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A. Cozzi-Lepri, L. Peters, A. Pelchen-Matthews, B. Neesgaard, S. De Wit, I. Johansen, S. Edwards, C. Stephan et al.

Introduction Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. Methods Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann–Whitney U test and Chi-square test. A logistic regression model was used to compare participants’ characteristics by treatment group. Kaplan–Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL). Results 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3–5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001). Conclusion Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS).

W. Bannister, T. Mast, S. De Wit, J. Gerstoft, L. Wiese, A. Milinkovic, V. Hadžiosmanović, A. Clarke et al.

Background: Weight gain is becoming increasingly prevalent amongst people with HIV (PWH) receiving contemporary antiretroviral treatment. We investigated BMI changes and clinical impact in a large prospective observational study. Methods: PWH aged ≥18 years were included who started a new antiretroviral (baseline) during 2010–2019 with baseline and ≥1 follow-up BMI assessment available. Rates of clinical outcomes (cardiovascular disease [CVD], malignancies, diabetes mellitus [DM] and all-cause mortality) were analysed using Poisson regression to assess effect of time-updated BMI changes (>1 kg/m2 decrease, ±1 kg/m2 stable, >1 kg/m2 increase), lagged by 1-year to reduce reverse causality. Analyses were adjusted for baseline BMI plus key confounders including antiretroviral exposure. Results: 6721 PWH were included; 72.3% were male, median age 48 years (interquartile range [IQR] 40–55). At baseline, 8.4% were antiretroviral-naive, and 5.0% were underweight, 59.7% healthy weight, 27.5% overweight, and 7.8% were living with obesity. There was an 8.2% increase in proportion of overweight and 4.8% in obesity over the study period (median follow-up 4.4 years [IQR 2.6–6.7]). 100 CVDs, 149 malignancies, 144 DMs, and 257 deaths were observed with incidence rates 4.4, 6.8, 6.6, 10.6 per 1000 person-years of follow-up, respectively. Compared to stable BMI, >1 kg/m2 increase was associated with increased risk of DM (adjusted incidence rate ratio [IRR]: 1.96, 95% confidence interval [CI]: 1.36–2.80) and >1 kg/m2 decrease with increased risk of death (adjusted IRR: 2.33, 95% CI: 1.73–3.13). No significant associations were observed between BMI changes and CVD or malignancies. Conclusions: A BMI increase was associated with DM and a decrease associated with death.

D. Raben, A. Sullivan, A. Mocroft, G. Kutsyna, V. Hadžiosmanović, A. Vassilenko, Nikoloz Chkhartisvili, V. Mitsura et al.

Background It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. Methods Individuals aged 18–65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015. Results Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5–3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. Conclusion The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.

Summary Background HIV infection is characterized by progressive depletion of CD4+ T cells due to their reduced synthesis and increased destruction followed by marked activation and expansion of CD8+ T lymphocytes. CD4/CD8 ratio was traditionally described as a marker of immune system ageing in the general population, but it increasingly appears as a marker of different outcomes in the HIV-infected population. The main objective of this study is to examine the power of CD4/CD8 ratio in predicting the occurrence of metabolic syndrome (MetS) in HIV-positive patients receiving cART therapy. Methods 80 HIV/AIDS subjects were included in a retrospective case-control study. Flow cytometry was used to determine the percentage of CD4+ and CD8+ cells in peripheral blood of these patients. The values of biochemical parameters (triglycerides, HDL, blood sugar, blood counts), immunological parameters (CD4/CD8, PCR), anthropometric measurements and type of cART therapy were evaluated in this study. Results After six months of cART therapy 19 (23.8%) subjects had all the elements necessary for making the diagnosis of MetS. Using multivariate analysis CD4/CD8 ratio was statistically significant (p < 0.05) and had the largest effect on development of MetS (Wald = 9.01; OR = 0.45), followed by cART (Wald = 7.87; OR = 0.10) and triglycerides (Wald = 5.27; OR = 1.7). On the other hand, body weight and waist circumference showed no statistically significant effect on the development of MetS after six months of cART, p > 0.05. Conclusions CD4/CD8 ratio proved to be a significant marker for prediction of metabolic syndrome in HIV/AIDS patients.

JR Santos, A. Cozzi-Lepri, A. Phillips, S. De Wit, C. Pedersen, P. Reiss, A. Blaxhult, A. Lazzarin et al.

A. Mocroft, K. Laut, P. Reiss, J. Gatell, V. Ormaasen, M. Cavassini, V. Hadžiosmanović, K. Mansinho et al.

A. Cozzi-Lepri, R. Zangerle, L. Machala, K. Zilmer, M. Ristola, C. Pradier, O. Kirk, H. Sambatakou et al.

There are currently few data on the long‐term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association.

D. Raben, A. Mocroft, M. Rayment, V. Mitsura, V. Hadžiosmanović, Z. Sthoeger, A. Palfreeman, S. Morris et al.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32–97), lowest in Northern Europe (median 44%, IQR 22–68%) and highest in Eastern Europe (median 99%, IQR 86–100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0–4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

D. Podlekareva, D. Grint, I. Karpov, A. Vassilenko, A. Rakmanova, K. Mansinho, N. Chentsova, E. Kravchenko et al.

A. Cozzi-Lepri, M. Noguera-Julián, Francesca Di Giallonardo, R. Schuurman, M. Däumer, S. Aitken, F. Ceccherini‐Silberstein, A. d’Arminio Monforte et al.

Objectives It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. Methods This Europe-wide case–control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%–25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. Results Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35–5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76–6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12–5.18, P = 0.024). A dose–effect relationship between virological failure and mutational load was found. Conclusions Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

A. Sullivan, D. Raben, J. Reekie, M. Rayment, A. Mocroft, S. Esser, A. León, J. Begovac et al.

Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009– February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% [95% CI: 1.42–2.34]; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe.

SUMMARY CONFLICT OF INTEREST: none declared. Introduction Brucella endocarditis (BE) is a rare but severe and potentially lethal manifestation of brucellosis. Pre-existing valves lesions and prosthetic valves (PV) are favorable for BE. Case report We represent the case of a 46-year-old man who was treated at the Clinic for Infectious Diseases, Clinical Center of Sarajevo University, as blood culture positive (Brucella melitensis) mitral and aortic PV endocarditis. He was treated with combined anti-brucella and cardiac therapy. Surgical intervention was postponed due to cardiac instability. Four months later he passed away. Surgery was not performed.

S. Mehanić, R. Baljić, V. Mulabdić, Ilhama Huric-Jusufi, F. Pinjo, Jasna Topalovic-Cetkovic, V. Hadžiosmanović

INTRODUCTION Osteoarticular manifestations of human brucellosis occur in 20-40% of patients while spondylodiscitis is the most severe form of the bone and joint structures involvements. AIM The aim of this paper is tho show clinical and radiological caracteristics of osteoarticular forms of brucellosis, with special reference to spondylodiscitis. MATERIAL AND METHODS The medical histories of 120 hospitalized patients at the Clinic for Infectious Diseases, Clinical Center of Sarajevo University, diagnosed with brucellosis, were analyzed. RESULTS Osteoarticular manifestations had sixty-nine patients, representing 78.4% of all localized forms of the disease. Spondylodiscitis represents 40.6% of all osteoarticular manifestations of the disease. Nine patients (32.1%) had paravertebral and paraspinal abscess. Median diagnostic interval for spondylodiscitis (116 +/- 160 days) was almost twice prolonged compared to the arthritis and sacroilitis (p < 0.05). The most common radiological manifestations were erosions of the vertebral surface (67.8%). Computerized tomography confirmed inflammation in 85.2% of the patients, while magnetic resonance imaging (MRI) showed radiological alterations in all patients (100%). DISCUSSION AND CONCLUSION Osteoarticular manifestations are the most common localised forms of brucellosis. The frequency of spondylodiscitis is in relation to duration of the diagnostic time. MRI shows a high degree of sensitivity to inflammatory changes of spine and "Pedro Pons' sign" is patognomic radiological alteration.

A. Sönnerborg, A. Mocroft, Jens D. Lundgren, D. Raben, Gatell Jm, A. Vassilenko, V. Hadžiosmanović, J. Bergovac et al.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

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