Jovana Kušić

Comparison of four international cardiovascular disease prediction models and the prevalence of eligibility for lipid lowering therapy in HIV infected patients on antiretroviral therapy.

Aim To compare four cardiovascular disease (CVD) risk models and to assess the prevalence of eligibility for lipid lowering therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, European AIDS Clinical Society Guidelines (EACS), and European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS) guidelines for CVD prevention in HIV infected patients on antiretroviral therapy. Methods We performed a cross-sectional analysis of 254 consecutive HIV infected patients aged 40 to 79 years who received antiretroviral therapy for at least 12 months. The patients were examined at the HIV-treatment centers in Belgrade and Zagreb in the period February-April 2011. We compared the following four CVD risk models: the Framingham risk score (FRS), European Systematic Coronary Risk Evaluation Score (SCORE), the Data Collection on Adverse Effects of Anti-HIV Drugs study (DAD), and the Pooled Cohort Atherosclerotic CVD risk (ASCVD) equations. Results The prevalence of current smoking was 42.9%, hypertension 31.5%, and hypercholesterolemia (>6.2 mmol/L) 35.4%; 33.1% persons were overweight, 11.8% were obese, and 30.3% had metabolic syndrome. A high 5-year DAD CVD risk score (>5%) had substantial agreement with the elevated (≥7.5%) 10-year ASCVD risk equation score (kappa = 0.63). 21.3% persons were eligible for statin therapy according to EACS (95% confidence intervals [CI], 16.3% to 27.4%), 25.6% according to ESC/EAS (95% CI, 20.2% to 31.9%), and 37.9% according to ACC/AHA guidelines (95% CI, 31.6 to 44.6%). Conclusion In our sample, agreement between the high DAD CVD risk score and other CVD high risk scores was not very good. The ACC/AHA guidelines would recommend statins more often than ESC/EAS and EACS guidelines. Current recommendations on treatment of dyslipidemia should be applied with caution in the HIV infected population.

CYP2B6 516G>T (rs3745274) and smoking status are associated with efavirenz plasma concentration in a Serbian cohort of HIV patients.

Background: Genetic factors have been associated with efavirenz (EFV) plasma concentrations in different populations. In this study, we investigated the effects of CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), CAR c.152-1089T>C (rs3003596), and smoking status in a cohort of Serbian patients with HIV. Methods: Patients with HIV positive, all whites, were recruited from the HIV/AIDS Center at the Infectious and Tropical Diseases Hospital, University of Belgrade Teaching Hospital, Belgrade, Serbia. Mid dose (10–14 hours after dose) EFV plasma concentration was determined using a validated liquid chromatography/tandem mass spectrometry method. Genotyping for CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), and CAR c.152-1089T>C (rs3003596) was conducted using allelic discrimination real-time polymerase chain reaction assay. One-way analysis of variance, Mann–Whitney test, Pearson or Spearman correlation, and multiple linear regression were used for data analysis. Results: Minor allele frequencies were similar to frequencies reported in other European populations. The overall mean (95% confidence interval) plasma EFV concentration was 2800 ng/mL (2460–3140). Significant differences between patients based on CYP2B6 516G>T (rs3745274) genotypes were observed: GG (n = 60), 2320 (range, 2160–2480) ng/mL; GT (n = 30), 3230 (range, 2790–3670) ng/mL; and TT (n = 2), 10,700 (range, 6170–15,300) ng/mL (P = 2.0 × 10−17). In multivariate linear regression analysis, CYP2B6 516G>T (rs3745274) [&bgr; = 1770 (1230 to 2310) ng/mL, P < 0.0001] and smoking status [&bgr; = −464 (−1250 to −43.3) ng/mL, P = 0.038] were independently associated with plasma EFV concentrations. Conclusions: The effects of CYP2B6 516G>T (rs3745274) and smoking status on EFV plasma concentration in the Serbian population have been established for the first time.

Clinical and Immunologic Outcomes of HAART-Treated HIV-Infected Women in Resource Constrain Settings: The Belgrade Study

We performed a study to identify factors related to favorable response to highly active-antiretroviral therapy (HAART) in HIV-infected women. A retrospective study was performed on 216 women who had initiated HAART from January 1, 1998 to December 31, 2012, at the HIV/AIDS Center, Belgrade, Serbia. Participants were followed-up for 8.2 ± 3.4 years. The mean age was 37 ± 9.7 years. During follow-up, it was found that 26 patients had died. Clinical AIDS at initiation of HAART was observed in 43.9% patients, while 64.8% had a CD4+ T-cell count below 200 cells/μL. Multivariate analyses revealed that the single factor independently related to a favorable response to HAART was good compliance (odds [OR] ratio for survival = 2.9, 95% confidence intervals [CI] = 1.0–8.6, p = 0.03), while a baseline CD4+ T-cell count below 100 cells/μL, hepatitis C virus coinfection, and aged 40 years and older were all associated with an unfavorable response to HAART (OR = 0.28, 95% CI = 0.15–0.52, p < 0.001; OR = 0.49, 95% CI = 0.22–0.8, p = 0.008; OR = 0.41, 95% CI = 0.21–0.79, p = 0.008, respectively). The estimated 14-year-survival was 100% in patients with sustained viral suppression, regardless of the CD4+ counts achieved (p = 0.6, log-rank). If women with advanced HIV-related immunodeficiency reach and maintain optimal viral suppression during HAART, regardless of the level of immune recovery, and if they continue to maintain this suppression for up to a mean 8 years of treatment, their prognosis may be fairly good, even in resource-limited settings.

Prevalence and concordance of high cardiovascular disease scores in HIV/AIDS patients from Croatia and Serbia with four international algorithms

We evaluated cardiovascular risks in HIV‐infected patients from Croatia and Serbia and the eligibility for statin therapy as recommended by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, European AIDS Clinical Society (EACS) Guidelines and European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS) guidelines for cardiovascular disease (CVD) prevention [ 1 – 3 ].

HIV/AIDS mortality in a south east European country versus a west European country

Antiretroviral (ARV) treatment available in low‐middle income countries differs as suggested in international HIV‐treatment guidelines. Thus, we compared ARV regimens introduced as a first‐line therapy, time of initiation, frequency of making combination antiretroviral therapy (cART) switches, frequency of viral and immunological monitoring and treatment outcome in south east European (SEE) country (i.e. HIV Centre in Belgrade, Serbia, (HCB)) and west European country (i.e. Royal Free Centre for HIV Medicine at the Royal Free Hospital London, UK (RFH)).

Higher Levels of CYSTATIN C in HIV/AIDS Patients with Metabolic Syndrome

Data about Cystatin‐C levels in HIV‐infected patients with metabolic syndrome (MetS) are still limited. Therefore, the aim of this study was to evaluate the possible correlations of serum levels of Cystatin‐C in HIV/AIDS patients treated with combined antiretroviral therapy (cART) with or without MetS. This cross‐sectional study included 89 HIV/AIDS Caucasian patients receiving cART at the HIV/AIDS Centre Belgrade, Serbia, divided into two groups according to the presence of MetS. Cystatin‐C and other biochemical parameters were measured using Cytokine‐Array‐I, Metabolic‐Array‐I and Metabolic‐Array‐II, at the Department of Clinical Biochemistry, Royal Free Hospital and University College London, UK. A linear regression model was performed to evaluate which clinical and laboratory variables had an independent effect on Cystatin‐C levels in HIV/AIDS patients. There were 33 (37%) patients with MetS and 56 (63%) without MetS. Patients with and without MetS were homogenous for age, duration of cART, number of cART combinations and CD4+ T cell count. Statistically increased Cystatin‐C levels were observed in HIV/AIDS patients with MetS (p = 0.017), when compared to patients without MetS. Data showed a positive correlation of Cystatin‐C and C‐reactive protein (r = 0.349, p = 0.001). Using linear regression modelling, significant correlations were obtained between Cystatin‐C and MetS in univariate analysis (p < 0.001). Cystatin‐C levels were significantly higher in HIV/AIDS patients with MetS versus without MetS. Early assessment of MetS using Cystatin‐C as a marker may ultimately help increase the lifespan of HIV/AIDS patients, as these patients appear to be at high risk of cardiovascular diseases.