Slovenia's national HIV PrEP programme: Evaluation of real-world implementation.

BACKGROUND: The aim of our study was to evaluate real-world implementation of Slovenia's national HIV PrEP programme, which is fully covered by our national health insurance. METHODS: In retrospective cohort study we analysed the data from all men who have sex with men (MSM) who were enrolled in PrEP programme of our clinic between 1 January 2022 and 31 December 2022. RESULTS: A total of 190 MSM with an average age of 36.7 years were included in our analysis. 151 (79.5%) decided for event-driven PrEP and 39 (20.5%) opted for daily PrEP. Self-reported adherence was 95%. Among eligibility criteria, unprotected sex was the most common one, followed by one or more STIs in the past, use of chemsex and use of HIV post-exposure prophylaxis in the past. No new cases of HIV infection and no significant deterioration of kidney or liver function were observed during the follow-up. Sixty-seven episodes of STIs were diagnosed and treated. Gonorrhea (32), chlamydia (14), and Mpox (10) were the most common ones. CONCLUSIONS: PrEP was successfully implemented into everyday clinical practice, proving to be both safe and effective. High number of diagnosed STIs suggests that the PrEP programme, combined with STI screening and vaccination, provides a strong public health impact among MSM in Slovenia.

Addressing HIV stigma in healthcare, community, and legislative settings in Central and Eastern Europe.

INTRODUCTION: Surging HIV prevalence across countries of Central and Eastern Europe (CEE) is largely a result of poor HIV care engagement and a lack of comprehensive support for key populations. This is fostered by widespread stigma across healthcare, community, and legislative settings. DISCUSSION: Throughout CEE, HIV stigma and intersectional stigma are serious obstacles to providing adequate medical care to people living with HIV. Anticipated and enacted (experienced) stigma from healthcare professionals, and fears of breaches in confidentiality, deter individuals from having an HIV test and engaging in HIV care. Furthermore, negative connotations surrounding HIV infection can lead to discrimination from family, friends, colleagues, and the public, leading to internalized stigma and depression. Key populations that have higher HIV prevalence, such as men who have sex with men, people who inject drugs, transgender individuals, and sex workers, experience additional stigma and discrimination based on their behaviour and identities. This contributes to the concentrated HIV epidemics seen in these populations in many CEE countries. The stigma is exacerbated by punitive legislation that criminalizes HIV transmission and penalizes sexual orientation, drug use, gender identities, and sex work. Despite high levels of HIV stigma and intersectional stigma, there are many evidence-based interventions that have reduced stigma in other parts of the world. Here, we discuss the interventions that are currently being enacted in various countries of CEE, and we suggest additional effective, evidence-based interventions that will tackle stigma and lead to increased HIV care engagement and higher rates of viral suppression. We cover the promotion of the undetectable = untransmittable (U = U) message, stigma-reduction education and training for healthcare professionals, patient-centric approaches for testing and treatment, and advocacy for non-discriminatory legislation, policies, and practices. We also consider targeted stigma-reduction interventions that acknowledge the wider challenges faced by marginalized populations. CONCLUSIONS: HIV stigma and intersectional stigma in CEE drive poor engagement with HIV testing services and care. Widespread adoption of evidence-based interventions to tackle stigma highlighted in this review will improve the quality of life of people living with HIV, improve HIV care engagement, and ultimately slow the surging HIV prevalence and concentrated epidemics occurring throughout CEE.

HIV-1 subtype diversity and phylogenetic insight into non-B subtype transmission in Slovenia, 1989-2013.

INTRODUCTION: Disease progression, drug resistance mutations, and treatment strategies may vary by HIV-1 subtype. This study determined HIV-1 subtypes circulating in Slovenia, a Central European country with an HIV-1 epidemic driven by men who have sex with men, focusing on molecular epidemiology of non-B subtypes. METHODS: A total of 367 HIV-1 sequences were included. Subtype was assigned by employing eight different HIV subtyping tools coupled with maximum likelihood phylogenetic analyses. RESULTS: The subtyping tools COMET, jpHMM, and REGA 3.0 exhibited the best performance on the dataset studied. Phylogenetic analyses showed a 14.7% prevalence of non-B subtypes, with subtype A detected most frequently (4.9%), followed by CRF02_AG (2.4%), subtype C (1.1%), subtypes D, G, and CRF01_AE (0.8% each), and subtypes F and CRF22_01A1 (0.3% each). A subtype could not be assigned to 12 sequences (3.3%), indicating potential unique recombinant forms. Non-B subtypes were significantly associated with a heterosexual route of transmission and infection acquired in Eastern Europe, Africa, or Asia. CONCLUSION: In a country where subtype B is predominant, non-B subtypes were observed in one out of seven patients, a non-negligible proportion, which underlines the importance of systematic surveillance of HIV subtype diversity and the corresponding molecular epidemiology.

PrEP Scale-Up and PEP in Central and Eastern Europe: Changes in Time and the Challenges We Face with No Expected HIV Vaccine in the near Future.

With no expected vaccine for HIV in the near future, we aimed to define the current situation and challenges for pre- and post-exposure prophylaxis (PrEP and PEP) in Central and Eastern Europe (CEE). The Euroguidelines CEE Network Group members were invited to respond to a 27-item survey including questions on PrEP (response rate 91.6%). PrEP was licensed in 68.2%; 95 centers offered PrEP and the estimated number on PrEP was around 9000. It was available in daily (40.1%), on-demand (13.3%), or both forms (33.3%). The access rate was <1−80%. Three major barriers for access were lack of knowledge/awareness among people who are in need (59.1%), not being reimbursed (50.0%), and low perception of HIV risk (45.5%). Non-occupational PEP was available in 86.4% and was recommended in the guidelines in 54.5%. It was fully reimbursed in 36.4%, only for accidental exposures in 40.9%, and was not reimbursed in 22.72%. Occupational PEP was available in 95.5% and was reimbursed fully. Although PrEP scale-up in the region has gained momentum, a huge gap exists between those who are in need of and those who can access PrEP. Prompt action is required to address the urgent need for PrEP scale-up in the CEE region.

The role of HIV/hepatitis B virus/hepatitis C virus RNA+ triple infection in end-stage liver disease and all-cause mortality in Europe.

BACKGROUND: There are limited data on end-stage liver disease (ESLD) and mortality in people with HIV (PWH) coinfected with both hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: All PWH aged greater than 18 under follow-up in EuroSIDA positive for HBsAg (HBV), and/or HCVRNA+, were followed from baseline (latest of 1 January 2001, EuroSIDA recruitment, known HBV/HCV status) to ESLD, death, last visit, or 31 December 2020. Follow-up while HCVRNA- was excluded. In two separate models, Poisson regression compared three groups updated over time; HIV/HBV, HIV/HCV, and HIV/HBV/HCV. RESULTS: Among 5733 included individuals, 4476 (78.1%) had HIV/HCV, 953 (16.6%) had HIV/HBV and 304 (5.3%) had HIV/HBV/HCV. In total, 289 (5%) developed ESLD during 34 178 person-years of follow-up (PYFU), incidence 8.5/1000 PYFU [95% confidence interval (CI) 7.5-9.4] and 707 deaths occurred during 34671 PYFU (incidence 20.4/1000 PYFU; 95% CI 18.9-21.9). After adjustment, compared with those with HIV/HCV, persons with HIV/HBV had significantly lower rates of ESLD [adjusted incidence rate ratio (aIRR) 0.53; 95% CI 0.34-0.81]. Those with HIV/HBV/HCV had marginally significantly higher rates of ESLD (aIRR 1.49; 95% CI 0.98-2.26). Those under follow-up in 2014 or later had significantly lower rates of ESLD compared with 2007-2013 (aIRR 0.65; 95% CI 0.47-0.89). Differences in ESLD between the three groups were most pronounced in those aged at least 40. After adjustment, there were no significant differences in all-cause mortality across the three groups. CONCLUSION: HIV/HBV-coinfected individuals had lower rates of ESLD and HIV/HBV/HCV had higher rates of ESLD compared with those with HIV/HCV, especially in those aged more than 40. ESLD decreased over time across all groups. CLINICALTRIALSGOV IDENTIFIER: NCT02699736.

The Management of HIV Care Services in Central and Eastern Europe: Data from the Euroguidelines in Central and Eastern Europe Network Group.

INTRODUCTION: The COVID-19 pandemic has been challenging time for medical care, especially in the field of infectious diseases (ID), but it has also provided an opportunity to introduce new solutions in HIV management. Here, we investigated the changes in HIV service provision across Central and Eastern European (CEE) countries before and after the COVID-19 outbreak. METHODS: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of ID from 24 countries within the CEE region. Between 11 September and 29 September 2021, the group produced an on-line survey, consisting of 32 questions on models of care among HIV clinics before and after the SARS-CoV-2 outbreak. RESULTS: Twenty-three HIV centers from 19 countries (79.2% of all countries invited) participated in the survey. In 69.5% of the countries, there were more than four HIV centers, in three countries there were four centers (21%), and in four countries there was only one HIV center in each country. HIV care was based in ID hospitals plus out-patient clinics (52%), was centralized in big cities (52%), and was publicly financed (96%). Integrated services were available in 21 clinics (91%) with access to specialists other than ID, including psychologists in 71.5% of the centers, psychiatrists in 43%, gynecologists in 47.5%, dermatologists in 52.5%, and social workers in 62% of all clinics. Patient-centered care was provided in 17 centers (74%), allowing consultations and tests to be planned for the same day. Telehealth tools were used in 11 centers (47%) before the COVID-19 pandemic outbreak, and in 18 (78%) after (p = 0.36), but were represented mostly by consultations over the telephone or via e-mail. After the COVID-19 outbreak, telehealth was introduced as a new medical tool in nine centers (39%). In five centers (28%), no new services or tools were introduced. CONCLUSIONS: As a consequence of the COVID-19 pandemic, tools such as telehealth have become popularized in CEE countries, challenging the traditional approach to HIV care. These implications need to be further evaluated in order to ascertain the best adaptations, especially for HIV medicine.

Olfactory evaluation in hospitalised and self-isolated patients with COVID-19: a single-centre experience on 55 cases.

BACKGROUND: Smell loss is a common symptom of COVID-19 infection. Majority of the studies that evaluated olfactory impairment in COVID-19 used questionnaires (subjective smell evaluations) and did not compare the results with objective or semiobjective measures of smell. We performed smell testing in hospitalised and self-isolated patients with COVID-19 and control participants. METHODS: Fifty-five COVID-19 and 44 control participants underwent smell testing, using Burghart Sniffin' Sticks 'Screening 12 Test'. Participants also rated their smelling capability on the numerical scale. Differences between groups and correlation between smell loss and time from acute onset of symptoms were tested, as well as correlation between results of smell test and subjective assessment of smell. RESULTS: Hospitalised patients with COVID-19 correctly determined 6.5/12 odorants compared with 10/12 in the self-isolated and 11/12 in the control group (p<0.001). Hyposmia or anosmia were present in 87.5% of hospitalised and 29.0% of self-isolated patients (p<0.001). The correlation between subjective self-assessment and results of smell testing was non-significant in both groups of patients with COVID-19, while there was a moderate positive correlation (p=0.001, Spearman's correlation coefficient=0.499) in control participants. CONCLUSION: Contrary to some previous reports suggesting that the presence of olfactory loss may predict milder course of disease, our study found that a vast majority of hospitalised patients with COVID-19 had prominent olfactory impairment. The absence of correlation between self-rated and objective smell evaluation in patients with COVID-19 indicates that subjective smell assessment is unreliable.

National strategies for vaccination against COVID-19 in people living with HIV in Central and Eastern European region.

INTRODUCTION: People living with HIV (PLWH) are at higher risk of poorer COVID-19 outcomes. Vaccination is a safe and effective method of prevention against many infectious diseases, including COVID-19. Here we investigate the strategies for national COVID-19 vaccination programmes across central and eastern Europe and the inclusion of PLWH in vaccination programmes. METHODS: The Euroguidelines in Central and Eastern Europe Network Group consists of experts in the field of infectious diseases from 24 countries in the region. Between 1 November 2020 and 19 March 2021 the group proceeded an on-line survey consisting of 20 questions. RESULTS: Twenty-two countries (out of 24 invited) participated in the survey and 20/22 countries in the period between December 2020 and March 2021 had already started their COVID-19 vaccination programme. In total, seven different vaccines were used by participating countries. In 17/21 countries (81%), vaccinated persons were centralized within the national registry. In 8/21 countries (38%) PLWH were prioritized for vaccination (the Czech Republic, Greece, Hungary, Lithuania, Montenegro, Romania, Slovakia, Slovenia) and the Czech Republic, Greece and Serbia had put in place national guidelines for vaccination of PLWH. In 14/20 countries (70%) vaccination was only provided by designated centres. Eighteen respondents (18/21; 85.7%) reported that they planned to follow up HIV patients vaccinated against COVID-19, mainly by measuring antibody levels and checking COVID-19 incidence (11/21; 52.3%). CONCLUSIONS: This survey-based study suggests that there are significant differences in terms of prioritizing PLWH, the types of vaccines used, vaccination coverage, and the development and implementation of a vaccination programmes within the region. Regardless of heterogenicity and existing barriers within the region, systematic vaccination in PLWH should have the highest priority, especially in those with severe immunodeficiency, risk factors, and in the elderly, aiming for prompt and high vaccination coverage.

Upregulated Intrathecal Expression of VEGF-A and Long Lasting Global Upregulation of Proinflammatory Immune Mediators in Vaccine Breakthrough Tick-Borne Encephalitis.

Although anti-TBE vaccines are highly effective, vaccine breakthrough (VBT) cases have been reported. With increasing evidence for immune system involvement in TBE pathogenesis, we characterized the immune mediators reflecting innate and adaptive T and B cell responses in neurological and convalescent phase in VBT TBE patients. At the beginning of the neurological phase, VBT patients have significantly higher serum levels of several innate and adaptive inflammatory cytokines compared to healthy donors, reflecting a global inflammatory state. The majority of cytokines, particularly those associated with innate and Th1 responses, are highly concentrated in CSF and positively correlate with intrathecal immune cell counts, demonstrating the localization of Th1 and proinflammatory responses in CNS, the site of disease in TBE. Interestingly, compared to unvaccinated TBE patients, VBT TBE patients have significantly higher CSF levels of VEGF-A and IFN-ß and higher systemic levels of neutrophil chemoattractants IL-8/CXCL8 and GROα/CXCL1 on admission. Moreover, serum levels of IL-8/CXCL8 and GROα/CXCL1 remain elevated for two months after the onset of neurological symptoms, indicating a prolonged systemic immune activation in VBT patients. These findings provide the first insights into the type of immune responses and their dynamics during TBE in VBT patients. An observed systemic upregulation of neutrophil derived inflammation in acute and convalescent phase of TBE together with highly expressed VEGF-A could contribute to BBB disruption that facilitates the entry of immune cells and supports the intrathecal localization of Th1 responses observed in VBT patients.

Pre-exposure prophylaxis for HIV with oral tenofovir disoproxil fumarate/emtricitabine in men who have sex with men: Slovenian national demonstration project.

Prevalence of HIV in Slovenia is low, and men who have sex with men (MSM) have the highest risk for infection. Rates of enrolment into HIV care, initiation of antiretroviral therapy and reaching an undetectable viral load in HIV-infected patients are very high. Prevention of HIV infection for MSM with PrEP is not formally available in Slovenia. The aim of this study was to demonstrate possible implementation of PrEP in Slovenia. Sixty-nine (n = 69) MSM with increased risk for HIV received PrEP with oral tenofovir disproxil fumarate /emtricitabine and acquisition were followed for a mean of 566.6 days. They had 71 episodes of STIs (incidence 61.7 per 100 person-years). No one got acquired HIV infection. Estimated glomerular filtration rate (EGFR) was significantly lower 4 (p = 0.014) and 19 (p = 0.021) months after inclusion; however, there was no clinically significant renal failure (mean EGFR 110-115 mL/min). Self-reported body weight significantly increased after 7 months (p < 0.05). Overall EGFR and self-reported body weight did not change significantly. No significant change in adherence (overall mean 81.0%; 95% CI 77.5%-84.6%; p = 0.728), condom use (p = 0.077) and number of sexual partners (overall mean 2.36 per 30 days; 95% CI 2.06 to 2.65; p = 0.235) was found throughout the study. Participants reported 110 graded adverse effects (AE), 104 (94.5%) grade 1-2 and 6 (5.5%) grade 3-4. No participant discontinued PrEP due to AE. The study showed successful implementation of PrEP among MSM at high risk for HIV infection in Slovenia. Based on the results of our study, PrEP should be formally available in Slovenia.

Influence of hepatitis C virus co-infection and hepatitis C virus treatment on risk of chronic kidney disease in HIV-positive persons.

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study. METHODS: HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m] between HCV strata. RESULTS: Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results. CONCLUSION: This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.

HIV-1 transmitted drug resistance in Slovenia and its impact on predicted treatment effectiveness: 2011-2016 update.

HIV-positive individuals that have a detected transmitted drug resistance (TDR) at baseline have a higher risk of virological failure with antiretroviral therapy (ART). This study offers an update on the prevalence of TDR in Slovenia, looks for onward transmission of TDR, and reassesses the need for baseline drug resistance testing. Blinded questionnaires and partial pol sequences were obtained from 54.5% (168/308) of all of the patients diagnosed with HIV-1 from 2011 to 2016. Subtype B was detected in 82.7% (139/168) of patients, followed by subtype A (8.3%), subtype C (2.4%), and CRF01_AE (1.8%). Surveillance drug resistance mutations (SDRMs) were found in four individuals (2.4%), all of them men who have sex with men (MSM) and infected with subtype B. K103N was detected in two patients and T68D and T215D in one person each, corresponding to a prevalence of 0%, 1.2%, and 1.2% of TDR to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs), respectively. The impact of mutations on drug susceptibility was found to be most pronounced for NNRTIs. No forward spread of TDR within the country was observed; however, phylogenetic analysis revealed several new introductions of HIV into Slovenia in recent years, possibly due to increased risky behavior by MSM. This was indirectly confirmed by a substantial increase in syphilis cases and HIV-1 non-B subtypes during the study period. A drug-resistant HIV variant with good transmission fitness is thus more likely to be imported into Slovenia in the near future, and so TDR should be closely monitored.

Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort.

BACKGROUND: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. METHODS: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed. RESULTS: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis. CONCLUSIONS: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

Very recent HIV infection accompanied by Pneumocystis jirovecii pneumonia and Mycobacterium avium complex immune reconstitution inflammatory syndrome: a case report.

A small proportion of HIV-infected patients rapidly progress to AIDS; indeed, some individuals have been known to progress to AIDS within a year after primary infection. Pneumonia caused by Pneumocystis jirovecii (PCP) is the most frequent AIDS-defining illness. However, PCP can also rarely occur during primary HIV infection as a result of the severe immunosuppression that may accompany the early stage of HIV infection. Immune reconstitution inflammatory syndrome (IRIS) comprises two distinct syndromes: paradoxical IRIS and unmasking IRIS. Infections with Mycobacterium avium complex during antiretroviral therapy are almost always localized and related to IRIS. We describe an unusual case of PCP and Mycobacterium avium complex-IRIS that occurred less than 3 months after primary HIV infection.

HIV resistance testing and detected drug resistance in Europe.

OBJECTIVES: To describe regional differences and trends in resistance testing among individuals experiencing virological failure and the prevalence of detected resistance among those individuals who had a genotypic resistance test done following virological failure. DESIGN: Multinational cohort study. METHODS: Individuals in EuroSIDA with virological failure (>1 RNA measurement >500 on ART after >6 months on ART) after 1997 were included. Adjusted odds ratios (aORs) for resistance testing following virological failure and aORs for the detection of resistance among those who had a test were calculated using logistic regression with generalized estimating equations. RESULTS: Compared to 74.2% of ART-experienced individuals in 1997, only 5.1% showed evidence of virological failure in 2012. The odds of resistance testing declined after 2004 (global P < 0.001). Resistance was detected in 77.9% of the tests, NRTI resistance being most common (70.3%), followed by NNRTI (51.6%) and protease inhibitor (46.1%) resistance. The odds of detecting resistance were lower in tests done in 1997-1998, 1999-2000 and 2009-2010, compared to those carried out in 2003-2004 (global P < 0.001). Resistance testing was less common in Eastern Europe [aOR 0.72, 95% confidence interval (CI) 0.55-0.94] compared to Southern Europe, whereas the detection of resistance given that a test was done was less common in Northern (aOR 0.29, 95% CI 0.21-0.39) and Central Eastern (aOR 0.47, 95% CI 0.29-0.76) Europe, compared to Southern Europe. CONCLUSIONS: Despite a concurrent decline in virological failure and testing, drug resistance was commonly detected. This suggests a selective approach to resistance testing. The regional differences identified indicate that policy aiming to minimize the emergence of resistance is of particular relevance in some European regions, notably in the countries in Eastern Europe.

Longitudinal trends of recent HIV-1 infections in Slovenia (1986-2012) determined using an incidence algorithm.

Resolving dilemma whether the rise in the number of HIV diagnoses represents an actual increase in HIV transmissions or is a result of improved HIV surveillance is crucial before implementing national HIV prevention strategies. Annual proportions of recent infections (RI) among newly diagnosed persons infected with HIV-1 in Slovenia during 27 years (1986-2012) were determined using an algorithm consisting of routine baseline CD4 and HIV viral load measurements and the Aware BED EIA HIV-1 Incidence Test (BED test). The study included the highest coverage of persons diagnosed with HIV during the entire duration of an HIV epidemic in a given country/region (71%). Out of 416 patients, 170 (40.9%) had a baseline CD4 cell count less than 200 cells/mm(3) and/or HIV-1 viral load less than 400 copies/ml and were characterized as having a long-standing infection (LSI). The remaining 246 patients were additionally tested using the BED test. Overall, 23% (97/416) of the patients were labeled RI. The characteristics significantly associated with RI were as follows: younger age, acute retroviral syndrome, CDC class A and other than C, no AIDS defining illnesses, HIV test performed in the past, a higher viral load, and a higher CD4 cell count. An interesting trend in the proportion of RI was observed, with a peak in 2005 (47% of RI) and the lowest point in 2008 (12%) in parallel with a rise in the numbers of new HIV diagnoses. This study could help promote the idea of introducing periodic HIV incidence monitoring using a simple and affordable algorithm.

Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.

A 57-year-old woman, receiving TNF-alpha inhibitor adalimumab for psoriasis, presented with early Lyme neuroborreliosis (Bannwarth's syndrome). Discontinuation of adalimumab and 14-day therapy with ceftriaxone resulted in a smooth course and favorable outcome of Lyme borreliosis. This is the first report on Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.

Bridging epidemiology with population genetics in a low incidence MSM-driven HIV-1 subtype B epidemic in Central Europe.

BACKGROUND: The HIV-1 epidemic in Slovenia, a small Central European country, has some characteristics that make it an ideal model to study HIV-1 transmission. The epidemic is predominantly affecting men who have sex with men infected with subtype B (89% of all patients), has a low prevalence (less than 1/1000) and is growing slowly. The aim of the present study was to analyze in detail the evolutionary history and the determinants of transmission. METHODS: A total of 223 partial pol gene sequences from therapy naïve individuals were included, representing 52% of all patients newly diagnosed in 13 years (2000-2012) and analyzed together with genetically similar worldwide sequences, selected in a BLAST search. RESULTS: Combined analysis (maximum likelihood and Bayesian) of HIV-1 transmission chains revealed 8 major clusters (n ≥ 10 patients), 1 group of 4 patients, 2 trios and 12 transmission pairs, thus leaving only 43 (19.3%) Slovenian patients infected with subtype B without a local epidemiological link, indicating a predominance of local transmission of HIV-1 infection. Bayesian analysis performed on a full set of sequences estimated several introductions of HIV-1 into Slovenia, with the most recent common ancestor (tMRCA) of the earliest Slovenian cluster dated to the late 1980s, although tMRCAs obtained from separate independent analysis of each cluster showed considerably more recent estimates. These findings indicate inconsistencies in molecular clock estimation, which we further explored. We hypothesize that these inconsistent dating estimates across the tree could be caused by an evolutionary rate acceleration of HIV-1 after entering the Slovenia epidemic that is not taken into account by the molecular clock model. It could be caused by a lower transmission rate in this setting, as demonstrated by the low epidemic growth rate estimated by Bayesian skyline plot analysis. CONCLUSIONS: HIV-1 subtype B was introduced into Slovenia at several time points from the late 80s onward. The majority of patients had a local transmission link, indicating a closed HIV community. The observed slower epidemic rate suggests that individuals with a long-lasting infection are the driving force of the epidemic in this region.

Cardiovascular risk assessment in HIV-infected male patients: a comparison of Framingham, SCORE, PROCAM and DAD risk equations.

INTRODUCTION: Traditional cardiovascular (CVD) risk assessment algorithms such as the Framingham Risk Score (FRS), Systematic Coronary Risk Evaluation (SCORE) and Prospective Cardiovascular Munster (PROCAM) were developed for general populations, their usefulness in HIV-infected population has not been confirmed. DAD algorithm was developed specifically for HIV-infected patients. The aim of our study was to evaluate the performance of risk assessment algorithms in HIV-infected population. METHODS: A prospective cross-sectional national study that included 83 HIV-infected male patients from Slovenia below the age of 55 was performed. CVD risk was assessed using four algorithms, the presence of subclinical atherosclerosis was determined by measuring carotid intima-media thickness (CIMT); patients were followed up for 5 years. RESULTS: High proportion of patients with low CVD risk according to FRS (61.9%) and PROCAM (81.0%) and only 7.1% according to SCORE had evidence of subclinical atherosclerosis. Only 7.1% of patients with low CVD risk according to DAD algorithm had evidence of subclinical atherosclerosis. CONCLUSION: Our study has shown that SCORE and DAD algorithm were superior to FRS and PROCAM. In younger HIV-infected patients, even with moderate CVD risk, CIMT assessment should be employed in a complete clinical evaluation as a more aggressive prevention and treatment approach is warranted.

Relationship between markers of endothelial dysfunction and inflammation and subclinical atherosclerosis in HIV-infected male patients below 55 years of age.

INTRODUCTION: Antiretroviral therapy in HIV-infected patients appears to be associated with increased incidence of cardiovascular disease (CVD).The aim of our study was to investigate the differences in markers of inflammation, endothelial dysfunction and prothrombotic state between treated and untreated HIV-infected patients with or without subclinical atherosclerosis. METHODS: Eighty-six Slovenian HIV-infected male patients below the age of 55 participated in our study. Levels of high-sensitivity C-reactive protein (hsCRP), vascular cell adhesion molecule 1 (VCAM-1) and plasminogen activator inhibitor 1 (PAI-1) were measured. The presence of subclinical atherosclerosis was determined by measuring carotid intima-media thickness. RESULTS: The level of hsCRP was significantly increased in HIV-infected patients; it was higher in treated than untreated patients. VCAM-1 was significantly increased; it was higher in untreated than treated patients. PAI 1 was significantly increased; there were no differences between untreated and treated patients. Patients with subclinical atherosclerosis had elevated hsCRP; levels of VCAM-1 and PAI-1 were not significantly different. CONCLUSION: Signs of systemic and vascular inflammation persist in both untreated and treated HIV infected patients. None of the studied markers contributed to improved assessment of subclinical atherosclerosis. The usefulness of such markers in routine clinical evaluation of CVD risk in HIV infected patients remains unclear.