A cross-sectional assessment of frailty, falls and perceptions of ageing in people living with HIV using an mHealth platform.

OBJECTIVE: To evaluate frailty, falls and perceptions of ageing among clinically stable individuals with HIV, engaged with remote healthcare delivered via a novel smartphone application. METHODS: This was a multi-centre European cross-sectional, questionnaire-based sub-study of EmERGE participants. Frailty was assessed using the five-item FRAIL scale. Present criteria were summed and categorized as follows: 0, robust; 1-2, pre-frail; 3-5, frail. Falls history and EQ-5D-5L quality of life measure were completed. Participants were asked their felt age and personal satisfaction with ageing. RESULTS: A total of 1373 participated, with a mean age of 45 (± 9.8) years. Frailty was uncommon at 2%; 12.4% fell in the previous year, 58.8% of these recurrently. Mood symptoms and pain were prevalent, at 43.3% and 31.8%, respectively. Ageing satisfaction was high at 76.4%, with 74.6% feeling younger than their chronological age; the mean felt age was 39.3 years. In multivariable analysis, mood symptoms and pain were positively associated with frailty, falls and ageing dissatisfaction. An increase in pain severity and mood symptoms were respectively associated with 34% and 63% increased odds of pre-frailty/frailty. An increment in pain symptoms was associated with a 71% increase in odds of falling. Pain was associated with ageing poorly, as were mood symptoms, with odds of dissatisfaction increasing by 34% per increment in severity. CONCLUSIONS: Although uncommon, frailty, falls and ageing dissatisfaction were seen in a younger cohort with medically stable HIV infection using a remote care model, promoting screening as advocated by European guidelines. These were more common in those with pain or mood symptoms, which should be proactively managed in clinical care and explored further in future research.

HIV treatment strategies across Central, Eastern and Southeastern Europe: New times, old problems.

INTRODUCTION: In the last decade, substantial differences in the epidemiology of, antiretroviral therapy (ART) for, cascade of care in and support to people with HIV in vulnerable populations have been observed between countries in Western Europe, Central Europe (CE) and Eastern Europe (EE). The aim of this study was to use a survey to explore whether ART availability and therapies have evolved in CE and EE according to European guidelines. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group conducted two identical multicentre cross-sectional online surveys in 2019 and 2021 concerning the availability and use of antiretroviral drugs (boosted protease inhibitors [bPIs], integrase inhibitors [INSTIs] and nucleoside reverse transcriptase inhibitors [NRTIs]), the introduction of a rapid ART start strategy and the use of two-drug regimens (2DRs) for starting or switching ART. We also investigated barriers to the implementation of these strategies in each region. RESULTS: In total, 18 centres participated in the study: four from CE, six from EE and eight from Southeastern Europe (SEE). Between those 2 years, older PIs were less frequently used and darunavir-based regimens were the main PIs (83%); bictegravir-based and tenofovir alafenamide-based regimens were introduced in CE and SEE but not in EE. The COVID-19 pandemic did not significantly interrupt delivery of ART in most centres. Two-thirds of centres adopted a rapid ART start strategy, mainly in pregnant women and to improve linkage of care in vulnerable populations. The main obstacle to rapid ART start was that national guidelines in several countries from all three regions did not support such as strategy or required laboratory tests first; an INSTI/NRTI combination was the most commonly prescribed regimen (75%) and was exclusively prescribed in SEE. 2DRs are increasingly used for starting or switching ART (58%), and an INSTI/NRTI was the preferred regimen (75%) in all regions and exclusively prescribed in SEE, whereas the use of bPIs declined. Metabolic disorders and adverse drug reactions were the main reasons for starting a 2DR; in the second survey, HIV RNA <500 000 c/ml and high cluster of differentiation (CD)-4 count emerged as additional important reasons. CONCLUSIONS: In just 2 years and in spite of the emergence of the COVID-19 pandemic, significant achievements concerning ART availability and strategies have occurred in CE, EE and SEE that facilitate the harmonization of those strategies with the European AIDS Clinical Society guidelines. Few exceptions exist, especially in EE. Continuous effort is needed to overcome various obstacles (administrative, financial, national guideline restrictions) in some countries.

Retrospective evaluation of an observational cohort by the Central and Eastern Europe Network Group shows a high frequency of potential drug-drug interactions among HIV-positive patients receiving treatment for coronavirus disease 2019 (COVID-19).

OBJECTIVES: The aim of this international multicentre study was to review potential drug-drug interactions (DDIs) for real-life coadministration of combination antiretroviral therapy (cART) and coronavirus disease 2019 (COVID-19)-specific medications. METHODS: The Euroguidelines in Central and Eastern Europe Network Group initiated a retrospective, observational cohort study of HIV-positive patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data were collected through a standardized questionnaire and DDIs were identified using the University of Liverpool's interaction checker. RESULTS: In total, 524 (94.1% of 557) patients received cART at COVID-19 onset: 117 (22.3%) were female, and the median age was 42 (interquartile range 36-50) years. Only 115 (21.9%) patients were hospitalized, of whom 34 required oxygen therapy. The most frequent nucleoside reverse transcriptase inhibitor (NRTI) backbone was tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide (TAF) with lamivudine or emtricitabine (XTC) (79.3%) along with an integrase strand transfer inhibitor (INSTI) (68.5%), nonnucleoside reverse transcriptase inhibitor (NNRTI) (17.7%), protease inhibitor (PI) (13.7%) or other (2.5%). In total, 148 (28.2%) patients received COVID-19-specific treatments: corticosteroids (15.7%), favipiravir (7.1%), remdesivir (3.1%), hydroxychloroquine (2.7%), tocilizumab (0.6%) and anakinra (0.2%). In total, 62 DDI episodes were identified in 58 patients (11.8% of the total cohort and 41.9% of the COVID-19-specific treatment group). The use of boosted PIs and elvitegravir accounted for 43 DDIs (29%), whereas NNRTIs were responsible for 14 DDIs (9.5%). CONCLUSIONS: In this analysis from the Central and Eastern European region on HIV-positive persons receiving COVID-19-specific treatment, it was found that potential DDIs were common. Although low-dose steroids are mainly used for COVID-19 treatment, comedication with boosted antiretrovirals seems to have the most frequent potential for DDIs. In addition, attention should be paid to NNRTI coadministration.

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.

REVERSIBILITY OF LIPOATROPHY IN HIV-INFECTED PATIENTS TAKING ANTIRETROVIRAL THERAPY: A COHORT STUDY WITH ULTRASOUND ASSESSMENT.

The aim of this study was to characterize and compare changes in subcutaneous fat in the malar, brachial and crural region in a cohort of HIV-infected patients taking antiretroviral therapy. This prospective longitudinal study included 77 patients who were selected from the initial cohort evaluated in 2007 and 2008. We examined reversibility of lipoatrophy measured by ultrasound over at least five-year period and factors related to its reversibility. All 46 patients who used stavudine switched from stavudine to another combination. Of 58 patients on zidovudine, 16 (28%) were on a zidovudine based regimen at the second follow up. There was evidence for subcutaneous fat increase in the malar area (p<0.001) and no increase in the brachial and crural areas. Patients who were smokers and had poor adherence to the Mediterranean diet had a thinner malar area at the follow up measurement (p=0.030) and smaller increase in subcutaneous malar fat compared to others (p=0.040). Our study suggested that modest increase of subcutaneous fat in malar area coincided with stopping stavudine and fewer usage of zidovudine. Lifestyle with non-adherence to the Mediterranean diet and smoking were associated with a smaller increase in subcutaneous malar fat.

The cost of care for people living with stable HIV in Croatia and the efficiency of EmERGE.

AIM: To estimate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV (PLHIV) at the University Hospital for Infectious Diseases (UHID), Zagreb. The Pathway includes a mobile application enabling individuals to communicate with their caregivers. METHODS: This study involving 293 participants collected data on the use of HIV outpatient services one year before and after EmERGE implementation. In departments supporting HIV outpatients, a micro-costing exercise was performed to calculate unit costs. These were combined with mean use of HIV services per patient year (MPPY) to estimate average annual costs. Primary outcomes were CD4 count, viral load, and secondary outcomes were patient activation, PAM13; and quality of life, PROQOL-HIV. Information on out-of-pocket expenditures was also collected. RESULTS: Outpatient visits decreased by 17%, from 4.0 (95% CI 3.8-4.3) to 3.3 MPPY (95% CI 3.1-3.5). Tests, including CD4 count, decreased, all contributing to a 33% reduction of annual costs: 7139 HRK (95% CI 6766-7528) to 4781 HRK (95% CI 4504-5072). Annual costs including anti-retroviral drugs (ARVs) decreased by 5%: 43101 HRK (95% CI 42728-43,490) to 40 743 HRK (95% CI 40466-41,034). ARVs remain the main cost driver in stable PLHIV. Primary and secondary outcomes did not change substantially between periods. CONCLUSION: EmERGE Pathway was a cost-saving intervention associated with changes in management, and a reduction in outpatient visits, tests, and costs. ARV costs dominated costs. Future efficiencies are possible if EmERGE is introduced to other PLHIV across the UHID and if ARV prices are reduced.

Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?

BACKGROUND: High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. METHODS: A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. RESULTS: We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. CONCLUSIONS: The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.

Substantial underdiagnosis of lymphogranuloma venereum in men who have sex with men in Europe: preliminary findings from a multicentre surveillance pilot.

OBJECTIVES: Understanding the public health impact of lymphogranuloma venereum (LGV) in Europe is hampered by inadequate diagnostics and surveillance systems in many European countries. We developed and piloted LGV surveillance in three European countries without existing systems and performed a preliminary investigation of LGV epidemiology, where little evidence currently exists. METHODS: We recruited STI or dermatovenereology clinics and associated laboratories serving men who have sex with men (MSM) in Austria, Croatia and Slovenia, using the UK for comparison. We undertook centralised LGV testing of Chlamydia trachomatis (CT)-positive rectal swabs collected between October 2016 and May 2017 from MSM attending these clinics. Stored specimens from Austria (2015-2016) and Croatia (2014) were also tested. Clinical and sociodemographic data were collected using a standardised proforma. The ompA gene of LGV-positive specimens was sequenced. RESULTS: In total, 500 specimens from CT-positive MSM were tested, and LGV positivity was 25.6% (128/500; 95% CI 22.0% to 29.6%) overall, and 47.6% (79/166; 40.1% to 55.2%) in Austria, 20.0% (3/15; 7.1% to 45.2%) in Croatia, 16.7% (1/6; 3.0% to 56.4%) in Slovenia and 14.4% (45/313; 10.9% to 18.7 %) in the UK. Proformas were completed for cases in Croatia, Slovenia and in the UK; proformas could not be completed for Austrian cases, but limited data were available from line listings. Where recorded, 83.9% (78/93) of LGV-CT cases were HIV-positive compared with 65.4% (149/228) of non-LGV-CT cases; MSM with LGV-CT were more likely to have proctitis (Austria, 91.8% vs 40.5%, p<0.001; Croatia, 100% vs 25%, p=0.04; UK, 52.4% vs 11.7%, p<0.001) than those with non-LGV-CT. Six different ompA sequences were identified, including three new variants; the L2 ompA sequence predominated (58.6%, 51/87). CONCLUSIONS: LGV is substantially underdiagnosed in MSM across Europe. Unified efforts are needed to overcome barriers to testing, establish effective surveillance, and optimise diagnosis, treatment and prevention.

Chlamydia trachomatis in Cervical Lymph Node of Man with Lymphogranuloma Venereum, Croatia, 20141.

We report an HIV-infected person who was treated for lymphogranuloma venereum cervical lymphadenopathy and proctitis in Croatia in 2014. Infection with a variant L2b genovar of Chlamydia trachomatis was detected in a cervical lymph node aspirate. A prolonged course of doxycycline was required to cure the infection.

The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection.

The aim of this study was to compare cytokine expression on both gene and protein levels in acute and chronic phase of HIV type 1 (HIV-1) infection. Thirty four patients were enrolled for cytokine expression analysis on protein level in acute and chronic stage of HIV-1 infection. Using PCR array technology, expression of 84 cytokine genes was measured in 3 patients in acute and 3 patients in chronic stage of HIV-1 infection. Bead-based cytometry was used to quantify levels of Th1/Th2/Th9/Th17/Th22 cytokines. The results showed statistically significant increase of 13 cytokine gene expression (cd40lg, csf2, ifna5, il12b, il1b, il20, lta, osm, spp1, tgfa, tnfsf 11, 14 and 8) and downregulation of the il12a expression in chronic HIV type 1 infection. Concentrations of IL-10, IL-4 and TNF-α were increased in the acute HIV type 1 infection when compared to control group. During chronic HIV type 1 infection there was an increase of IL-10, TNF-α, IL-2, IL-6, IL-13 and IL-22 levels when compared to control group. Comparison of cytokine expression between two stages of infection showed a significant decrease in IL-9 concentration. This study showed changes in cytokine profiles on both gene and protein levels in different stages of HIV-infection.

Effect of Extra Virgin Olive Oil on Biomarkers of Inflammation in HIV-Infected Patients: A Randomized, Crossover, Controlled Clinical Trial.

BACKGROUND: Premature atherosclerosis in HIV-infected patients is associated with chronic infection by itself and adverse effects of antiretroviral treatment (ART). Extra virgin olive oil (EVOO) has a beneficial effect on the cardiovascular system because of its anti-inflammatory properties. The objective of this study was to determine whether the consumption of EVOO improves inflammation and atherosclerosis biomarkers in HIV-infected patients receiving ART. MATERIAL AND METHODS: This randomized, crossover, controlled trial included 39 HIV-positive male participants who consumed 50 mL of EVOO or refined olive oil (ROO) daily. Four participants dropped out of the study. Leukocyte count, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), interleukin-6, fibrinogen, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde, glutathione-peroxidase, superoxide dismutase, oxidized LDL and von Willebrand factor were determined before the first and after each of the 2 intervention periods. Intervention and washout periods lasted for 20 and 14 days, respectively. RESULTS: In participants with >90% compliance (N=30), hsCRP concentrations were lower after EVOO intervention (geometric mean [GM], 1.70 mg/L; 95% confidence interval [CI], 1.15-2.52) compared to ROO administration (GM, 2.92 mg/L; 95% CI, 1.95-4.37) (p=0.035). In participants using lopinavir/ritonavir, ESR and hsCRP concentrations decreased 62% and 151%, respectively, after EVOO administration. In the whole study population (N=35) we found no difference in analyzed biomarkers after EVOO administration. CONCLUSIONS: Our exploratory study suggests that EVOO consumption could lower hsCRP in patients on ART.

Comparison of four international cardiovascular disease prediction models and the prevalence of eligibility for lipid lowering therapy in HIV infected patients on antiretroviral therapy.

AIM: To compare four cardiovascular disease (CVD) risk models and to assess the prevalence of eligibility for lipid lowering therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, European AIDS Clinical Society Guidelines (EACS), and European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS) guidelines for CVD prevention in HIV infected patients on antiretroviral therapy. METHODS: We performed a cross-sectional analysis of 254 consecutive HIV infected patients aged 40 to 79 years who received antiretroviral therapy for at least 12 months. The patients were examined at the HIV-treatment centers in Belgrade and Zagreb in the period February-April 2011. We compared the following four CVD risk models: the Framingham risk score (FRS), European Systematic Coronary Risk Evaluation Score (SCORE), the Data Collection on Adverse Effects of Anti-HIV Drugs study (DAD), and the Pooled Cohort Atherosclerotic CVD risk (ASCVD) equations. RESULTS: The prevalence of current smoking was 42.9%, hypertension 31.5%, and hypercholesterolemia (>6.2 mmol/L) 35.4%; 33.1% persons were overweight, 11.8% were obese, and 30.3% had metabolic syndrome. A high 5-year DAD CVD risk score (>5%) had substantial agreement with the elevated (≥7.5%) 10-year ASCVD risk equation score (kappa=0.63). 21.3% persons were eligible for statin therapy according to EACS (95% confidence intervals [CI], 16.3% to 27.4%), 25.6% according to ESC/EAS (95% CI, 20.2% to 31.9%), and 37.9% according to ACC/AHA guidelines (95% CI, 31.6 to 44.6%). CONCLUSION: In our sample, agreement between the high DAD CVD risk score and other CVD high risk scores was not very good. The ACC/AHA guidelines would recommend statins more often than ESC/EAS and EACS guidelines. Current recommendations on treatment of dyslipidemia should be applied with caution in the HIV infected population.

Mpox across countries from Central and Eastern Europe - 2022 outbreak.

BACKGROUND: The aim of the study was to assess socio-demographical characteristics, clinical presentation, and outcomes in patients diagnosed with mpox. METHODS: A survey on patients diagnosed with mpox was performed in 14 countries from Central and Eastern Europe. Data was compared according to HIV status and country of origin (EU vs. non-EU). Mpox diagnosis was confirmed by RT-PCR from oropharyngeal swabs, skin lesions, and other body fluids. RESULTS: Out of 154 patients confirmed with mpox in 2022, 99.3% were males, with a median age (years) of 35 (IQR 30-39), 90.2% MSM and 48.7% PLWH. Compared to HIV-negative subjects, PLWH had more frequent high-risk behaviours:chemsex (p = 0.015), group sex (p = 0.027), and a history of sexually transmitted infections (STIs) (p = 0.004). Persons from EU were more often PLWH (p = 0.042), MSM (p < 0.0001), had multiple sexual partners (p = 0.025), practiced chemsex (p = 0.008) or group-sex (p = 0.005) and had more often history of STIs (p < 0.0001). The median CD4 cell count/mL at mpox diagnosis was 713 (IQR 486-996) and 73.5% had undetectable HIV VL. The commonest clinical features were fever (108 cases), lymphadenopathy (78), and vesiculo-pustular rash: penile (76), perianal (48), limbs (67). Fifty-one (31%) persons were hospitalized due to complications or epidemiological reasons. Three patients received tecovirimat or cidofovir. The outcome was favorable for all patients, including 4 with severe forms. CONCLUSIONS: Mpox was diagnosed predominantly in young MSM, with high-risk behaviors and history of STIs. Effective contact tracing and vaccination are important strategic pillars to control mpox outbreaks.

Toxicity-related antiretroviral drug treatment modifications in individuals starting therapy: a cohort analysis of time patterns, sex, and other risk factors.

BACKGROUND: Modifications to combination antiretroviral drug therapy (CART) regimens can occur for a number of reasons, including adverse drug effects. We investigated the frequency of and reasons for antiretroviral drug modifications (ADM) during the first 3 years after initiation of CART, in a closed cohort of CART-naïve adult patients who started treatment in the period 1998-2007 in Croatia. MATERIAL AND METHODS: We calculated differential toxicity rates by the Poisson method. In multivariable analysis, we used a discrete-time regression model for repeated events for the outcome of modification due to drug toxicity. RESULTS: Of 321 patients who started CART, median age was 40 years, 19% were women, baseline CD4 was <200 cells/mm3 in 71%, and viral load was ≥100 000 copies/mL in 69%. Overall, 220 (68.5%) patients had an ADM; 124 (56%) of these had ≥1 ADM for toxicity reasons. Only 12.7% of individuals starting CART in the period 1998-2002 and 39.4% in the period 2003-2007 remained on the same regimen after 3 years. The following toxicities caused ADM most often: lipoatrophy (22%), gastrointestinal symptoms (20%), and neuropathy (18%). Only 5% of drug changes were due to virologic failure. Female sex (hazard ratio [HR], 2.42 95%; confidence intervals, 1.39-4.24) and older age (HR, 1.42 per every 10 years) were associated with toxicity-related ADM in the first 3 months of a particular CART regimen, but after 3 months of CART they were not. CONCLUSIONS: Less toxic and better-tolerated HIV treatment options should be available and used more frequently in Croatia.

Ultrasound measurements of carotid intima-media thickness and plaque in HIV-infected patients on the Mediterranean diet.

AIM: To evaluate the influence of food habits, specifically adherence to the Mediterranean diet, on carotid intima-media thickness (CIMT) and the presence of plaques in HIV-infected patients taking antiretroviral therapy (ART) and non-HIV-infected participants and to determine if HIV infection contributes independently to subclinical atherosclerosis. METHODS: We conducted a cross-sectional study of 110 HIV-infected patients on ART and 131 non-HIV-infected participants at the University Hospital for Infectious Diseases in Zagreb, Croatia, from 2009-2011. CIMT measurement and determination of carotid plaque presence was detected by ultrasound. Adherence to the Mediterranean diet was assessed by a 14-point food-item questionnaire. Subclinical atherosclerosis was defined by CIMT≥0.9 mm or ≥1 carotid plaque. RESULTS: In HIV-infected patients, subclinical atherosclerosis was associated with older age (Plt;0.001; Mann-Whitney test), higher body mass index (P=0.051; Mann-Whitney test), hypertension (Plt;0.001; χ(2) test), and a lower Mediterranean diet score (P=0.035; Mann-Whitney test), and in non-HIV-infected participants with older age (P lt; 0.001; Mann-Whitney test) and hypertension (P=0.006; χ(2) test). Multivariate analysis showed that decreased adherence to the Mediterranean diet was associated with higher odds of subclinical atherosclerosis (odds ratio [OR] 2.28, 95% confidence interval [CI] 1.10-4.72, P=0.027) as was current smoking (OR 2.86, 95% CI 1.28-6.40), hypertension (OR 3.04, 95% CI 1.41-6.57), and male sex (OR 2.35, 95% CI 0.97-5.70). There was a significant interaction of age and HIV status, suggesting that older HIV-infected patients had higher odds of subclinical atherosclerosis than controls (OR 3.28, 95% CI 1.24-8.71, P=0.017 at the age of 60 years). CONCLUSION: We confirmed the association between lower adherence to the Mediterranean diet and increased risk of subclinical atherosclerosis and found that treated HIV infection was a risk factor for subclinical atherosclerosis in older individuals.

Cryptococcus neoformans meningoencephalitis in a patient with idiopathic CD4+ T lymphocytopenia.

Cryptococcus neoformans is a leading cause of invasive cryptoccocal infections which include meningitis/meningoencephalitis, cerebral cryptococcoma, invasive pulmonary and mediastinal infection. Invasive infection is mainly diagnosed in immunocompromised patients, especially in HIV-infected individuals. There is a rising number of patients with invasive cryptococcal infections in immunocompromised patients who are HIV-negative. Among several primary immunodeficiency syndromes, considered as possible reasons for these invasive infections, idiopathic CD4+ T lymphocytopenia (ICL) is most frequently diagnosed. The pathogenesis of this rare syndrome is still unknown, while its clinical spectrum ranges from an asymptomatic laboratory abnormality to life-threatening opportunistic infections. Here we present an HIV-negative young man suffering from cryptococcal meningoencephalitis in whom ICL was diagnosed.

[Treatment of chronic hepatitis C in human immunodeficiency virus infected patients]. / Lijecenje kronicnog hepatitisa C u osoba zarazenih virusom humane imunodeficijencije.

Treatment of HCV infection offers the possibility of viral eradication, thus every person with a detectable HCV viral load is a candidate for treatment. Treatment is recommended to all HCV/HIV co-infected patients with: 1) repeatedly elevated aminotransferase levels; 2) F2 stage of liver fibrosis or higher, regardless of alanine aminotransferase values; and 3) more than 200 CD4+ lymphocytes per microL of blood. Treatment with a combination of pegylated interferon and weight-based ribavirin (1000 mg/day if < 75 kg and 1200 mg/day if > 75 kg) is recommended. Pegylated interferon is used as 180 microg for the alfa-2a form and 1.5 mg/kg for the alfa-2b form once weekly subcutaneously. HCV RNA should be measured after 4 weeks of treatment, and later as needed, in weeks 12, 24, 48 or 72. For evaluation of a sustained virologic response, HCV RNA should be measured 24 weeks after the end of treatment. Treatment duration for patients who have a rapid viral response (undetectable levels of HCV RNA after 4 weeks of treatment) is 24 weeks (genotypes 2 and 3) or 48 weeks (genotypes 1 and 4). For patients without a rapid virologic response, but with an adequate response after 12 and 24 weeks, we generally recommend treatment for 48 weeks. Treatment discontinuation is recommended for patients with < 2 log viral load decline after 12 weeks or with a detectable viral load after 24 weeks of treatment. In HCV genotype 1 infection and F3 or F4 liver fibrosis, treatment with boceprevir or telaprevir in addition to pegylated interferon and ribavirin is recommended. In case of persistent HCV replication during therapy stopping rules should be applied.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

Incidence, risk factors, and clinical findings of syphilis among men living with HIV in Croatia during the COVID-19 pandemic.

We conducted a nationwide longitudinal observational study to estimate the incidence of syphilis in a cohort of male persons living with HIV (MLWH) in Croatia in the pre-COVID-19 and COVID-19 years. Data were reviewed and extracted from the clinical database. We analyzed 1187 MLWH (≥ 18 years) in care in Croatia from 2018 to 2021 and used Poisson regression to calculate rates. We observed a 91.4% increase in incidence between 2019 and 2020; the overall rate was 6.0/100 person-years, and the annual rate ranged from 3.3/100 person-years in 2018 to 9.3/100 person-years in 2021. We found higher rates in men who have sex with men, MLWH with a baseline history of syphilis, MLWH with a more recent HIV diagnosis, and a lower rate in those who had clinical AIDS. The rate of syphilis serological testing was 3.5% lower in 2020 compared to 2019. Recurrent syphilis was more likely asymptomatic compared to the first episodes. In conclusion, during the COVID-19 epidemic years, there was a huge increase in syphilis. Results highlight the need for enhanced and novel prevention interventions.

Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022.

Molecular epidemiology of HIV-1 infection is challenging due to the highly diverse HIV-genome. We investigated the genetic diversity and prevalence of transmitted drug resistance (TDR) followed by phylogenetic analysis in 270 HIV-1 infected, treatment-naïve individuals from Croatia in the period 2019-2022. The results of this research confirmed a high overall prevalence of TDR of 16.7%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTIs (NNRTIs), and protease inhibitors (PIs) was found in 9.6%, 7.4%, and 1.5% of persons, respectively. No resistance to integrase strand-transfer inhibitors (INSTIs) was found. Phylogenetic analysis revealed that 173/229 sequences (75.5%) were part of transmission clusters, and the largest identified was T215S, consisting of 45 sequences. Forward transmission was confirmed in several clusters. We compared deep sequencing (DS) with Sanger sequencing (SS) on 60 randomly selected samples and identified additional surveillance drug resistance mutations (SDRMs) in 49 of them. Our data highlight the need for baseline resistance testing in treatment-naïve persons. Although no major INSTIs were found, monitoring of SDRMs to INSTIs should be continued due to the extensive use of first- and second-generation INSTIs.