Josip Begovac

Feasibility and Effectiveness of Indicator Condition-Guided Testing for HIV: Results from HIDES I (HIV Indicator Diseases across Europe Study)

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.

European recommendations for the management of healthcare workers occupationally exposed to hepatitis B virus and hepatitis C virus

Exposure prevention is the primary strategy to reduce the risk of occupational bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made aware of the medicolegal and clinical relevance of reporting an exposure, and have ready access to expert consultants to receive appropriate counselling, treatment and follow-up. Vaccination against hepatitis B virus (HBV), and demonstration of immunisation before employment are strongly recommended. HCWs with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, >10 mIU/mL are considered as responders. Responders are protected against HBV infection: booster doses of vaccine or periodic antibody concentration testing are not recommended. Alternative strategies to overcome non-response should be adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBc IgM and HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between infection (anti-HBs >50 mUI/ml 30 days after 1st vaccination: anamnestic response) and false positive results(anti-HBs >10 mUI/ml 30 days after 3rd vaccination: primary response); true positive subjects have resistance to re-infection. and do not need vaccination The management of an occupational exposure to HBV differs according to the susceptibility of the exposed HCW and the serostatus of the source. When indicated, post-exposure prophylaxis with HBV vaccine, hepatitis B immunoglobulin or both must be started as soon as possible (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV) infection, follow-up management of HCV exposures depends on whether antiviral treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is recommended, perform ALT (amino alanine transferase) activity at baseline and monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is detected.

Asymptomatic pharyngeal carriage of beta-haemolytic streptococci and streptococcal pharyngitis among patients at an urban hospital in Croatia

In a one-year study at the University Hospital of Infectious Diseases in Zagreb, Croatia the rate of asymptomatic throat carriage of beta-haemolytic streptococci was investigated. Throat carriage was investigated in 1796 patients, none of whom had a sore throat nor signs and/or symptoms of a respiratory tract infection. The carrier rate of beta-haemolytic streptococci was 8.3%, for group A streptococci 6%, group B 1.3%, group C 0.3% and group F 0.1%. The highest rate was observed in the 6 to 14 year age group: 13.8% for all streptococcal groups, 11.7% for group A alone. The proportion of non-A streptococci was higher in older age groups. Tonsillectomised individuals were less frequently carriers. No sex or season-dependent variations were observed. In a four-month study of 629 patients with pharyngitis the throat cultures yielded: group A streptococci in 44.7%, group B in 1.7%, group C in 0.8%, and group G in 0.6% of the patients. Group A streptococcal rates in carriers compared to rates in patients with pharyngitis suggest that approximately one fourth of the schoolchildren with culture-positive pharyngitis actually are not truly infected, but only carriers currently having a sore throat of non-streptococcal etiology.Antibiotics were administrated to 605 (96.2%) patients with pharyngitis; in 571 (94.4%) of the cases before culture results became available. After culture-negative results were obtained the therapy was discontinued in only 28.5% of the cases. The throat culture is the standard for laboratory testing of group A streptococcal infection and should have more influence on the management of patients with pharyngitis at our hospital.

2014 European Guideline on HIV testing

Testing for HIV is one of the cornerstones in the fight against HIV spread. The 2014 European Guideline on HIV Testing provides advice on testing for HIV infection in individuals aged 16 years and older who present to sexually transmitted infection, genito-urinary or dermato-venereology clinics across Europe. It may also be applied in other clinical settings where HIV testing is required, particularly in primary care settings. The aim of the guideline is to provide practical guidance to clinicians and laboratories that within these settings undertake HIV testing, and to indicate standards for best practice.

Urinary tract infections in HIV disease.

HIV-positive patients are liable to acquire opportunistic infections. Their liability to acquire other common infectious conditions is less frequently reported. In order to determine the frequency of urinary tract infections (UTI) in HIV-positive patients, we performed a retrospective analysis. The control group was formed from patients with community acquired pneumonia. We reviewed charts of 96 HIV-positive patients and of 314 patients in the control study group. The analysis has shown that patients with HIV had a UTI more frequently than the controls. Besides the difference in the frequency, we observed the difference in the etiology. Enterococci were the most frequent isolates in patients with HIV disease, whereas Escherichia coli was most frequently isolated in the controls. These facts should be taken into consideration when treatment of a UTI with suspected bacteremia in AIDS patients is initiated.

Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

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.

Prevalence of Sexually Transmitted Infections Among Men Who Have Sex with Men in Zagreb, Croatia

We used respondent-driven sampling among men who have sex with men (MSM) in Zagreb, Croatia in 2006 to investigate the prevalence of HIV, other sexually transmitted infections and sexual behaviours. We recruited 360 MSM. HIV infection was diagnosed in 4.5%. The seroprevalence of antibodies to viral pathogens was: herpes simplex virus type-2, 9.4%; hepatitis A, 14.2%; hepatitis C, 3.0%. Eighty percent of participants were susceptible to HBV infection (HBs antigen negative, and no antibodies to HBs and HBc antigen). Syphilis seroprevalence was 10.6%. Prevalence of Chlamydia and gonorrhoea was 9.0%, and 13.2%, respectively. Results indicate the need for interventions to diagnose, treat and prevent sexually transmitted infections among this population.

Post-Exposure Prophylaxis of HIV Infection in Healthcare Workers: Recommendations for the European Setting

The European Commission funded a project for the standardisation of the management of occupational exposures to HIV/blood-borne infections and antiretroviral post-exposure prophylaxis (PEP) in Europe. Within this project, the following recommendations and rationale were formulated by experts representative of participating countries. Based on assessment of the exposure, material, and source characteristics, PEP should be started as soon as possible with any triple combination of antiretrovirals approved for the treatment of HIV-infected patients; initiation is discouraged after 72 hours Rapid HIV testing of the source could reduce inappropriate PEP. HIV testing should be performed at baseline, 4, 12, and 24 weeks, with additional clinical and laboratory monitoring of adverse reactions and potential toxicity at week 1 and 2. HIV resistance tests in the source and direct virus assays in the exposed HCW are not recommended routinely. These easy-to-use recommendations seek to maximise PEP effect while minimising its toxicity and inappropriate use.

A standardized algorithm for determining the underlying cause of death in HIV infection as AIDS or non-AIDS related: results from the EuroSIDA study.

Abstract Objectives: Analyzing changes in causes of death over time is essential for understanding the emerging trends in HIV population mortality, yet data on cause of death are often missing. This poses analytic limitations, as does the changing approach in data collection by longitudinal studies, which are a natural consequence of an increased awareness and knowledge in the field. To monitor and analyze changes in mortality over time, we have explored this issue within the EuroSIDA study and propose a standardized protocol unifying data collected and allowing for classification of all deaths as AIDS or non-AIDS related, including events with missing cause of death. Methods: Several classifications of the underlying cause of death as AIDS or non-AIDS related within the EuroSIDA study were compared: central classification (CC-reference group) based on an externally standardised method (the CoDe procedures), local cohort classification (LCC) as reported by the site investigator, and 4 algorithms (ALG) created based on survival times after specific AIDS events. Results: A total of 2,783 deaths occurred, 540 CoDe forms were collected, and 488 were used to evaluate agreements. The agreement between CC and LCC was substantial (κ = 0.7) and the agreement between CC and ALG was moderate (κ < 0.6). Consequently, a stepwise algorithm was derived prioritizing CC over LCC and, in patients with no information available, best-fit ALG. Using this algorithm, 1,332 (47.9%) deaths were classified as AIDS and 1,451 (52.1%) as non-AIDS related. Conclusions: Our proposed stepwise algorithm for classifying deaths provides a valuable tool for future research, however validation in another setting is warranted.

IAPAC guidelines for optimizing the HIV care continuum for adults and adolescents

Background: An estimated 50% of people living with HIV (PLHIV) globally are unaware of their status. Among those who know their HIV status, many do not receive antiretroviral therapy (ART) in a timely manner, fail to remain engaged in care, or do not achieve sustained viral suppression. Barriers across the HIV care continuum prevent PLHIV from achieving the therapeutic and preventive effects of ART. Methods: A systematic literature search was conducted, and 6132 articles, including randomized controlled trials, observational studies with or without comparators, cross-sectional studies, and descriptive documents, met the inclusion criteria. Of these, 1047 articles were used to generate 36 recommendations to optimize the HIV care continuum for adults and adolescents. Recommendations: Recommendations are provided for interventions to optimize the HIV care environment; increase HIV testing and linkage to care, treatment coverage, retention in care, and viral suppression; and monitor the HIV care continuum.