Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone turnover markers in HIV-infected patients

BACKGROUND: Osteoporosis and bone fractures seem to be higher in HIV-infected Patients compared to the general populations. Moreover, bone turnover markers are increased in patients on antiretroviral therapy and vitamin D deficiency is prevalent in HIV-infected patients. However, the influence of per oral cholecalciferol on bone metabolism in HIV infected patients is not well understood. METHODS: We measured the bone turnover markers in 96 HIV-infected patients: Bone specific alkaline phosphatase (BSAP), Pyridinoline (PYR), Desoxypyridinoline (DPD) and 25-OH vitamin D. If 25-OH vitamin D was below 75 nnol/L (87/96 patients), 300000 IU cholecalciferol was given per os. 25OH-vitamin D and bone turn over markers were determinded 3 month later. 25 OH-vitamin D was corrected for circannual rythm [Formula: see text] , whereas bone turnover markers were not corrected. The paired students t-Test was used to compare the two periods. No calcium supplementation or biphosphonate therapy was given. RESULTS: Corrected 25OH-vitamin D levels increased significantly after supplementation (42.7 ± 26.61 vs. 52.85 ± 21.8 nmol/L, p < 0.001). After supplementation, bone turnover markers were significantly lower. The values decreased for BSAP from 21.31 ± 14.32 to 17.53 ± 8.17 μg/L (p < 0.001), PYR from 74.57 ± 36.83 to 54.82 ± 21.43 nmol/mmol creatinine (p < 0.001) and DPD from 15.17 ± 8.34 to 12.61 ± 5.02 nmol/mmol creatinine (p = 0.01). CONCLUSIONS: After per oral substitution with cholecalciferol, bone formation as well as bone resorption markers decreased significant. We postulate a protective effect on bone structure with cholecalciferol supplementation

Hepatitis C virus elimination in Swiss opioid agonist therapy programmes - the SAMMSU cohort.

BACKGROUND Hepatitis C virus (HCV) infections in Switzerland are mainly related to intravenous drug use. Since 2017, all patients with chronic hepatitis C can be treated with direct-acting antivirals (DAAs) irrespective of fibrosis stage. In March 2019, the Federal Office of Public Health (FOPH) published guidelines for HCV management in people who use drugs. To achieve HCV elimination by 2030, 80% treatment uptake is necessary. AIM To evaluate the benefit of interferon-based and interferon-free HCV treatment in patients on opioid agonist therapy (OAT) and monitor HCV elimination, a 2-year study commissioned by the FOPH and conducted within the Swiss Association for the Medical Management in Substance Users (SAMMSU) cohort was performed. METHODS Since 2014, the SAMMSU cohort has recruited OAT patients from eight different centres throughout Switzerland. In addition to yearly follow up, cross-sectional data were collected at the time-points 1 May 2017, 1 May 2018 and 1 May 2019. HCV treatment uptake, adherence and success, as well as reinfection rates, the effect of early versus late treatment and the efficacy of the &ldquo;treatment-as-prevention&rdquo; approach were analysed. RESULTS Between 1 May 2017 and 1 May 2019, the number of patients enrolled into the SAMMSU cohort increased from 623 to 900: 78% were male, the median age was 45 years, 81% had ever used intravenous drugs, 13% were human immunodeficiency virus (HIV) positive and 66% were HCV antibody positive. HCV treatment up to 2012 was exclusively interferon based (maximum 21 patients/year) and since 2016 exclusively interferon free (102 patients in 2017). Treatment success increased from 57% (112/198; interferon based) to 97% (261/268; interferon free) irrespective of cirrhosis or prior non-response to interferon. Simultaneously, treatments became shorter and better tolerated in the interferon-free era, resulting in fewer preterm stops (17% vs 1%) and adherence problems (9% vs 2%). Between 2015 and 2018, the proportion of patients with no/mild fibrosis (F0/F1) at first HCV treatment increased from 0% to 61%. Earlier treatment reduced the duration of infectiousness. Between 1 May 2017 and 1 May 2019, the proportion of chronic hepatitis C patients ever treated increased from 62% (198/321) to 80% (391/490). In parallel, the HCV-RNA prevalence among HCV antibody-positive patients declined from 36% (139/385) to 19% (113/593). The reinfection rate after successful treatment was 2.7/100 person-years. The number of HCV first diagnoses per year decreased from &gt;20 up to 2015 to &lt;10 in 2017 and 2018. CONCLUSION With nearly 100% DAA treatment success and a low reinfection rate, treatment uptake directly translates into a reduction of HCV-RNA prevalence. Eighty percent treatment uptake is feasible in OAT patients, and adherence and treatment success are not worse than in other populations. Duration of infectiousness and thus HCV transmission can be reduced by early detection and treatment of chronic hepatitis C

Simple monitoring of antiretroviral therapy with a signal-amplification-boosted HIV-1 p24 antigen assay with heat-denatured plasma.

OBJECTIVE: Virus load determination has become indispensable for the management of HIV patients, but depends on expensive assays of a low throughput. We evaluated whether a highly improved HIV-1 p24 antigen detection procedure which involves heat-mediated immune complex dissociation and signal-amplification-boosted enzyme-linked immunosorbent assay (ELISA) was suitable for antiretroviral treatment monitoring. DESIGN AND METHODS: Virus load in plasma was determined for 127 plasma samples taken at 0, 2, 6, 12, 18, 24, 30 and 36 weeks from 23 patients with CD4+ T cells < 50 x 10(6)/l who received indinavir 800 mg three times daily in addition to prior antiretroviral treatment. Tests included polymerase chain reaction (PCR) for viral RNA, measured prospectively with the Roche Amplicor kit, and retrospective batch testing of heat-denatured samples for p24 antigen by the DuPont HIV-1 p24 Core Profile ELISA linked with a tyramide signal amplification step. Particle-associated reverse transcriptase (RT) by the product-enhanced RT (PERT) assay was determined as an independent third-opinion viral load marker. RESULTS: p24 antigen was detected as sensitively as viral RNA. Overall detection during a median observation time of 25 weeks (range, 0-39) amounted to 75.6% for antigen and 73.6% for RNA. The antigen detection limit was 0.2 pg/ml. Antigen was detectable in all 23 baseline samples, whereas RNA was undetectable in one. Antigen and RNA levels in 79 samples positive for both markers correlated with r = 0.714 (P < 0.0001). Average changes in levels of p24 antigen and RNA at eight timepoints correlated with r = 0.982 (P < 0.0001). In individual patients, the two parameters behaved similarly, and in certain cases virtually identically. RT activity was measurable in all samples. CONCLUSIONS: The performance of this antigen detection procedure is comparable to RNA PCR, thus providing a simple, high throughput alternative in monitoring the efficacy of antiretroviral treatment