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The results indicate that there might have not been a progression of an HIV and STI epidemic in the past 5 years among MSM in Croatia. Prevention should expand by providing better uptake of HIV and STI testing services, thus enabling timely treatment.

Although the cardiac glycosides have been used extensively since Withering published his observations on the effects of foxglove nearly two hundred years ago (1), their distribution and metabolism and the cellular basis of their action in man are unknown. The lack of sufficiently sensitive, chemically specific methods of assay has hampered studies of the biologic behavior of these compounds.The sensitivity of available spectrophotometric and fluorometric methods is limited to 2 ,ug or more, and none of them are molecularly specific, since they involve structural components common to all cardenolides and many glycosides. Thus, production of color depends on the action of various reagents on either the lactone ring (2-11) or the 2-deoxy sugar residues (12)(13)(14)(15)(16)(17)(18)(19)(20). The a,,8-unsaturated lactone ring is also responsible for absorption of ultraviolet light at a wavelength of 217 mp (21). Fluorescence results from the action of strong acids on the steroid segment of the molecule and is attributable to dehydration and oxidation products and the formation of accessory ring structures (22)(23)(24)(25)(26)(27). All these reactions are subject to interference by numerous substances.Most current information regarding the metabolism of the cardiac glycosides is derived from studies employing bioassay methods (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) embryo heart is sensitive to 0.005 to 2 pug of cardenolide or glycoside, depending on the source of the biologic extract and the degree of purification (28)(29)(30)(31)(32)41), and even smaller quantities of glycoside labeled with 14carbon (48-50) or tritium (51-53) can be detected. Neither method, however, is intrinsically specific.Bioassay measures not only the parent compound but also its active metabolites, as well as other cardioactive substances in the sample. Similarly, radioactivity in samples from a subject given a radioisotopically labeled glycoside may represent the original compound, metabolites, or degradation products commonly formed during extraction of submicrogram quantities of steroids. Isolation of the glycoside from its metabolic products by partition with solvents (43) and by paper (39) or column (45) chromatography before bioassay or radioassay has improved specificity, but precision is impaired unless means are incorporated to correct for losses during these procedures. An additional disadvantage of the direct administration of radioisotopic compounds to human subjects is that it can be used only for acute studies.The double isotope dilution derivative method is one of the most sensitive, precise, and chemically specific methods for measuring steroids in biologic extracts (54-57). As little as 0.2 m~ug of aldosterone in peripheral plasma can be determined (56). The method has proved to be applicable to digitoxin. This paper describes the techniques employed and presents data on digitoxin in the plasma, urine, and stool of patients treated chronically with this glycoside. MethodsPrinciple of assay. A quantity of tritiu...

BackgroundAlthough considered an essential tool for monitoring the effect of combination antiretroviral treatment (CART), HIV-1 RNA (viral load, VL) testing is greatly influenced by cost and availability of resources.ObjectivesTo examine whether HIV infected patients who were initially successfully treated with CART have less frequent monitoring of VL over time and whether CART failure and other HIV-disease and sociodemographic characteristics are associated with less frequent VL testing.MethodsThe study included patients who started CART in the period 1999–2004, were older than 18 years, CART naive, had two consecutive viral load measurements of <400 copies/ml after 5 months of treatment and had continuous CART during the first 15 months. The time between two consecutive visits (days) was the outcome and associated factors were assessed using linear mixed models.ResultsWe analyzed a total of 128 patients with 1683 visits through December 2009. CART failure was observed in 31 (24%) patients. When adjusted for the follow-up time, the mean interval between two consecutive VL tests taken in patients before CART failure (155.2 days) was almost identical to the interval taken in patients who did not fail CART (155.3 days). On multivariable analysis, we found that the adjusted estimated time between visits was 150.9 days before 2003 and 177.6 in 2008/2009. A longer time between visits was observed in seafarers compared to non-seafarers; the mean difference was 30.7 days (95% CI, 14.0 to 47.4; p<0.001); and in individuals who lived more than 160 kilometers from the HIV treatment center (mean difference, 16 days, p = 0.010).ConclusionsLess frequent monitoring of VL became common in recent years and was not associated with failure. We identified seafarers as a population with special needs for CART monitoring and delivery.

Patients successfully treated for HIV infection still have an increased risk for cardiovascular morbidity and mortality, which might be related not only to traditional risks, but also to inflammation and dyslipidemia. We examined the relationship of serum lipid levels with plasma biomarkers of inflammation using a composite inflammatory burden score (IBS) based on individual (>75th percentile) measurements from the following seven markers: CD40L, tPA, MCP-1, IL-8, IL-6, hCRP and P-selectin. IBS was categorized as 0 (none of the biomarkers >75th percentile), 1, 2 and 3 or more scores. Correlations between the IBS and lipid parameters were examined by ordered logistic regression proportional odds models to estimate the odds of more elevated biomarkers. 181 male patients with undetectable HIV-viremia were included into the study. In the multivariate model, a one-unit increase (mmol/L) of total cholesterol and triglycerides was associated with a 1.41-fold (95% CI, 1.13–1.76) and 1.37-fold (95% CI, 1.18–1.60) increased odds of having a greater IBS, respectively. Those with an IBS score ≥1 compared to none had 2.14 (95% CI, 1.43–3.20) higher odds of having a one-unit increased total cholesterol/HDL-cholesterol ratio. In successfully treated HIV-infected persons dyslipidemia was associated with inflammation.

We assessed the prevalence and factors related to the time to antiretroviral (ART) initiation among persons who entered HIV care and subsequently started ART in Croatia from 2005 to 2014. Included were patients ≥ 18 years, the follow-up ended on Dec/31/2017. 628 patients were included into the study 91.9% were men; median age was 36.1 (Q1–Q3: 29.6–43.8) years. Rapid (within 7 days of diagnosis) ART initiation was observed in 21.8% patients, 49.8% initiated ART within 30 days, 21.7% and 28.5% had intermediate (31 days–1 year) and late initiation (> 1 year), respectively. Of 608 patients that achieved an undetectable viral load, 94% had a plasma HIV-1 RNA < 50 copies/ml at last measurement after a median follow-up of 5.2 years. On quantile regression analysis, calendar year of entry into care, and markers of more advanced HIV disease (higher viral load, lower CD4 cell count and clinical AIDS) were significantly associated with earlier ART initiation. Early ART was not related to a gap in care afterwards at all quantiles. In conclusion, a significant proportion of patients started ART early in Croatia in 2005–2014. Early ART initiation led to durable viral load suppression and was not associated with a subsequent gap in care.

AimTo 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.MethodsWe 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.ResultsThe 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%).ConclusionIn 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.

There are limited data on how HIV prevention interventions affect individuals presenting to care in settings with a low-level HIV epidemic. We examined whether interventions undertaken during the Croatian Global Fund Project in 2004-2006 had an influence on patients entering care. The number of men who have sex with men (MSM) presenting in 2004-2006 (n = 86) was 59% higher than in 2001-2003 (n = 54); in heterosexual patients the increase was 14% (n = 51 in 2001-2003; n = 58 in 2004-2006). MSM presented at a younger age (median 32 years) in 2004-2006 than in 2001-2003 (median 36 years). Late presentation to care was found in 28% of MSM and in 59% of heterosexual patients in 2004-2006. MSM were less frequently late presenters in 2004-2006 compared with 2001-2003 (odds ratio, 0.48; 95% confidence interval, 0.24 to 0.99; P = 0.046). Additional strategies for earlier initiation of care must be developed for MSM and particularly for heterosexual patients.