroviral therapy duration were associated with CAC progression. Conclusions:Carotid IMT and CAC progressed in this HIV-infected cohort. Some HIV-specific characteristics were associated with surrogate marker changes, but the majority of risk factors continue to be traditional. Aggressive identification and management of modifiable risk factors may reduce progression of cardiovascular disease risk in this population.

Framingham risk score and early markers of atherosclerosis in a cohort of adults infected with HIV.

BACKGROUND The utility of the Framingham risk score among individuals infected with HIV is poorly understood. We examined the association of Framingham risk scores with surrogate markers of atherosclerosis in a carefully characterized cohort of adults infected with HIV. METHODS We calculated Framingham risk scores and measured carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) scores in 334 participants from the Nutrition for Healthy Living study. Cardiovascular risk factors, c-IMT and CAC scores were assessed for each Framingham risk subgroup (low versus intermediate/high risk). We used adjusted and unadjusted linear and logistic regression to examine the association between clinical factors and Framingham risk group with c-IMT and CAC scores. RESULTS Patients with intermediate/high Framingham risk scores were more likely to have internal c-IMT ≥ 1.0 mm (26% versus 12%; P=0.003) and common c-IMT ≥ 0.8 mm (22% versus 5%; P < 0.001). These patients were also more likely to have detectable CAC (78% versus 48%; P < 0.001). Intermediate/high Framingham risk scores were significantly associated with internal c-IMT ≥ 1.0 mm (odds ratio 2.65 [95% confidence interval 1.37-5.13]) and common c-IMT ≥ 0.8 mm (odds ratio 5.24 [95% confidence interval 2.39-11.50]). Intermediate/high Framingham risk scores were also significantly associated with detectable CAC (odds ratio 3.84 [95% confidence interval 2.05-7.16]). The addition of HIV-related variables did not improve the accuracy of the Framingham risk score. CONCLUSIONS Our study shows that increased Framingham risk scores are associated with abnormal early and late surrogate markers of atherosclerosis in adults infected with HIV, and might predict the risk of cardiovascular complications in this population.

Effect of a dietary intervention and n−3 fatty acid supplementation on measures of serum lipid and insulin sensitivity in persons with HIV

BACKGROUND Elevated serum triglyceride and low HDL-cholesterol concentrations have been reported in persons with HIV. OBJECTIVE The effect of a dietary intervention plus n-3 (omega-3) fatty acid supplementation on serum triglycerides and markers of insulin sensitivity was investigated. DESIGN Fifty-four persons with HIV and elevated serum triglycerides (>150 mg/dL) and/or abnormal Quantitative Insulin Sensitivity Check Index values (<0.35 but >0.30) were recruited for a dietary intervention in which total fat, type of fat, fiber, and glycemic load were controlled along with supplementation with n-3 fatty acids to achieve an intake of 6 g/d. The subjects were randomly assigned to an intervention or control group, and serum lipids, markers of insulin sensitivity, and serum phospholipid fatty acids were measured in both groups at baseline, 3 wk, and 13 wk. RESULTS Triglycerides in the intervention group decreased from a median of 180 mg/dL (interquartile range: 141, 396) to 114 mg/dL (interquartile range: 84, 169) from baseline to 3 wk, whereas they remained stable in the control group (P = 0.003). Serum phospholipid fatty acids indicated a decrease in de novo lipogenesis and a decrease in arachidonic acid (% nmol; P <or= 0.001) in the intervention group. At 3 wk, the insulin area under the curve decreased but not significantly. CONCLUSIONS Diet and n-3 fatty acid supplementation dramatically reduced serum triglycerides, decreased arachidonic acid in the phospholipids fraction, and appeared to decrease the de novo lipogenesis associated with the metabolic syndrome in the intervention group.