Cost-effective osteoporosis treatment thresholds for people living with HIV infection in Greece.

OBJECTIVES: We aimed to specifically define the FRAX-based cost-effective treatment thresholds for osteoporosis among people living with HIV (PLWHIV) in Greece and to compare them with those of the general population. METHODS: A previously described state transition Markov cohort model was used in order to estimate the cost-effective intervention thresholds for osteoporotic therapy among Greek PLWHIV employing the FRAX® tool. The model-derived relative risk at which an incremental cost-effectiveness ratio of 30,000€/QALY gained was observed for treatment versus no intervention was multiplied by the average Greek FRAX-based 10-year probabilities for both major osteoporotic and hip fractures. RESULTS: There exists no significant difference in the cost-effective FRAX® based thresholds between PLWHIV and general population. The absolute 10-year probabilities of 2.5 and 10% for hip and major osteoporotic fractures, respectively, could be used for the initiation of treatment for PLWHIV of both genders under the age of 75; for older subjects the proposed intervention threshold is raised to 5 and 15% 10-year probability for hip and major osteoporotic fracture, respectively. CONCLUSIONS: Our study confirms the general recommendation for the use of country specific FRAX® thresholds when managing bone fragility within PLWHIV. In any case, clinical judgment and appropriate screening are mandatory and irreplaceable.

A switch to Raltegravir improves antiretroviral associated hepatotoxicity in individuals co-infected with HIV and hepatitis C.

INTRODUCTION: Raltegravir is a switch option for HIV/HCV co-infected individuals due to its hepatic neutral profile. We evaluated the effect of a switch to Raltegravir from other antiretroviral agents in HIV and HCV-co-infected individuals naïve to HCV therapy. METHODS: Observational, single-centre study. Data on alanine aminotransferase levels, HCV-VL, CD4 cell count, HIV viral load levels and hepatic fibrosis score were collated six months pre-switch, at the time of switch and six months post switch to Raltegravir therapy. Results were compared utilizing the Kruskal-Wallis test. RESULTS: Twenty-seven individuals were identified. Median age was 43 years, median duration of HIV infection was 7 years and median documented period of HCV infection at the time of switch was 26 months. A sustained improvement in ALT levels was observed. Median ALT levels were 254 IU/L at the time of switch, decreasing significantly to 176 IU/L, (p = 0.0226) and 90 IU/L (p = 0.0138) 1 month post switch and 6 months post switch respectively. The median Hepatitis C viral load level at the time of the switch was 341,783 copies/mL, which decreased to 224,066 copies/mL 6 months after switch (p = 0.04). DISCUSSION: A switch to Raltegravir in individuals with HIV/HCV co-infection was effective in maintaining HIV virological suppression with improvement in drug-associated hepatotoxicity as measured by ALT.

High prevalence of the UGT1A1*28 variant in HIV-infected individuals in Greece.

Hyperbilirubinaemia with or without jaundice is one of the side effects of atazanavir boosted with low-dose ritonavir (ATV/rit) related to the drug plasma levels, as a result of its metabolism by UGT1A1 - uridine diphosphate-glucuronosyl transferase. Genotyping for UGT1A1*28 before initiation of antiretroviral therapy containing atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Our objective was to estimate the prevalence of the UGTA1A1*28 polymorphism in HIV-infected individuals in Greece and to determine its potential association with hyperbilirubinaemia in patients receiving ATV/rit. The prevalence of the UGTA1A1*28 variant was estimated in 79 HIV-infected patients prior to the administration of the first-line treatment. The UGTA1A1*28 variant was detected in 46 out of 79 individuals (58.2%). Antiretroviral therapy was administered to 64/79 patients (81%). Among them, 26/64 (40.6%) received ATV/rit. Of the ATV/rit-treated patients, 14 were found to be carriers of the UGT1A1*28 variant (54%), and maximum serum bilirubin levels were significantly higher in the carrier population (4.71 vs. 2.69 mg/dL, p = 0.026). In 50% of the population, maximum levels were recorded in the first month of follow-up. Although carriage of UGT1A1 is linked with the development of hyperbilirubinaemia, the implementation of a pharmacogenomic approach in clinical practice cannot yet be recommended as a standard of care.

Fluoroquinolone treatment of chronic bacterial prostatitis: a prospective cohort study.

A cohort study of patients (pts) presenting with symptoms of chronic prostatitis over 2 years was performed. Appropriate antimicrobials were administered to confirmed cases of chronic bacterial prostatitis (CBP) after a Stamey-meares (S-M) test for a period of 6 weeks and the test was repeated 1 and 6 months post therapy completion. 145 male patients presented for evaluation. the most prevalent symptoms included dysuria (68%), frequency (38%), and pain which was present in 50%. S-M testing was performed in 69% and expressed prostatic specimen was collected in 53.8%. the diagnosis of CBP was established in 26.9% of the total cohort. Escherichia coli (28.2%) and Enterococcus spp (23.1%) were the most frequently implicated pathogens and ciprofloxacin the most commonly prescribed antimicrobial. A 12-month follow-up was completed in 87% of the pts and 35.3% relapsed a mean of 4.75 months after the initial treatment.

Nationwide surveillance of Streptococcus pneumoniae in Greece: patterns of resistance and serotype epidemiology.

This nationwide study assessed the antimicrobial susceptibility and seroprevalence of Streptococcus pneumoniae in paediatric carriage isolates and in clinical isolates from adult pneumococcal disease in Greece during the years 2004-2006. Among 780 isolates recovered from the nasopharynx of children <6 years old attending day-care centres, non-susceptibility rates to penicillin, cefuroxime, ceftriaxone, erythromycin, tetracycline and trimethoprim/sulfamethoxazole were 34.7%, 25.1%, 1.0%, 33.5%, 26.4% and 44.2%, respectively. Among 89 adult clinical isolates, the respective rates were 48.3%, 46.1%, 5.6%, 48.3%, 32.6% and 40.4%. High-level resistance to penicillin, cefuroxime and ceftriaxone was recorded for 14.4%, 23.3% and 0.1% of paediatric carriage isolates, whereas for clinical adult isolates the respective rates were 25.8%, 38.2% and 2.2%. No resistance to levofloxacin and moxifloxacin was recorded, although 3.5% of paediatric carriage isolates and 23.2% of adult clinical isolates had minimum inhibitory concentrations of ciprofloxacin >2mg/L. Serotypes 19F, 14, 23F and 6B were the most prevalent among carriage and clinical isolates. The 7-valent pneumococcal conjugate vaccine was estimated to provide coverage against 71.7% of paediatric carriage isolates and 51.3% of adult clinical isolates. Resistance rates among clinical isolates from adult sources were higher than those recorded among paediatric carriage S. pneumoniae isolates and displayed an increasingly resistant profile compared with previous reports from our country, warranting continuous vigilance.

Efficacy and safety of an anti-retroviral combination regimen including either efavirenz or lopinavir-ritonavir with a backbone of two nucleoside reverse transcriptase inhibitors.

The efficacy and safety of a combination regimen including either efavirenz or lopinavir-ritonavir was examined in a cohort of 65 patients positive for human immunodeficiency virus-1 (HIV-1). Both the efavirenz (n = 33, 18 anti-retroviral naive) and lopinavir-ritonavir (n = 32, 15 naive) regimens achieved significant changes from baseline CD4 cell counts and HIV RNA levels after 108 weeks (p < 0.01). Despite diminished immunological and virological parameters at study entry, the lopinavir-ritonavir group showed greater virological effects than the efavirenz group after 108 weeks (median change 3.3 log(10), interquartile range (IQR) 2.2-3.8 log(10) vs. 2.4 log(10), IQR 0.9-3.3 log(10), respectively, p 0.004). Use of lopinavir-ritonavir, in contrast to use of efavirenz, was associated with significant hypertriglyceridaemia.

Evidence of less severe aortic valve destruction after treatment of experimental staphylococcal endocarditis with vancomycin and dexamethasone.

The beneficial effects of therapy combining an antibiotic and dexamethasone have been reported in human studies on meningitis and in experimental studies on septic arthritis, nephritis, and endophthalmitis. Since most patients with staphylococcal endocarditis need a combination of medical and surgical treatment, the purpose of this study was to determine whether the addition of dexamethasone to vancomycin has any beneficial effect regarding the degree of valve tissue damage or the course of experimental aortic valve endocarditis caused by a methicillin-resistant strain of Staphylococcus aureus. Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group and to groups receiving dexamethasone (0.5 mg/kg of body weight, intravenously [i.v.], twice a day [b.i.d]), vancomycin (30 mg/kg, i.v., b.i.d), or dexamethasone plus vancomycin, for a total of 10 doses (two doses per day for 5 days). The severity of valve tissue damage was significantly less in groups receiving vancomycin plus dexamethasone compared with that of the group receiving vancomycin alone (P < 0.001). The severity of tissue damage was inversely correlated with the mean polymorphonuclear leukocyte number in valve tissue. No statistically significant differences were observed between the vancomycin-treated group and the vancomycin-plus-dexamethasone-treated group in survival, blood culture sterilization rate, or reduction of the microbial burden (in CFU per gram) in valvular tissue. In conclusion, treatment with a combination of vancomycin and dexamethasone for 5 days reduces the severity of valve tissue damage in experimental staphylococcal aortic valve endocarditis. These findings could have significant implications in the treatment of staphylococcal endocarditis and deserve further confirmation in clinical trials.

Successful trovafloxacin prophylaxis against experimental streptococcal aortic valve endocarditis.

Single-dose trovafloxacin (15 mg/kg given intravenously [i.v.]) and ampicillin (40 mg/kg given i.v.) protected 38 and 33% of animals challenged with an ampicillin-tolerant strain of Streptococcus oralis, respectively. As a double-dose regimen, trovafloxacin afforded total protection (100%; P < 0.001 versus controls). Trovafloxacin is the first fluoroquinolone effective in preventing experimental streptococcal endocarditis.