High insulin levels and increased low‐density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus

Objective

To examine low‐density lipoprotein (LDL) size, LDL susceptibility to oxidation, and plasma insulin levels in children with systemic lupus erythematosus (SLE).

Methods

Fifty‐nine SLE patients and 59 healthy, age‐matched control subjects were studied. LDL size was determined by gradient gel electrophoresis. LDL oxidizability was assessed by lag time for conjugated diene formation during copper incubation. Plasma levels of fasting insulin, glucose, lipids, lipoproteins, apolipoproteins B and A‐I, and fatty acids were also measured.

Results

Compared with control subjects, SLE patients showed significantly higher plasma insulin levels and increased susceptibility of LDLs to oxidation. Patients with active disease were more likely than patients with inactive disease or control subjects to have the following lipid characteristics: small, dense LDL subclass, elevated total cholesterol levels, elevated LDL cholesterol levels, elevated triglyceride levels, and low levels of high‐density lipoprotein cholesterol (HDL‐C). Statistically significant direct correlations were observed between disease activity and triglyceride levels and between disease activity and lag time, whereas significant inverse correlations were found between disease activity and HDL‐C levels and between disease activity and LDL size. Prednisone dosage explained only 15.6% of the variance in insulin levels.

Conclusion

SLE patients have higher plasma insulin levels and increased LDL oxidizability compared with healthy control subjects. These abnormalities may contribute to the accelerated atherosclerosis observed in patients with SLE.

     

Assessment of atherosclerotic risk factors and endothelial function in children and young adults with pediatric‐onset systemic lupus erythematosus

Objective

To characterize atherosclerotic risk factors and endothelial function in pediatric‐onset systemic lupus erythematosus (SLE).

Methods

Lipoproteins, oxidized state, and autoantibodies to oxidized low‐density lipoprotein (Ox‐LDL) were assessed. Endothelial function was evaluated using brachial artery reactivity.

Results

Thirty‐three SLE patients and 30 controls were studied. SLE subjects had significantly decreased mean high‐density lipoprotein (HDL) cholesterol (41 mg/dl versus 51 mg/dl; P = 0.002) and apolipoprotein A‐I (97 mg/dl versus 199 mg/dl; P = 0.0004). There was no difference between groups in markers of oxidized state (including nitric oxide metabolites, isoprostanes, and Ox‐LDL) or in endothelial function. However, SLE subjects had increased median anti‐Ox‐LDL IgG (2,480 relative light units [RLU] versus 1,567 RLU; P = 0.0007) and IgG immune complexes with LDL (4,222 RLU versus 2,868 RLU; P = 0.002).

Conclusion

Pediatric SLE patients had significantly decreased levels of HDL cholesterol and apolipoprotein A‐I and elevated titers of autoantibodies to Ox‐LDL. Despite these atherosclerotic risk factors, SLE patients had normal measures of oxidized state and endothelial function.

     

HIV/HBV and HIV/HCV coinfection,and outcomes following highly active antiretroviral therapy

Objectives

To assess the prevalence and risk factors for HBV and HCV coinfection in the Australia HIV Observational Database (AHOD), and examine outcomes of HIV disease following initiation of highly active antiretroviral therapy (HAART).

Methods

Analyses were based on 2086 participants recruited to AHOD by September 2002. Of these, 1605 (77%) had been tested for HBV surface antigen, 1704 (82%) for anti‐HCV antibody and 1453 (70%) for both. Demographic and clinical predictors of HBV and HCV coinfection were examined. The impact of HBV and HCV coinfection on HIV disease progression was assessed by Kaplan‐Meier survival curves and Cox proportional hazard model of time to AIDS events and death.

Results

Among those tested, prevalence of HBV surface antigen and HCV antibody were 6.3% and 13.1%, respectively (4.8% and 10.7%, respectively, among the entire cohort). In multivariate analyses, the only independent risk factor for HIV/HBV coinfection was coinfection with HCV. Independent risk factors for HIV/HCV coinfection were HIV exposure category (with people who reported injecting drug use [MSM & IDU, IDU only] or receipt of blood or blood products at markedly increased risk) and HBV coinfection. HIV disease outcomes following first initiation of a HAART regimen were similar for HIV/HBV and HIV/HCV coinfected patients compared with HIV‐only patients in terms of AIDS‐free survival and detectable HIV virus during the first 12 months. However, patients coinfected with HIV/HCV appeared to have a poorer response to HAART in terms of CD4 count changes, with a CD4 count increase of 32 cells/μL (95% CI 1–67) less than HIV‐only patients.

Conclusions

Coinfection with HBV or HCV is relatively common among HIV‐infected participants in AHOD. HIV disease outcomes following HAART do not appear to be adversely affected by HBV/HCV coinfection, except for slightly poorer CD4 count responses in HIV/HCV coinfected patients.

     

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis

Objective

The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)‐coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6‐month period, in a group of 381 HIV/HCV‐coinfected patients.

Methods

Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined.

Results

Thirty‐six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28–0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20–0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15–6.68; P=0.023) were associated with persistently normal ALT levels.

Conclusion

The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis

     

Effects of ritonavir-boosted darunavir vs. ritonavir-boosted atazanavir on lipid and glucose parameters in HIV-negative, healthy volunteers

Background

Darunavir (TMC114) is a new HIV protease inhibitor (PI).

Design

This Phase I, randomized, open‐label trial compared the effects of darunavir plus low‐dose ritonavir (RTV) (darunavir/RTV) with those of atazanavir/RTV on lipid and glucose parameters.

Methods

Forty‐nine HIV‐negative, healthy male volunteers received RTV 100 mg once a day (qd) for 7 days, followed by either darunavir/RTV 800/100 mg qd (n=25) or atazanavir/RTV 300/100 mg qd (n=24) for 21 days. Mean changes in fasting lipid and glucose parameters at day 28 were calculated using post‐RTV alone (day 7) and baseline (day ?1) values as references. Short‐term safety, tolerability and RTV pharmacokinetic parameters were evaluated.

Results

After 7 days of RTV treatment, the mean triglyceride concentration increased by approximately 30 mg/dL in both groups, changes in other lipid and glucose parameters were relatively small. Mean concentrations of lipids and glucose over the treatment period were mostly similar between the treatment groups. Mean changes from day 7 to day 28 for the darunavir/RTV and atazanavir/RTV groups, respectively, were ?3.6 and ?0.5 mg/dL for high‐density lipoprotein cholesterol; 5.0 and 5.3 mg/dL for low‐density lipoprotein cholesterol; 4.9 and 1.2 mg/dL for total cholesterol; 6.4 and 14.0 mg/dL for triglycerides; ?1.7 and ?2.4 mg/dL for glucose; and ?1.4 and 0.3 mg/dL for insulin. No grade 3 or 4 lipid or glucose laboratory abnormalities were reported. Treatment‐emergent hyperbilirubinaemia was reported for all volunteers (including five grade 4 cases) during atazanavir/RTV treatment.

Conclusions

Co‐administration of darunavir or atazanavir with low‐dose RTV resulted in minor and similar changes in lipid and glucose parameters in HIV‐negative healthy volunteers.

     

Pitfalls in measuring high‐density lipoprotein cholesterol concentrations in HIV‐infected patients

Objectives

HIV infection and its treatment are associated with dyslipidaemia and increased risk of cardiovascular disease. Accurate high‐density lipoprotein (HDL) cholesterol values are necessary for the management of these abnormalities, but current methods have not been properly assessed in these patients. The aim of this study was to assess in HIV‐infected patients the consistency and accuracy of a synthetic polymer/detergent homogeneous assay used to measure HDL cholesterol concentrations and to evaluate the impact of storage.

Methods

HDL cholesterol was measured using a synthetic polymer/detergent homogeneous method in samples from HIV‐infected patients and healthy subjects for each of the storage regimens: baseline, after 1 week at 4 °C, and after 12 months at −80 °C. The ultracentrifugation and precipitation assays were used for comparison.

Results

Three out of every 20 samples from HIV‐infected patients had discrepant HDL cholesterol values with respect to the ultracentrifugation method. Overestimation was associated with high C‐reactive protein concentrations and underestimation with plasma γ‐globulin concentrations, an effect that was amplified by any of the storage conditions tested.

Conclusions

Caution is needed when using the synthetic polymer/detergent homogeneous method for direct measurement of HDL cholesterol concentrations in HIV‐infected patients. This assay is of limited use in clinical trials in which frozen samples are analysed.

     

Persistence of CCR5 usage among primary human immunodeficiency virus isolates of individuals receiving intermittent interleukin‐2

Objective

To investigate the impact of intermittent interleukin‐2 (IL‐2) plus combination antiretroviral therapy (cART) on HIV‐1 entry co‐receptor use.

Methods

Primary HIV‐1 isolates were obtained from 54 HIV‐1‐positive individuals at baseline and after 12 months using co‐cultivation of peripheral blood mononuclear cells (PBMC) with activated PBMC of HIV‐negative healthy donors. HIV‐1 co‐receptor use was determined on U87‐CD4 cells.

Results

Fourteen out of the 21 (67%) IL‐2‐treated individuals harbouring a primary CCR5‐dependent (R5) HIV‐1 isolate at baseline confirmed an R5 virus isolation after 12 months in contrast to 3 out of 7 (43%) of those receiving cART only. After 12 months, only 1 R5X4 HIV‐1 isolate was obtained from 21 cART+IL‐2‐treated individuals infected with an R5 virus at entry (5%) vs. 2/7 (29%) patients receiving cART alone, as confirmed by a 5‐year follow‐up on some individuals.

Conclusions

Intermittent IL‐2 administration plus cART may prevent evolution towards CXCR4 usage in individuals infected with R5 HIV‐1.

     

Gemfibrozil decreases autoantibodies against oxidized low-density lipoprotein in men with combined hyperlipidaemia

Hoogerbrugge N, Kerkhofs LGN, Jansen H (University Hospital Dijkzigt, Rotterdam, The Netherlands). Gemfibrozil decreases autoantibodies against oxidized low-density lipoprotein in men with combined hyperlipidaemia. J Intern Med 1998; 243 : 355–59.

Objectives

Gemfibrozil is the most widely used fibric acid for the management of combined hyperlipidaemia. It has beneficial effects in the prevention of coronary heart disease (CHD). The mechanisms by which it exerts this effect are not completely resolved. We studied whether gemfibrozil affects low-density lipoprotein (LDL) size and LDL oxidation parameters in males with a moderate combined hyperlipidaemia at high risk for progressive atherosclerosis.

Design

Open treatment with 2 × 600 mg gemfibrozil daily for 12 weeks.

Setting

Outpatient lipid clinic of a tertiary referral centre.

Subjects

Twenty-three patients with combined hyperlipidaemia and CHD or a positive family history for both CHD and hyperlipidaemia.

Main outcome measures

Effects on triglyceride (TG), autoantibodies to oxidized LDL, LDL pattern and resistance to oxidative modification.

Results

During treatment with gemfibrozil, plasma TG concentration decreased from 2.83 ± 0.85 to 2.02 ± 0.89 mmol L^?1 (P < 0.001). All but one patient were shown to have LDL pattern B. The LDL pattern did not change upon treatment with gemfibrozil. The resistance to oxidation, reflected in the lagtime during in-vitro oxidation slightly decreased from 105 ± 22 to 99 ± 18 min (P= 0.01). The concentration of autoantibodies against oxidized LDL indicates the rate of LDL oxidation in vivo. This concentration significantly decreased from 14.2 ± 9.9 to 13.1 ± 9.2 mg L^?1 (P < 0.01).

Conclusions

The beneficial effect of gemfibrozil in reducing CHD may at least in part depend on a decrease of the rate of LDL oxidation in vivo.

     

PENTA guidelines for the use of antiretroviral therapy in paediatric HIV infection. Pediatric European Network for Treatment of AIDS

Objective

To produce European Guidelines for the use of antiretroviral therapy (ART) in HIV‐infected children.

Design

Systematic literature review using Medline, the major antiretroviral conference reports, and IDSA recommendations on guideline production.

Setting

Pediatric European Network for Treatment of AIDS (PENTA) Steering Committee.

Outcome measure

Guidelines have been produced for the use of antiretroviral therapy in HIV‐infected children in Europe. Recommendations on when to start ART and which ART to start, with dosages and a summary of the relevant literature, have been produced.

Conclusions

These guidelines are aimed at assisting paediatricians in Europe with ART prescribing, and provide a more cautious approach to starting therapy than current paediatric USA guidelines.

     

Individuals with high total cholesterol/hdl cholesterol ratios are insulin resistant

Jeppesen J, Facchini FS, Reaven GM. (The Department of Medicine, Stanford University School of Medicine, Stanford, and Shaman Pharmaceuticals Inc., South San Francisco, CA, USA). Individuals with high total cholesterol/hdl cholesterol ratios are insulin resistant. Journal of Internal Medicine 1998; 243 : 293–98.

Objectives

To define the pathophysiologic characteristics of patients at high risk for coronary heart disease due to an increased ratio of total cholesterol (TC) to high density lipoprotein-cholesterol (HDL-C).

Design

Cross-sectional.

Setting

Clinical Research Center.

Subjects

One hundred-20 healthy, non-diabetic, normotensive, volunteers were screened for this study. From this pool, 40 individuals (20 females and 20 males) with the highest and the lowest TC/HDL-C ratios were selected for comparison.

Main Outcome Measures

Values for body mass index (BMI), ratio of waist to hip girth (WHR), and blood pressure were obtained on all patients. In addition, measurements were made of fasting lipid and lipoprotein concentrations, plasma glucose and insulin responses to an oral glucose challenge, and insulin resistance as assessed by the insulin suppression test.

Results

Age, BMI, and WHR were the same in the two groups. However, the group with a high TC/HDL-C ratio had higher (P < 0.05) systolic and diastolic blood pressures. In addition, patients with a high TC/HDL-C ratio had significantly higher (P < 0.001) very low density (VLDL) and low density lipoprotein (LDL)-cholesterol concentrations and lower HDL-cholesterol concentrations, with significant (P < 0.001) correlations between the TC/HDL-C ratio and VLDL (r= 0.60), LDL (r= 0.54), and HDL (r=? 0.73) cholesterol concentrations. Patients with a high TC/HDL-C ratio were also significantly (P < 0.05–0.001) more insulin resistant, glucose intolerant with a greater plasma insulin response to oral glucose, and hypertriglyceridemic.

Conclusions

The results indicate that an increase in LDL-cholesterol concentration is not necessarily the major contributor to a high ratio of TC/HDL-C. Furthermore, individuals with this epidemiologic designation are insulin resistant, and liable to all the other abnormalities associated with this metaboic defect.

     

Low plasma levels of dehydroepiandrosterone sulphate in HIV-positive patients coinfected with hepatitis C virus

Objectives

To evaluate plasma levels of dehydroepiandrosterone sulphate (DHEAS) in a cohort of HIV‐infected patients and to analyse factors associated with DHEAS levels.

Methods

We conducted a cross‐sectional survey in the Nîmes University Hospital cohort of HIV‐infected patients in south‐eastern France. All HIV‐infected patients with at least one outpatient visit between 1 January and 1 September 2002 were included in the study. Sociodemographic, clinical, therapeutic, immuno‐virological and plasma DHEAS level data were collected during this period. Hepatitis C virus (HCV) coinfection was defined as the presence of HCV antibody with positive RNA. To identify factors associated with plasma DHEAS levels, Spearman's rank correlation and univariate and multivariate linear regression analyses were used.

Results

The DHEAS plasma level was measured in 137 patients (104 men and 33 women), 37 (27.0%) of whom were HCV coinfected. The median age of the patients was 39.1 years [interquartile range (IQR): 34.9–48.7] for women and 41.8 years (36.5–47.7) for men. The median DHEAS level was 5.5 μmol/L (IQR: 2.3–8.8) for the whole sample of 137 patients, and was lower in women (2.4 μmol/L; 1.5–6.6) than in men (6.1 μmol/L; 2.5–9.0) (P<0.01), and lower in patients coinfected with HCV (2.1 μmol/L; 0.6–6.7) than in those not coinfected (6.6 μmol/L; 3.0–9.1) (P<0.01). Of all prognostic factors studied in the variance covariance analysis, three factors were associated with DHEAS: age, gender and HCV coinfection. Subgroup analysis revealed that the age‐adjusted mean of the DHEAS level was lower in HCV coinfected patients for both women (1.3±1.1 μmol/L) and men (4.0±0.7 μmol/L), compared with patients not HCV coinfected (women, 5.3±0.7 μmol/L; men, 7.2±0.4 μmol/L) (P<0.01).

Conclusions

This is the first report of the determination of DHEAS plasma levels in HIV/HCV coinfected patients. When age and sex were taken into account, the DHEAS plasma level was found to be significantly lower in HCV coinfected patients. To date, the pathophysiology of such findings is unknown.

     

Effect of simplification from protease inhibitors to boosted atazanavir‐based regimens in real‐life conditions

Background

Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well‐tolerated, once‐daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs.

Objective

The aim of the study was to determine the effectiveness and safety of ATV‐containing regimens in patients who have simplified their antiretroviral treatment.

Methods

SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI‐containing therapy and who were switched to an ATV/r‐based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction.

Results

A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/μL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low‐density lipoprotein cholesterol were ?13 mg/dL (?7%; P<0.0001), ?19 mg/dL (?13%; P<0.0001) and ?7 mg/dL (?6%; P=0.021), respectively.

Conclusions

In a real‐world setting, switching from other PIs to ATV/r is a well‐tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

     

The effects of statin monotherapy and low-dose statin/ezetimibe on lipoprotein-associated phospholipase A₂

Background

Many of the pleiotropic effects of statins remain to be elucidated.

Hypothesis

Different statin regimens with similar lipid‐lowering efficacy may have different effects on biomarkers of atherothrombosis including lipoprotein‐associated phospholipase A₂ (Lp‐PLA₂).

Methods

After a 4‐week dietary lead‐in, 82 hypercholesterolemic patients were randomized to 1 of 2 treatment groups: atorvastatin 20 mg or atorvastatin/ezetimibe 5 mg/5 mg. After 8 weeks of drug treatment, the groups were compared for percent change in lipid parameters, Lp‐PLA₂, interleukin‐6 (IL‐6), monocyte chemoattractant protein‐1, and fibrinogen.

Results

Low‐density lipoprotein cholesterol (LDL‐C) lowering was comparable between the 2 groups (?47% ± 11% and ?49% ± 7% in the atorvastatin and combination groups, respectively). Although Lp‐PLA₂ was reduced in both groups, the reduction was greater in the atorvastatin group (?42% and ?9% [median], respectively, P = 0.03). Although IL‐6 was decreased only in the atorvastatin group, IL‐6 changes were not significantly different between the 2 groups. The changes in monocyte chemoattractant protein‐1 and fibrinogen were similar in each group.

Conclusions

Atorvastatin monotherapy was stronger at reducing plasma Lp‐PLA₂ than the low‐dose atorvastatin/ezetimibe combination after equivalent LDL‐C lowering. This result may provide evidence of potential statin effects beyond the lowering of LDL‐C. Copyright © 2011 Wiley Periodicals, Inc. This study was supported by a grant from the Ministry of Health and Welfare, Republic of Korea (A000385), a grant of the Seoul R&BD Program, Republic of Korea (10526), and a grant of the Korean Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A085136). The authors have no other funding, financial relationships, or conflicts of interest to disclose.

     

Nonconcordance between subclinical atherosclerosis and the calculated Framingham risk score in HIV‐infected patients: relationships with serum markers of oxidation and inflammation

Objectives

HIV‐infected patients show an increased cardiovascular disease (CVD) risk resulting, essentially, from metabolic disturbances related to chronic infection and antiretroviral treatments. The aims of this study were: (1) to evaluate the agreement between the CVD risk estimated using the Framingham risk score (FRS) and the observed presence of subclinical atherosclerosis in HIV‐infected patients; (2) to investigate the relationships between CVD and plasma biomarkers of oxidation and inflammation.

Methods

Atherosclerosis was evaluated in 187 HIV‐infected patients by measuring the carotid intima‐media thickness (CIMT). CVD risk was estimated using the FRS. We also measured the circulating levels of interleukin‐6, monocyte chemoattractant protein‐1 (MCP‐1) and oxidized low‐density lipoprotein (LDL), and paraoxonase‐1 activity and concentration.

Results

There was a weak, albeit statistically significant, agreement between FRS and CIMT (κ=0.229, P<0.001). A high proportion of patients with an estimated low risk had subclinical atherosclerosis (n=66; 56.4%). In a multivariate analysis, the presence of subclinical atherosclerosis in this subgroup of patients was associated with age [odds ratio (OR) 1.285; 95% confidence interval (CI) 1.084–1.524; P=0.004], body mass index (OR 0.799; 95% CI 0.642–0.994; P=0.044), MCP‐1 (OR 1.027; 95% CI 1.004–1.050; P=0.020) and oxidized LDL (OR 1.026; 95% CI 1.001–1.051; P=0.041).

Conclusion

FRS underestimated the presence of subclinical atherosclerosis in HIV‐infected patients. The increased CVD risk was related, in part, to the chronic oxidative stress and inflammatory status associated with this patient population.

     

Reduction of atherosclerosis in low‐density lipoprotein receptor–deficient mice by passive administration of antiphospholipid antibody

Objective

Patients with antiphospholipid syndrome (APS) are at a high risk of developing atherosclerotic complications. Conversely, individuals with primary atherosclerosis have an increased prevalence of antiphospholipid antibodies (aPL) and antibodies to oxidized low‐density lipoproteins (ox‐LDL). Several studies suggest that these two antibody populations may in fact overlap, although it is unclear how aPL contribute to pathogenesis. In this study, we characterized an IgG monoclonal aPL and assessed its ability to modulate atherosclerosis in low‐density lipoprotein receptor–deficient (LDLR^−/−) mice.

Methods

The cardiolipin‐reactive monoclonal antibody FB1 was obtained from an (NZW × BXSB)F₁ mouse, a strain with APS features that make it prone to fatal myocardial infarctions. Using an enzyme‐linked immunosorbent assay, we investigated the binding of this antibody to phospholipid and LDL antigens. We also passively administered FB1 to atherosclerosis‐prone mice to determine its effect on atherogenesis.

Results

In contrast to earlier studies of aPL that were specific for oxidized forms of LDL, FB1 cross‐reacted with both native LDL and ox‐LDL. In vivo, passive administration of FB1 significantly reduced plaque formation in atherosclerosis‐prone LDLR^−/− mice.

Conclusion

These results indicate that some aPL may play a protective role in atherogenesis and suggest a novel approach to the prevention of atherosclerosis.

     

Anti–tumor necrosis factor agents for rheumatoid arthritis in the setting of chronic hepatitis C infection

Objective

To examine the safety of using anti–tumor necrosis factor (TNF) therapy in patients with rheumatoid arthritis (RA) in the setting of hepatitis C virus (HCV) infection.

Methods

The charts of 5 patients known to have RA requiring anti‐TNF therapy as well as established HCV infection were reviewed retrospectively for laboratory data of hepatic parenchymal inflammation and viral proliferation while taking these agents.

Results

In a mean ± SD followup period of 41 months (± 28.2 months), no patient displayed evidence of sustained elevation of serum aminotransferases during therapy with anti‐TNF. Additionally, 1 patient was observed to have a decreased HCV viral load after extended treatment with only anti‐TNF (no therapy for HCV).

Conclusion

Anti‐TNF therapy for RA in the setting of HCV appears to be safe and well tolerated without apparent influence on the underlying HCV infection. Therefore, this approach should be further evaluated prospectively for longterm safety.

     

Serum lipid profile in highly active antiretroviral therapy‐naïve HIV‐infected patients in Cameroon: a case–control study

Background

HIV status has commonly been found to affect the serum lipid profile.

Objectives

The aim of this study was to determine the effect of HIV infection on lipid metabolism; such information may be used to improve the management of HIV‐infected patients.

Methods

Samples were collected from December 2005 to May 2006 at Yaounde University Teaching Hospital, Yaounde, Cameroon. Lipid parameters were obtained using colorimetric enzyme assays, while low‐density lipoprotein cholesterol (LDLC) values were calculated using the formula of Friedewald et al. (1972) and atherogenicity index by total cholesterol (TC)/high‐density lipoprotein cholesterol (HDLC) and LDLC/HDLC ratios.

Results

HIV infection was most prevalent in subjects aged 31 to 49 years. Most of the HIV‐positive patients belonged to Centers for Disease Control and Prevention categories B (43.0%) and C (30.23%). Compared with control subjects, patients with CD4 counts<50 cells/μL had significantly lower TC (P<0.0001) and LDLC (P<0.0001) but significantly higher triglyceride (TG) values (P<0.001) and a higher atherogenicity index for TC/HDLC (P<0.01) and HDLC/LDLC (P=0.02); patients with CD4 counts of 50–199 cells/μL had significantly lower TC (P<0.001) and significantly higher TG values (P<0.001); patients with CD4 counts of 200–350 cells/μL had significantly higher TG (P=0.003) and a higher atherogenicity index for TC/HDLC (P<0.0002) and HDLC/LDLC (P=0.04); and those with CD4 counts >350 cells/μL had a higher atherogenicity index for TC/HDLC (P<0.0001) and HDLC/LDLC (P<0.001). HDLC was significantly lower in HIV‐positive patients irrespective of the CD4 cell count. Lipid parameters were also influenced by the presence of opportunistic infections (OIs).

Conclusion

HIV infection is associated with dyslipidaemia, and becomes increasingly debilitating as immunodeficiency progresses. HDLC was found to be lower than in controls in the early stages of HIV infection, while TG and the atherogenicity index increased and TC and LDLC decreased in the advanced stages of immunodeficiency.

     

Lipid profiles for nevirapine vs. atazanavir/ritonavir, both combined with tenofovir disoproxil fumarate and emtricitabine over 48 weeks, in treatment-naïve HIV-1-infected patients (the ARTEN study)

Objectives

Dyslipidaemic effects of antiretrovirals (ARVs) may contribute to increased cardiovascular risk (CR) in HIV‐1‐infected patients. The ARTEN (atazanavir/ritonavir on a background of tenofovir and emtricitabine vs. nevirapine on the same background, in naïve HIV‐1‐infected patients) study compared prospectively ritonavir‐boosted atazanavir (ATZ/r) 300 mg/100 mg once daily (qd) with immediate release nevirapine (NVP) 200 mg twice daily or 400 mg qd, each combined with fixed‐dose tenofovir 300 mg/emtricitabine 200 mg qd in 569 ARV‐naïve HIV‐1‐infected patients. Lipid profiles and CR from baseline to week 48 are reported.

Methods

Changes from baseline to week 48 in fasting plasma levels of total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐c), low‐density lipoprotein cholesterol (LDL‐c), TC:HDL‐c ratio, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total triglycerides (TG) were determined. The Framingham algorithm was used to estimate CR. Analysis was by intention‐to‐treat (ITT) with last observation carried forward (LOCF) for missing data.

Results

At week 48, NVP treatment resulted in significantly greater mean increases from baseline in TC (24.4 vs. 19.6 mg/dL; P=0.038), HDL‐c (9.7 vs. 3.9 mg/dL; P<0.0001), LDL‐c (15.0 vs. 10.4 mg/dL; P=0.011) and ApoA1 (0.18 vs. 0.08 g/L; P<0.0001) but not ApoB (0.02 vs. 0.02 g/L) compared with ATZ/r treatment. ATZ/r use was associated with higher mean TG increases (27.80 vs. 0.02 mg/dL; P=0.0001). Significantly greater mean decreases in TC:HDL‐c and ApoB/ApoA ratios were observed with NVP vs. ATZ/r (P=0.0001 and P=0.008, respectively). Framingham CR scores were low and comparable between the arms, with only a slight mean increase from baseline to week 48 of 0.70 for NVP and 0.80 for ATZ/r [difference ?0.069; 95% confidence interval (CI) ?0.61 to 0.46; P=0.80].

Conclusions

In ARV‐naïve patients with low CR at the outset, NVP showed a potentially less atherogenic lipid profile compared with ATZ/r.