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HIV bolest je kronični progresivni proces koji započinje ulaskom virusa humane imunodeficijencije u organizam, a ako se ne liječi u konačnici dovodi do uništavanja imunološkog sustava, oportunističkih infekcija i smrtnog ishoda. Antiretrovirusna terapija (ART) smanjuje morbiditet i mortalitet ovih bolesnika. Promjene ART-a događaju se zbog niza razloga, uključivo i toksičnost. Istražili smo učestalost i razloge promjena kod 732 bolesnika koji su započeli liječenje u Hrvatskoj u razdoblju od 1998. do 2013. i koje smo pratili tijekom prve 3 godine nakon započinjanja terapije. Podijelili smo ih u dvije skupine, oni koji su terapiju započeli između 1998. i 2005. te one koji su započeli između 2006. i 2013. te pronašli da među razdobljima postoje značajne razlike. U prvom razdoblju najčešći razlog promjena bio je toksičnost, dok u drugom razdoblju zbog primjene novijih i manje toksičnih lijekova toksičnost postaje manji problem pa kao razlog promjena prevladava odluka liječnika baš kako bi se spriječila toksičnost terapije. U multivarijatnoj analizi pokazalo se da starija dob, ženski spol te neki lijekovi (stavudin) i neke skupine antiretrovirusnih lijekova (inhibitori proteaze) povećavaju rizik za promjenu terapije zbog toksičnosti. U konačnici većina naših opažanja slična je podacima iz istraživanja u razvijenim zemljama iako se zbog razlika u primjeni nekih lijekova drugdje i u Hrvatskoj određena razdoblja ne mogu adekvatno usporediti. Važno je imati na umu da su mnogi stariji lijekovi povezani s većom toksičnošću i da usprkos povećanim troškovima za liječenje osoba zaraženih HIV-om trebamo težiti najoptimalnijim kombinacijama lijekova za naše bolesnike., Infection with Human Immunodeficiency virus (HIV) is chronic, progressive disease which starts when HIV enters the organism. If not treated this condition leads to collapse of immunologic system, opportunistic infections and death. Introduction of antiretroviral therapy (ART) dramatically changed the prognosis of these patients. Modifications to ART regimens can occur for a number of reasons, including adverse effects. We have investigated the reasons and the frequency of ART modifications during the first 3 years after initiation of ART among 732 adult patients who started treatment in the period 1998-2013 in Croatia. We divided the patients in two groups: those who started ART between 1998 and 2005 and those who started ART between 2006 and 2013 and we found significant differences between periods. In the first period the most frequent reason for modification of ART were adverse effects and in the second one it was the decision of the physician guided by the prevention of adverse effects. Older age, female sex and certain drugs (stavudine) and drug classes (protease inhibitors) were significantly associated with the modification of the therapy due to adverse effects. Our findings were similar to many studies who analysed the same period. Less toxic and better-tolerated treatments should be available and used in Croatia in order to optimize the therapy.

Objectives\ud Despite successful treatment, people living with HIV experience persisting and burdensome multidimensional problems. We aimed to assess the validity, reliability and responsiveness of Positive Outcomes, a patient-reported outcome measure for use in clinical practice.\ud \ud Methods\ud In all, 1392 outpatients in five European countries self-completed Positive Outcomes, PAM-13 (patient empowerment), PROQOL-HIV (quality of life) and FRAIL (frailty) at baseline and 12 months. Analysis assessed: (a) validity (structural, convergent and divergent, discriminant); (b) reliability (internal consistency, test-retest); and (c) responsiveness.\ud \ud Results\ud An interpretable four-factor structure was identified: ‘emotional wellbeing’, ‘interpersonal and sexual wellbeing’, ‘socioeconomic wellbeing’ and ‘physical wellbeing’. Moderate to strong convergent validity was found for three subscales of Positive Outcomes and PROQOL (ρ = −0.481 to −0.618, all p < 0.001). Divergent validity was found for total scores with weak ρ (−0.295, p < 0.001). Discriminant validity was confirmed with worse Positive Outcomes score associated with increasing odds of worse FRAIL group (4.81-fold, p < 0.001) and PAM-13 level (2.28-fold, p < 0.001). Internal consistency for total Positive Outcomes and its factors exceeded the conservative α threshold of 0.6. Test-retest reliability was established: those with stable PAM-13 and FRAIL scores also reported median Positive Outcomes change of 0. Improved PROQOL-HIV score baseline to 12 months was associated with improved Positive Outcomes score (r = −0.44, p < 0.001).\ud \ud Conclusions\ud Positive Outcomes face and content validity was previously established, and the remaining validity, reliability and responsiveness properties are now demonstrated. The items within the brief 22-item tool are designed to be actionable by health and social care professionals to facilitate the goal of person-centred care.

HIV pre-exposure prophylaxis (PrEP) is a medical intervention with the antiretroviral drug(s) used as prophylaxis in order to achieve high level of protection against HIV infection. It does not protect against other sexually transmitted infections (STI) though. Therefore, PrEP should be supervised by a doctor, experienced with STI and antiretroviral drugs. Documented negative HIV test (4th generation HIV test or even molecular test) is obligatory prior to starting PrEP. In Europe PrEP is recommended in men who have sex with men (MSM) and transgender individuals but may be considered in heterosexual women and men who are inconsistent in their use of condoms and have multiple sexual partners where some of whom are likely to have HIV infection. On the other hand, in Sub-Saharan Africa main users of PrEP are young women. Scaling Up PrEP Access in certain urban areas (San Francisco, Seattle, London, Sydney) where epidemics were driven MSM has resulted in population level reductions in new HIV infections. Higher rates of STIs among PrEP users have been noticed but it is still unclear if this is driven by taking more risk being on PrEP or being tested more often. PrEP users, according to current guidelines, should be seen every 3 months for HIV testing, STI testing and prescribing PrEP regimen. With such close monitoring many asymptomatic or neglected STIs could be diagnosed and treated resulting in better STI control on a large scale in certain population. To achieve its full potential PrEP should be combined with other prevention methods and it should not be seen just as a HIV prevention tool but also as an excellent STI surveillance method.

Human monkeypox virus infection (MPXV) is an endemic zoonotic disease prevalent in regions of Africa, that has recently spread worldwide. Since the start of the outbreak in May 2022, confirmed cases of monkeypox (MPX) have been reported from 29 EU/EEA countries. Transmission of MPXV occurs through large droplets, close or direct contact with skin lesions and contaminated fomites. Current spread of MPXV in Europe has predominantly affected men who have sex with men (MSM) which suggests transmission through sexual activity. The first case of MPX in Croatia was diagnosed at the University Hospital for Infectious Diseases (UHID) at the end of June 2022. We present information on the risk factors, transmission, clinical presentation and outcomes of MPX in patients treated at UHID. We present a case series of patients with polymerase-chain-reaction confirmed MPX infection who presented at UHID in the period of June – July 2022. Information on the risk factors, transmission, clinical presentation and outcomes of MPXV infection were abstracted from the medical records. We report data from 10 patients with monkeypox. All patients were MSM with suspected transmission through sexual activity. Median age was 36 years (IQR 29 - 50). The most prevalent symptoms were the presence of vesicular-umbilicated, ulcerative and pseudo- pustular skin lesions (90 %), localized lymphadenopathy (90%) and fever (80 %). The location of the lesions was predominantly in the genital or perianal area. Concomitant sexually transmitted infection was reported in 3 patients. Symptoms of urethritis was reported in 4 patients and proctitis in 2 patients. Monkeypox virus DNA was detected in pharyngeal swab in 3 patients, urethral swab in 1 patient, rectal swab in 4 patients and skin lesions in 7 patients. All cases were mild, self-limited and did not require hospitalization. Monkeypox is an emerging infectious disease in Europe where community transmission is reported, mainly in MSM. By presenting this case series we aim to draw attention to this new public health problem and emphasize.

Background: Delstrigo (doravirine/lamivudine/tenofovir disoproxil) is a recommended first-line antiretroviral (ART) regimen in the EACS guidelines [1]. It became available in Croatia in August 2020. This retrospective cohort study evaluated persons living with HIV (PLWHIV), ART naïve or experienced, who initiated or switched to Delstrigo, in Croatia. Materials and methods: We collected information from the electronic database of the Croatian HIV Reference Center and identified 90 PLWHIV who started Delstrigo from August 2020 until December 2021. Excluded from the analysis were three PLWHIV who started Delstrigo as a part of non-standard regimens and three PLWHIV who started Delstrigo after a discontinuation a of previous ART regimen for >1 month. We analysed 84 PLWHIV, 59 who switched to Delstrigo, and 25 were ART naïve. The follow-up was minimum 5 months. The data are presented by frequencies and percentages or median with first and third quartiles (IQR). Results: All PLWHIV were males, 77 (91.7%) were MSM. The median age of those who switched to Delstrigo was 45.0 (IQR 38.7 to 52.5) years ; 10 (16.9%) had previously clinical AIDS ; median time from HIV diagnosis was 9.1 (IQR 5.2 to 14.2) years ; median time on ART was 8.6 (IQR 5.1 to 12.5) years. PLWHIV switched from various ART regimens (Table 1). Before switch 57 PLWHIV had an undetectable viral load and two had low-level viraemia. During follow-up only one PLWHIV had low-level viraemia (

Background: In Croatia, persons living with HIV (PLWH) are treated and supplied with antiretroviral therapy (ART) only at the University Hospital for Infectious Diseases, Zagreb. Since about 55% of PLWH are not from Zagreb, we introduced ART on the first day of entry into care. We examined the frequency, virologic outcome, and factors related to same-day ART initiation from 2015-2020. Methods: Included were Croatian citizens/permanent residents ≥16 years old. Same-day ART was defined as ART initiation at the date of entry into care or the next day (Days 0 & 1). Multivariable logistic regression was done to assess factors related to same-day ART. We measured time from ART initiation to HIV-1 RNA < 50 copies/ml by Kaplan- Meier estimates. Results: Of 540 persons who entered HIV care, 530 started ART. Same-day ART was present in 348/530 (65.7%)(Table). Median time to ART initiation from HIV diagnosis was 8.0 days, rapid ART (within 7-days of HIV diagnosis) was initiated in 264/530 (48.9%). Of 348 same-day ART starters, 211 (60.6%) initiated ART within 7-days of HIV diagnosis. Same-day and rapid ART initiation was more frequent in 2018-2020 vs. 2015-2017 and increased from 2015 to 2020. Persons with no clinical AIDS were more likely to start same-day ART vs. those with clinical AIDS as were those living outside Zagreb. Same-day ART resulted in earlier viral suppression. Conclusions: Same-day ART became more frequent in recent years, it was associated with not having clinical AIDS and living outside Zagreb, and had a favorable virologic outcome.

BACKGROUND: Syphilis and other sexually transmitted diseases have increased in the last decade, especially among men who have sex with a man. In HIV- coinfected patients, syphilis may take a more aggressive course with neurological involvement. CASE PRESENTATION: A 28-year-old HIV- positive patient was referred to our HIV clinic for suspected meningitis. Two weeks before admission, the patient complained of progressive headache, without photophobia and phonophobia. He had fever up to 38˚C and complained of fatigue, general weakness, and loss of appetite. No visual or auditory disturbances were noted, and the neurologic exam showed no abnormalities. A head computed tomography scan was normal. Laboratory tests revealed a sodium serum level of 125 mmol/L, C- reactive protein 68.3 mg/L, thyroid-stimulating hormone 0.285 miU/L, adrenocorticotropic hormone 0.66 pmol/L, luteinizing hormone 1.6 IU/L. Cerebrospinal fluid (CSF) examination revealed mononuclear pleocytosis (35 cells/mm3) with a protein level of 1.56 g/L. Brain magnetic resonance imaging (MRI) revealed demyelinating subcortical lesions and a hypertrophic pituitary gland, which was suspected of a pituitary adenoma. Syphilis serology was performed, Treponema pallidum hemagglutination (TPHA) titers in serum were > 39 960, and the Rapid Plasma Reagin (RPR) was 64. The CSF TPHA was reactive 320, RPR was negative. He was treated with levothyroxine, hydrocortisone substitution, and empiric antibiotic treatment with ceftriaxone, ampicillin, and acyclovir, followed by crystalline penicillin for 10 days. All symptoms resolved after treatment. Syphilis serology on follow-up showed a good response to treatment, (RPR 16). A follow-up MRI of the sella turcica performed 3 months later was normal. CONCLUSION: We report a rare case of an HIV- positive patient with acute hypophysitis and hypopituitarism due to Treponema pallidum infection. Antimicrobial treatment, levothyroxine, and hydrocortisone replacement therapy resulted in resolution of all symptoms. Patients presenting with symptoms of hypopituitarism should be suspected to have hypophysitis caused by Treponema pallidum.

Background: People living with HIV (PLWHIV) are at increased risk for severe COVID-19 [1]. We aimed to evaluate the serological response after two doses of AZD1222 (ChAdOx1) SARS-CoV-2 vaccination in PLWHIV. Materials and methods: Participants were evaluated before the first dose (baseline) and 3 months after the second dose of the ChAdOx1 vaccine. Patient's sera were analysed using the SARS-CoV-2 IgG II Quant Architect Abbott assay [2]. An antibody concentration ≥50 arbitrary units per milliliter (AU/mL) was defined as positive (seroconversion) [2]. We also compared the immunogenicity of AZD1222 in PLWHIV to sex-matched healthcare workers (controls) who received two doses of the BNT162b2 vaccine. The study measurements were done from April to December 2021. Results: Fifty-nine PLWHIV were included: 57 men, median age 45.0 years, all receiving antiretroviral treatment and with controlled viral loads (58 with HIV RNA 200 CD4+ cells/μL, and the median CD4 cell count was 722 (IQR 520 to 878) cells/μL (Table 1). Eight (13.6%) PLWHIV were obese (≥30.0 kg/m2), and 31 (52.5%) were overweight (excluding obese). At baseline 56 PLWHIV had an antibody concentration

Background Croatia has a centralized care for people living with HIV (PLWHIV) and all patients are treated at the University Hospital for Infectious Diseases in Zagreb. Precautionary measures to control the spread of SARS-CoV-2 infection through quarantine and social distancing might have an impact on sexually transmitted diseases. The aim of this study was to report cases of syphilis in HIV+ men who have sex with men (MSM) and to describe whether there was a change during COVID-19 pandemic in year 2020 in comparison to years 2018 and 2019. Methods We reviewed all newly diagnosed syphilis cases among HIV infected MSM in Croatia during the year 2020 which included recent lockdown periods and compared them with previous years 2018 and 2019. The database of the Croatian HIV cohort was examined and we extracted clinical and treatment data for the syphilis cases. All cases with a diagnosis of syphilis were identified and reviewed for the clinical features and type of treatment. We describe our data with frequencies, median and first and third quartiles. Results A total of 140 patients had 171 episodes of syphilis. There were 33 patients with 35 episodes of syphilis in 2018, 45 patients with 47 episodes in 2019 and 82 patients with 89 episodes in 2020.Thus, we observed an 82% increase in the number of patients with syphilis and an 89% increase in episodes of syphilis between 2019 and 2020. The viral load was < 50 copies/ml in 94%, 93% and 95% of patients in years 2018, 2019 and 2020 respectively. There were no significant differences in the clinical presentation and treatment of syphilis in the period 2018 to 2020. Conclusions Measures undertaken to curb the COVID- 19 epidemic in Croatia, such as travel and movement restrictions, had no impact on the growing syphilis epidemic among HIV-infected MSM in Croatia. We observed a large increase in number of patients and episodes of syphilis during 2020 compared to 2019.

Objective: To describe the trend in prevalence of overweight and obesity in HIV-positive persons in Croatia, from 2016 to 2020. Methods: Included into the analysis were adults (≥18 years) who had at least one measurement of weight and height in the period 2016 to 2020. Body mass index (BMI) categories were: underweight (

A 56-year-old HIV positive patient was admitted to our hospital because of weight loss, prolonged productive cough with nodular pulmonary infiltrates on his chest X-ray and skin lesions. The patient was diagnosed with HIV in 2010. Antiretroviral therapy was initiated and patient was virally suppressed up until his last follow-up visit in 2016 when he decided to stop taking ART. In 2016 he developed severe psoriasis which was never confirmed via skin biopsy and was treated with topical therapy. Between June and October 2019. he received methotrexate with short-term success followed by worsening of symptoms. He also noticed a growing livid skin lesion on his nose. His clinical and family history were otherwise unremarkable. In his clinical status upon admission patient had diffuse red maculopapular skin lesions with squamous and hemorrhagic components on his chest, back and extremities. Also, there were two raised livid lesions on his nose and soft palate and small livid lesions on the back. His HIV status was evaluated and CD4+ lymphocyte count was 5/μl (0, 6%) indicating severe immunodeficiency, with viral load of 406 000 copies/ml. Serum serologic tests were negative for acute infection with T. pallidum, CMV, EBV, T. gondii and viral hepatitis. Quantiferon test was negative. Chest MSCT showed bilateral nodular lesions highly indicative of Kaposi sarcoma. There was no pathology found via bronchoscopy, however PCR for Pneumocystis jirovecii from bronchoalveolar lavage came back positive. Skin biopsy confirmed the diagnosis of psoriasis. Antiretroviral therapy was initiated (abacavir/3TC/dolutegravir) and pneumocystis was treated with trimethoprim/sulfamethoxazole. During hospitalization, patient received two courses of chemotherapy with liposomal doxorubicin and was discharged after 4 weeks. Between December 2019. and April 2020. he received in total 8 courses of chemotherapy after which he showed clinical improvement and regression of not only pulmonary lesions but also psoriasis and nodular skin lesions.

To describe the trend in prevalence prediabetes, type 2 diabetes mellitus (T2DM) and obesity among people living with HIV (PLHIV) in Croatia from 2016 to 2020 and evaluate factors related to prediabetes and T2DM. We included HIV-infected persons > 18 years old residing in Croatia and receiving care at the only HIV treatment centre in Croatia in the period 2016-2020. Prediabetes and T2DM were defined based on fasting plasma glucose, according to the American Diabetes Association (ADA, fasting plasma glucose 5.6 to 6.9 mmol/L and fasting plasma glucose ≥ 7.0 mmol/L respectively) and WHO definitions (prediabetes: fasting plasma glucose 6.1 to 6.9 mmol/L). Multinomial logistic regression of factors associated with prediabetes and diabetes was done. We analysed 1419 patients, females 139 (9.7%) and median age was 43.7 years. The overall prevalence of prediabetes was 47.4% (95% CI, 44.8-50.1% ) (ADA definition), 21.6% (95% CI, 19.5-23.9%) (WHO definition) and of T2DM it was 6.9% (95% CI, 5.6- 8.4%). There was no change in the yearly point prevalence of prediabetes and T2DM in the period 2016-2020. There was an increase in the prevalence of obesity (9.9%, 94/951 in 2016 and 14.3%, 154/1077) and overweight (40.3%, 383/951 in 2016 and 43.3%, 466/1077) in the period 2016 to 2020 (P-value for trend 0.02). The number of persons ≥50 years old in care increased from 29.1% in 2016 to 34.3% in 2020. The major factor related to the prevalence of T2DM and prediabetes were age and duration of HIV-infection. Other factors related to the prevalence of T2DM were hypertension, higher body mass index and serum triglycerides. We found a high prevalence of prediabetes in the HIV population in Croatia. As the population of HIV infected persons is aging early lifestyle interventions to reduce the risk of TD2M are needed.

Background: Cardiovascular disease is an important cause of morbidity among an ageing HIV population [1]. Despite the current evidence and known risk factors it is still challenging to determine to what extent HIV infection increases risk of peripheral artery disease (PAD)in comparison to general population. Here we examined the associa- tion between HIV infection, PAD and chronic kidney disease (CKD) in predominantly male HIV-infected persons compared with uninfected population. We also analysed risk factors related to PAD. Materials and methods: The cohort was comprised of 191 persons≥18 years old: 50 HIV-infected patients from the University Hospital for Infectious Diseases (UHID) in Zagreb and 141 non-HIV-infected patients from the Nephrology and Dialysis Department, Riuniti Hospital, Italy. HIV care in Croatia is centralised and all people living with HIV are treated at the UHID. Included were HIV- infected patients from 1 February 2018 to 30 September 2019, and non-HIV-infected patients from 4 September 2007 to 18 March 2019. CKD was defined as an eGFR of less than 60 mL/min/1.73 m2on at least two occasions 90 days apart. PAD was assessed using duplex color Doppler and was defined as having any of focal or diffuse medial or intimal calcification in iliac, common femoral, superficial femoral or tibial artery, diagnosed by grey scale vascular ultrasound. PAD was also considered present if there were haemodynamically significant stenosis or occlusion. Results: Of 191 participants 57.6% (110/191) were male with median age of 51 (IQR: 42 to 57) years. Fifty were HIV-infected (25 hadCKD) and of 141 non-HIV-infected 68 had CKD. The prevalence ofPAD was 76% (19/25, HIV+ CKD- yes), 32% (8/25, HIV+ CKD-no), 22% (15/68, HIV- CKD-yes) and 14% (10/73, HIV- CKD-no). BothHIV infection and CKD were associated with PAD (Table 1). Multivari-able analysis showed a significant interaction of body mass index(BMI) and CKD indicating that patients with CKD had more frequently PAD than those without CKD up to a BMI of 30 kg/m2. Conclusions: HIV-infected persons have PAD more frequently than non-HIV-infected patients and CKD worsens the findings. HIV infection and CKD are independent risk factors for PAD.

Background: Croatia has a centralized system of HIV care and all patients are treated at the University Hospital for Infectious Diseases (UHID) in Zagreb. The aim of our study was to examine factors related to rapid ART initiation among persons who entered HIV care in Croatia from 2005 to 2014. Materials/methods: Included into the study were Croatian citizens/residents ≥18 years who entered HIV care and started ART at UHID. Excluded were pregnant women and those who were in care elsewhere before entering care at UHID. The follow-up ended on Dec/31/2017 (earlier if died, moved or lost to follow-up). The time from HIV diagnosis to ART initiation was categorized: up to 30 days (“rapid”), from 31 days to one year (“intermediate”), and more than one year (“delayed”). We conducted quantile regression analysis to study factors related to the time from confirmed HIV-diagnosis to ART initiation with gap in care (>1 year without follow-up) considered the major predictor variable. Results: 628 patients were included into the study with a total of 4333.0 (median per-person, 6.7 [Q1-Q3: 4.3-9.5]) years of follow-up. 91.9% (577/628) were men ; median age was 36.1 (Q1-Q3: 29.6-43.8) years. The median time from HIV- diagnosis to ART initiation was 31 days (Q1-Q3: 0.3-17.7 months). Rapid ART initiation was observed in 49.8% (313/628) patients, 21.7% (136/628) and 28.5% (179/628) had intermediate and delayed initiation, respectively. On regression analysis, calendar year of entry into care, and markers of more advanced HIV disease (higher viral load, lower CD4 cell count and clinical AIDS) were significantly associated with earlier ART initiation. A gap in care before ART initiation was significantly associated with later ART initiation at all quantiles. Gap after ART, gender, transmission risk (MSM vs not MSM), age and place of residence (Zagreb vs outside Zagreb) did not have a significant impact on time to ART initiation. Conclusions: A significant proportion of patients started ART early in Croatia in the period 2005– 2014. Early ART initiation was not associated with a subsequent gap in care whereas longer waiting for ART initiation was associated with a gap in care before ART initiation.

Background: Calculate the efficiency of the EmERGE Pathway of Care for medically stable people living with HIV managed at five European HIV clinics (Table 1). The Pathway allows for EmERGE participants to communicate virtually with their caregivers. Methods: EmERGE participants, followed up between 2016 and 2019, mainly used HIV outpatient services. Micro-costing studies were performed at each site. Unit and annual costs were calculated in national currencies and converted to US$ 2018 OECD purchasing parity prices (PPPs). Costs were linked to mean per patient year (MPPY) use of outpatient services. Data on use of services were collected retrospectively one year before and prospectively one year after the introduction of EmERGE. Annual costs of HIV outpatient services were combined with primary outcome measures (CD4 count, viral load) to assess efficiency. Out-of- pocket expenditure data were also collected. Results: Two thousand, two hundred and fifty-one participants recruited: 87% to 93% men, mean age at recruitment 41 to 47 years ; 70% to 84% had full-time employment, median 37.5 hours/week and monthly income $1580 ; 5% to 16% participants received social services support, median $318 to 1558/month. Median sick days three months before enrolment was zero days (IQR 0 to 1) ; 50% to 82% participants did not take days off to visit clinic and the return trip took a median 1.5 to 2.0 hours at a median cost $5 to 41. MPPY outpatient visits decreased in four sites from 9% to 31% and associated costs from 5% to 33% (Table 1) ; use and costs increased by 8% in one site. Cost of ARVs comprised 83% to 91% annual outpatient costs. Annual costs of use of HIV services was similar across four clinics, but one site, located in one of the least affluent countries, had higher ARV costs. Primary outcome measures of participants did not change substantially during the study. Conclusions: Implementation of the EmERGE Pathway was efficient in all sites. ARVs were the main cost drivers ; a country’s national socio-economic situation should be considered when setting ARV prices. Other structural changes also affect costs, as demonstrated in two clinics, where changes resulted in reductions and increases of annual costs respectively. Future efficiencies can be anticipated by the introduction of the Pathway for all people living with HIV or those with other chronic diseases as has been demonstrated during the Covid-19 pandemic.due to the interruption of the work of community-based and other voluntary counselling and testing centres in Croatia.

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are among the most common bacterial sexually transmitted infections and disproportionately affect men who have sex with men (MSM). Large proportion of chlamydia and gonorrhea infections in men are asymptomatic, and therefore often undiagnosed and untreated which increases chances for complications and risk of transmissions. The aim of this study was to determine prevalence of chlamydia and gonorrhea infection among community- venue attending MSM in Zagreb, Croatia, between November 2019 and February 2020. Testing sites for each participant were determined based on self- reported sexual risk behavior. Urine, rectal and/or pharyngeal sample were pooled and real time PCR detection of CT and/or NG DNA was performed using Xpert CT/NG assay on the Cepheid GeneXpert Instrument Systems. The median age of 89 participants was 32 (standard deviation 8.39, age range 19-53 years). Most of the respondents (59.55%) had at least some university education, were employed (71.91%) and lived in an urban area (87.64%). Infection with Chlamydia trachomatis and/or Neisseria gonorrhoeae was detected in 14 (15.73%) participants, with 3 cases of coinfection with both bacteria. A total of 11 participants (12.36%) tested positive for chlamydial infection and 6 participants (6.74%) for gonococcal infection. The prevalence of CT and NG in MSM in our study is expectedly higher compared with Croatian general population and consistent with studies conducted in similar settings. However, well- educated men were reached disproportionately and different recruitment approach may be needed in order to include a more diverse spectrum of MSM.

Background: The burden of HIV care is influenced by AIDS-related and non-AIDS-related comorbidities (NAIDSC). All PLWHIV in Croatia are treated at the University Hospital for Infectious Diseases (UHID) in Zagreb. The aim of our study was to provide national period prevalence data of major comorbidities in PLWHIV in Croatia in 2019. Materials and methods: Included were Croatian citizens/residents ≥18 years who were seen at UHID in 2019 who ever had at least two visits >6 months apart. The following comorbidities were analysed: AIDS-defining diseases, myocardial infarction (MI), stroke, invasive cardiovascular procedures (ICPs), cancer both AIDS- (ADC) and non-AIDS- defining (NADC), end-stage liver disease (ESLD), endstage renal disease (ESRD), bone fractures and diabetes mellitus. All major comorbidities were expressed as percentages of the total HIV population in care and those ≥50 years old. Results: Of 1168 PLWHIV included into the study, 90.2% (1053/ 1168) were male, median age was 44.6 (Q1 to Q3: 37.6 to 53.5) with age ≥50 years in 405 (34.7%), main mode of transmission was sex between men (858, 73.5%) and heterosexual contact (239, 20.5%). Median age of those ≥50 was 56.5 years. The overall duration of HIV-1 infection was 7.5 (for those ≥50 years: 13.2) years, exposure to antiretrovirals was 6.4 (for those ≥50 years: 11.2) years. Chronic hepatitis B had 32 (2.7%) persons ; hepatitis C antibodies were positive in 57 (4.9%) of whom 39 (68.4%) had an undetectable HCV viral load. Overall major NAIDSC (without skin cancer) were present in 175 (15.0%, 95% CI: 13.0 to 17.2 ; in those ≥50 years: N = 90, 22.2%) persons (Table 1). NAIDSC occurred after an HIV- diagnosis in 100 (8.6%) and 74 (18.3% of those ≥50 years old) ; the most frequent being diabetes followed by ICP, MI and NADC. Of NADC after an HIV-diagnosis Hodgkin’s lymphoma was most frequent (n = 5). Fractures were predominantly traumatic and there were four cases of ESRD and no cases of ESDL. Clinical AIDS and ADC after HIV diagnosis occurred in 90 and 18 persons, respectively. Conclusions: The overall prevalence of major clinical NAIDSC was 15.0% for the total HIV population and 22.2% for those ≥50 years old. The prevalence of individual major NAIDSC for the whole HIV population ranged from 0.0% to 3.8% with diabetes being the most frequent.

Background: Calculate the efficiency of the EmERGE Pathway of Care for medically stable people living with HIV managed at five European HIV clinics (Table 1). The Pathway allows for EmERGE participants to communicate virtually with their caregivers. Methods: EmERGE participants, followed up between 2016 and 2019, mainly used HIV outpatient services. Micro- costing studies were performed at each site. Unit and annual costs were calculated in national currencies and converted to US$ 2018 OECD purchasing parity prices (PPPs). Costs were linked to mean per patient year (MPPY) use of outpatient services. Data on use of services were collected retrospectively one year before and prospectively one year after the introduction of EmERGE. Annual costs of HIV outpatient services were combined with primary outcome measures (CD4 count, viral load) to assess efficiency. Out-of- pocket expenditure data were also collected. Results: Two thousand, two hundred and fifty-one participants recruited: 87% to 93% men, mean age at recruitment 41 to 47 years ; 70% to 84% had full-time employment, median 37.5 hours/week and monthly income $1580 ; 5% to 16% participants received social services support, median $318 to 1558/month. Median sick days three months before enrolment was zero days (IQR 0 to 1) ; 50% to 82% participants did not take days off to visit clinic and the return trip took a median 1.5 to 2.0 hours at a median cost $5 to 41. MPPY outpatient visits decreased in four sites from 9% to 31% and associated costs from 5% to 33% (Table 1) ; use and costs increased by 8% in one site. Cost of ARVs comprised 83% to 91% annual outpatient costs. Annual costs of use of HIV services was similar across four clinics, but one site, located in one of the least affluent countries, had higher ARV costs. Primary outcome measures of participants did not change substantially during the study. Conclusions: Implementation of the EmERGE Pathway was efficient in all sites. ARVs were the main cost drivers ; a country’s national socio- economic situation should be considered when setting ARV prices. Other structural changes also affect costs, as demonstrated in two clinics, where changes resulted in reductions and increases of annual costs respectively. Future efficiencies can be anticipated by the introduction of the Pathway for all people living with HIV or those with other chronic diseases as has been demonstrated during the Covid-19 pandemic.

Background: New digital approaches to clinical management of HIV have potential to manage capacity whilst maintaining excellent clinical outcomes. This study examined the feasibility and uptake of a digital care pathway for people living with medically stable HIV at five clinical sites in Europe. Materials and methods: The EmERGE platform (Figure 1) was codesigned, developed and integrated into the IT systems at the five sites. Participants were seen once a year by their clinician with interim results checked, encrypted and pushed through to an app on their mobile phone. A pre- post study design was used with clinical and questionnaire data collected including: viral load outcomes ; serious adverse events (SAEs) ; patient activation [PAM-13] ; adherence [M-MASRI] ; quality of life [EQ-5D-5L ; PROQOL-HIV] ; system usability score [SUS] and patient experience at baseline [M0], 12 [M12] and 24 months [M24]. Changes over time were estimated using mixed effects regression models. Results: The GDPR- compliant EmERGE platform was successfully integrated at all sites during 2017. Two thousand, two hundred and fifty-one participants (mean 23.1% of clinic cohorts) were enrolled and followed up for between 12 and 30 months each. Demographics were representative of clinic cohorts: 91% male (2048/2251) ; 71% MSM (1598/2251) ; 27.9% aged over 50 (629/2251) ; 20.4% (460/2251) non-national at site. Virological outcomes remained excellent (10/2251 with confirmed VL > 50 ; none lost to clinical follow- up) ; no SAEs related to the pathway were reported. Patients were highly activated, no clinically important change was observed in PAM-13 score ; adjusted average continuous PAM-13 score at M12 compared to M0 -0.95 (99% CI -2.10, 0.19). Median self-reported adherence was 100% at each time point. Health-related quality of life was generally good although pain/discomfort and anxiety/depression were common (up to 34% and 44% respectively at M12) on EQ-5D-5L. Stigma was the lowest scoring domain of PROQOL-HIV. The usability of the platform was excellent [SUS score 85 at M12 and M24] ; 94.6% would recommend EmERGE to a friend. Conclusions: This co-designed digital health supported pathway offers a secure, safe, feasible and acceptable option for routine care to people living with medically stable HIV: providing individuals with access to their data and other information whilst helping clinics to manage capacity.

Infection with Human Immunodeficiency virus (HIV) is chronic, progressive disease which starts when HIV enters the organism. If not treated this condition leads to collapse of immunologic system, opportunistic infections and death. Introduction of antiretroviral therapy (ART) dramatically changed the prognosis of these patients. Modifications to ART regimens can occur for a number of reasons, including adverse effects. We have investigated the reasons and the frequency of ART modifications during the first 3 years after initiation of ART among 732 adult patients who started treatment in the period 1998-2013 in Croatia. We divided the patients in two groups: those who started ART between 1998 and 2005 and those who started ART between 2006 and 2013 and we found significant differences between periods. In the first period the most frequent reason for modification of ART were adverse effects and in the second one it was the decision of the physician guided by the prevention of adverse effects. Older age, female sex and certain drugs (stavudine) and drug classes (protease inhibitors) were significantly associated with the modification of the therapy due to adverse effects. Our findings were similar to many studies who analysed the same period. Less toxic and better-tolerated treatments should be available and used in Croatia in order to optimize the therapy.

Svrha: Izračunati isplativost oblika skrbi koji uključuje mHealth sustav, za klinički stabilne osobe koje žive s HIV-om, a koje su bolesnici Klinike za infektivne bolesti „Dr. Fran Mihaljević“, Zagreb, Hrvatska. Ovo omogućuje pojedincima da primaju informacije o liječenju HIV-a na svoj pametni telefon putem mHealth aplikacije. Metode: 293 sudionika studije EmERGE uglavnom su koristili usluge Ambulante za HIV, što je bio fokus troškovne studije. Jedinstveni troškovi izračunati su i povezani s prosjekom korištenja HIV usluga po godini bolesnika (MPPY). Podaci o korištenju usluga prikupljani su retrospektivno godinu dana prije i prospektivno godinu dana nakon uvođenja mHealth aplikacije, što je omogućilo procjenu godišnjih troškova pružanja HIV usluga. Godišnji troškovi kombinirani su s podacima o biomedicinskim i socijalnim ishodima – broju CD4 limfocita, viremiji, kvaliteti života (PROQOL-HIV) i samoupravljanju (PAM13), prije i nakon uvođenja aplikacije. Troškovi su izračunati u kunama. Rezultati: Prosječni ambulantni posjeti smanjeni su sa 5, 2 (95% CI: 4, 9 do 5, 5) na 4, 75 (95% CI: 4, 5 do 5, 0) MPPY. Godišnji troškovi bili su prije mHealth 43.313kn (95% CI 42.933 – 43.708kn) i 42.063kn (95% CI 41.747 – 42.397kn) ; ART je činila 82-84% godišnjih troškova, testovi 10%. Nisu primijećene značajne razlike u broju CD4 limfocita, a prosječna viremija je ostala nemjerljiva između razdoblja. PROQOL-HIV i PAM13 rezultati ostali su visoki i nisu se statistički razlikovali tijekom 12 mjeseci korištenja aplikacije. Zaključak: Godišnji troškovi prije i nakon uvođenja mHealth sustava smanjeni su za 1%, učinkovita intervencija ; ART je glavni izvor troškova. Sudionici su nakon uvođenja mHealth sustava u skrb ostali klinički stabilni, kao i njihova kvaliteta života i sposobnost samoupravljanja. Može se očekivati i buduća učinkovitost uvođenjem mHealth sustava kroz Kliniku. Dodatne analize uključivat će troškove za bolesnike.

Purpose: To assess the potential effectiveness of a co-designed reduced visit pathway of care for individuals living with stable HIV in terms of empowerment (which encapsulates patient confidence, skills and knowledge to self-manage health and care). Methods: People living with stable HIV across five diverse clinical sites in Europe were invited to take part in the EmERGE study - whereby individuals are seen once, instead of twice, a year by their clinician - with their interim visit supported via an mHealth platform. We report here on preliminary data on the primary outcome, empowerment, measured by PAM-13 (Patient Activation Measure-13) at baseline (M0) and 12 months (M12). Results: PAM-13 was available on 2112/2251 (93.8%) of participants at M0 and 1026/1439 (72.3%) at M12. The overall proportion of participants at low activation Levels (L) 1&2 was 12.4% (261/2112) at baseline, ranging from 10.5% in Antwerp to 13.5% in Zagreb. At M12, the overall proportion was 14.1% (145/1026), ranging from 9.0% in Zagreb to 17.1% in Barcelona. Change in activation from L1&2 at baseline to L3&4 at M12 was achieved by 63/101 (62.4%) L1&2 baseline participants whilst 93/891 (10.4%) of baseline participants at L3&4 had dropped to L1&2 by M12 ; 836/992 (84.3%) did not switch between L1&2 and L3&4. The distribution of participants across each of the four levels of PAM-13 was similar across sites at baseline with≥86% of participants with the highest levels of activation. At four out of five sites, the proportion at L3&4 is currently lower at M12 than at M0. Conclusions: The majority of participants had a high level of empowerment at baseline. Over 60% of respondents in the lowest categories of PAM-13 (L1&2) at baseline shifted to L3&4 in M12. The proportion of participants at low activation levels was similar between sites. Follow-up continues until October 2019.

Background: All HIV-infected persons in Croatia (population: 4.2 million) are treated at one center, the University Hospital of Infectious Diseases (UHID), Zagreb. The aim of this study was to assess the population trend in presentation to care with AIDS-defining conditions (ADC) and to describe whether there was a change in the type of the presenting ADC in the period 2001-2017. Materials/methods: The data were extracted form the electronic databaseat UHID. Included into the study were Croatian citizens or permanent residents whose first ever presentation to HIV care was with an ADC. The population trend over time was analyzed by annual percent change (APC) using the Joinpoint program. ADC were compared over 3 periods (2001-2006, 2007-2012, 2013-2017) with thechi-squaretest for trend. Results: Of 1174 persons who never received HIV care before elsewhere, 240 (20.4%, median age:42.6 years) presented with and ADC. The rate of ADC per one million inhabitants was low (1.6 to 4.7) ; it increased (APC=2.8%, p=0.058) over time, particularly in males (n=215, APC=3.4%, p=0.017), but remained very low and unchanged in females (n=25, p=0.331) (Figure). The proportion of persons with ADC among all first-time receivers of HIV care declined from 18.0% in 2001 to 12.1% in 2017 (p=0.011).There was an increasein the proportion of males (period 2001-06: 58/70, period 2013-17: 75/84 ; p-trend=0.039) and MSM (period 2001-06: 28/70, period 2013-17: 69/84 ; p- trend

Ciljevi: prikazati radiološko-kliničku korelaciju spektra najčešćih bolesti središnjeg živčanog sustava (SŽS) u bolesnika zaraženih HIV-om u Hrvatskoj, liječenih u Klinici za infektivne bolesti u Zagrebu, u posljednjih pet godina (od 1. siječnja 2014. do 31. prosinca 2018.): HIV- encefalopatija, progresivna multifokalna encefalopatija, primarni limfom, metastatski limfom i toksoplazmoza. Metode: retrospektivno prikupljanje i radiološka analiza slikovnog materijala izabranih bolesnika (kompjutorizirana tomografija-CT, magnetna rezonancija-MR), arhiviranih u digitalnoj arhivi Klinike. Retrospektivno prikupljanje epidemioloških, kliničkih i laboratorijskih podataka iz bolničkih kartona koje su obavljali infektolozi. Formiranje serije prikaza s radiološko-kliničkom korelacijom uz izdvojene, klinički relevantne podatke važne za dijagnostiku, liječenje i prognozu bolesnika. Rezultati: diskusija o najvažnijim slikovnim karakteristikama i diferencijalnoj dijagnostici različitih bolesti SŽS-a u bolesnika zaraženih HIV-om. Prikaz i obrazloženje ograničenja pojedinih slikovnih tehnika koje mogu uzrokovati odgađanje u postavljanju ispravne dijagnoze. Navođenje važnih točaka koje radiolog mora prezentirati infektologu i neurokirurgu. Zaključak: bez obzira na uspješnu antiretrovirusnu terapiju, bolesnici zaraženi HIV-om su u riziku za razvoj različitih oportunističkih bolesti SŽS-a. Brza slikovna dijagnostika može ograničiti oštećenja SŽS-a.

Purpose: Estimate the cost-effectiveness of introducing a mHealth supported Pathway of Care for clinically stable people living with HIV in Zagreb. The EmERGE Pathway enables individuals to receive HIV treatment information on their smart-phone via the mHealth App. Method: 293 study participants predominantly used HIV outpatient services, the focus of the costing study. Unit costs were linked to mean per patient year (MPY) use of HIV services. Data on use of services were collected retrospectively one-year before and prospectively one-year after the introduction of the mHealth Pathway, enabling annual cost of HIV service provision to be estimated. Annual costs were combined with outcome data, changes in CD4 count and Viral Load one-year before and after the introduction of the mHealth Pathway. Costing were calculated in Croatian Kuna and converted to Euros. Results: Mean outpatient visits decreased from 5.2 (95% CI: 4.9 to 5.5) to 4.75 (95% CI: 4.5 to 5.0) MPY. The annual costs of service provision were €8, 885.30 (95% CI €8, 833.90 to €8, 938.60) pre-mHealth and €8, 716.20 (95% CI €8, 673.40 to €8, 761.40) post-mHealth ; clinic visits and tests comprised 10% of total costs, ARVs 55% and other pharmacy costs 35% of annual costs. No significant differences in CD4 counts were observed between periods and Viral Load remained undetectable during each period with no significant difference between pre-mHealth and post-mHealth values. Conclusion: Annual cost pre- and post- mHealth Pathway decreased by 2%. Cost for ARVs and Pharmacy services were the greatest cost drivers. Participants remained clinically stable after the introduction of mHealth Pathway of Care, which has been an efficient intervention. Future efficiencies can be anticipated with introduction of the Pathway across the clinical site. Additional analyses will include other outcomes such as quality of life (PROQOL-HIV), self-management (PAM13) and patient out-of-pocket expenditures.

Purpose: We describe where the HIV diagnosis was made, linkage to care and the time from HIV diagnosis to antiretroviral therapy (ART) initiation in Croatia, 2013 to 2018. Methods: Croatia has a centralized system of care and all HIV patients are treated at the University Hospital for Infectious Diseases (UHID) in Zagreb. Data on persons entering care were extracted from the electronic database at UHID. Included were the persons that were nationals or residents of Croatia that have previously not been in care elsewhere. Results: Overall 587 patients entered care from 2013 to 2018. The first HIVpositive test was done at: hospitals (other than UHID) in 150 (25.6%) persons, voluntary counselling and testing settings in 147 (25.0%), UHID in 103 (17.5%), community-based settings in 85 (14.5%), other places in 62 (10.6%) and unknown sites in 40 (6.8%) persons. For the period 2014–2018, linkage to care among those who entered care, was within 7 days of the first HIVpositive test in 53%, within 14 days in 78% and within one month in 91% persons. The median CD4+ cell count at entry into care ranged from 255/lL in 2017 to 341/lL in 2018. It was very low when HIV was diagnosed in hospital settings (median, 84/lL) and highest when HIV was diagnosed at community-based settings (median, 413/lL). In 2017 and 2018 ART was initiated within 24 hours from the first clinical visit in 78% and 71% persons respectively, whereas in 2014–2016 it was initiated in 36–62% persons. Conclusion: Community-based HIV testing contributed to earlier HIV diagnosis. Linkage to care was very good and rapid ART initiation is currently a common practice in Croatia. Expanding community-based HIVtesting accompanied by prompt linkage and early ART might contribute to the decrease of new HIV-infections in Croatia.

In the era of well-treated HIV, attention is turning towards how successful ageing can be achieved for all. Integral to this success is personal well-being which can be influenced by perceptions of ones’ ageing. Purpose: To describe perceptions of ageing among individuals living with stable HIV engaged with remote healthcare delivered via a novel smartphone application (‘app’). Method: All EmERGE participants were eligible for this ageing sub-study. Two questions drawn from the US Health and Retirement Study assessed: 1) satisfaction with ageing, rated on a Likert scale (strongly disagree to strongly agree), 2) ‘What age do you feel?’. Lastly, participant opinion on inclusion of information on ageing issues within the ‘app’ was sought. Results: 944 individuals participated across five European study sites. Mean age was 44.6 (SD=9.9), with 32.6% aged>50. 91.5% were male and 79.4% were Caucasian. 99% responded to the statement ‘So far I am satisfied with the way that I am ageing?’ with the majority either somewhat or strongly in agreement (68.8%) and 14.7% either somewhat or strongly disagreed, as shown in table 1. Satisfaction did not vary by age, except for greater dissatisfaction in over 60s. The overall mean age felt (n=916) was 39.4 (SD=10.8), with mean difference from actual age of 5.2 years. 10.4% felt their age, with most (69.5%) feeling younger (by a median of 7 years, IQR 4–11) and 20.2% feeling older (by 3 years, IQR 1–7). The proportion feeling younger increased with increasing age group (p

Preekspozicijska profilaksa HIV infekcije

Background: In Croatia, HIV-careincluding antiretroviral therapy (ART) is provided ata single institution, the University Hospital of Infectious Diseases (UHID) in Zagreb. We describe whether and when an apparent change in the trend in the prevalence of ART prescriptions occurred from January 2005 to December 2017. Materials/methods: Included were all patients who have been given ART from the hospital pharmacy at UHID. ART was categorized: 1) 2NRTI+1NNRTI, 2) 2NRTI+1PI, 3) 2NRTI+1INSTIand 4) other combinations. The nucleoside backbone was categorized: 1) D4T+3TC, 2) ZDV+3TC, 3) TDF+FTC, 4) ABC+3TC and 5) other combinations including nucleoside-sparing regiments. For each calendar year the total number of person-years on ART was calculated and the percent of time spent on a particular drug combination was calculated. Trends are described by Annual Percent Change (APC) using the Joinpoint Regression Program. Results: A total of 1296 (88.9% males) persons received ART at UHID in the period 2005-2017 with a total of 7216.8 person-years of follow-up. There were 226.0 person-years of therapy in 2005 and 1032.2 in 2017 (average annual increase=13.5%). The prevalence of standard 3-drug therapy (2NRTI plus one other agent of the NNRTI, PI or INSTI class) was >90% in each year except in 2017 when it was 88%. There have been significant changes in ART prescriptions particularly after 2015 with an increasing use of integrase inhibitors and non- standard ART (Figure).The use of NNRTI has decreased since 2015 where as the use of PI had a decreasing trend since 2010 (Figure). Some of the ART prescriptions were influenced by costand availability (TDF/FTC and ABC/3TC). There were 36 different combinations used by 265 patients in 2007 and 51 used by 1116 patients in 2017. Among non standard combinations, use of lopinavir-mono therapy was most prevalent before 2015 (14.6% of person-years of non-standard ART usage), afterwards it was dolutegravir plus lamivudine (36.9%). Conclusions: Our complete national data indicate significant changes in antiretroviral drug usage over time, particularly after 2015. Changes in ART were not abrupt. Among non-standard regiments non- NRTI or single-NRTI (3TC) ones were most prevalent indicating that they were prescribed mostly because of tolerability and side-effects.

OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) caused by the reactivation of JC virus is a progressive demyelinating central nervous system disease occurring in immunocompromised patients, such as patients with HIV infection with CD4+ T lymphocyte count bellow 200/mm3. Our goal was to give an overview of HIV patients with PML treated at our clinic in the period from 2011 to 2019. METHODS:The database of the Croatian HIV cohort was examined and all patients with positive JC virus from cerebrospinal fluid from January 2011 to March 2019 were extracted. We present their laboratory, epidemiological and clinical data. RESULTS: In the examined period a total of 6 patients with HIV infection were diagnosed with PML by detection of JCV DNA in cerebrospinal fluid. All treated patients were males aged between 28 and 49 belonging to MSM (men who have sex with men) risk group. All patients had CD4+ lymphocyte count bellow 100/mm3 at the time of presentation and in all PML was the first AIDS indicator disease. One patient developed PML due to discontinuation of antiretroviral therapy (ART) several years after the diagnosis and another had PML-IRIS after the introduction of ART. Three of six patients died with a median survival rate of 175 days (range 24-256 days), and all three surviving patients had neurologic sequele. CONCLUSION: Although relatively rare, PML must be considered in immunocompromised patients with neurological deficits. Since we had a small number of patients, no statistically significant conclusions could be made. However, it is clear that PML remains a debilitating and deadly disease for many patients with HIV despite antiretroviral therapy. Our data corresponds with the data from the literature stating one-year survival rate of 50% or more in patients on ART and 55 to 80% chance of severe neurologic sequelae in survivors.

Infekcije humanim papilloma virusom (HPV) su najčešće virusno spolno prenosive infekcije. Svake godine otprilike 17, 500 žena and 9, 300 muškaraca dobiju karcinom uzorkovan HPV-om. Otprilike 1 od 100 spolno aktivne osobe ima šiljaste kondilome. Osobe s HPV infekcijom sklonije su nastanku HIV infekcije - rizik za infekciju HIV-om u osoba s HPV infekcijom je udvostručena. HIV pozitivni bolesnici imaju povećanu prevalenciju i incidenciju HPV infekcije (posebice HPV povezanih displazija). Karcinomi povezani s HPV-om su najučestaliji karcinomi u bolesnika s HIV-om. Zbog visoke incidencije i perzistencije infekcije, HIV pozitivni bolesnici imaju povećani rizik za nastanka karcinoma povezanih s HPV-om. Incidencija analnog karcinoma, orofaringealnog karcinoma, karcinoma penisa, vulvovaginalnog karcinoma u HIV pozitivnih osoba je u povećanju neovisno o uvođenju HAART terapije. Incidencija cervikalnog karcinoma u HIV pozitivnih osoba je visoka, po uvođenju HAART-a ne raste, ali nema dokaza niti o smanjenoj učestalosti

Mobile technology platforms represent a method of streamlining long-term HIV care, yet they may fail to address broader health issues such as agerelated conditions. Purpose: To estimate the prevalence of frailty and falls among stable individuals with HIV engaged with remote healthcare, delivered via a novel smartphone application. Method: Cross-sectional, questionnaire-based sub-study of EmERGE participants. Frailty was assessed using the FRAIL scale, a five-item selfreport screening tool. Present criteria were summed (range 0–5) and catergorized: 0=robust, 1–2=pre-frail, ≥3 frail. Falls and their frequency were assessed and dichotomised to faller/non-faller and single/recurrent falls. Results: 944 individuals participated across five European study sites. Mean age was 44.6 years (SD 9.9), with 33% aged>50. 92% were male, 79% were of Caucasian ethnicity. Full frailty data were available for 891/944 (94%). Three quarters were robust (74%, 663/891) ; 25% (219/891) pre-frail ; and 9 frail (1%). Of the frailty criteria, fatigue was most frequently reported (13%) followed by unintentional weight loss (12%), problems with walking (6%) and stairs (5%). Only 2 participants reported>4 comorbidities. Demographic data were available for 6/9 frail individuals: 83.3% were aged>50 ; all were male. 120/940 (13%) participants had fallen in the last year. Fallers experienced a median of 2 falls (IQR 1–3), with 59% (68/116) falling recurrently (≥2falls). Fallers were on average 3.1 years older than non-fallers (95% CI 1.2–5.1), with a greater proportion aged>50 (44% vs 31%, p=0.005). Falls were more common in frail (5 vs 1%) and pre-frail individuals (43 vs 22%). Conclusion: Ageing issues were relatively uncommon in this cohort. Frailty was rare, with pre-frailty seen in 25%. Falls occurred and often recurred, and were related to frailty status and older age. Opportunities to explore ageing concerns with patients should be retained within mHealth delivered care and comprehensive geriatric assessment considered if identified.

Purpose: To assess the feasibility, usability & acceptability of a co-designed mHealth supported pathway of care for individuals living with stable HIV. Methods: Following a detailed background assessment, a co-design process was facilitated with community and clinicians at five diverse clinical sites across Europe, informing the development of the platform (Figure 1) within a reduced visit pathway of care. Individuals living with stable HIV (based on WHO criteria) are seen annually by their clinician with interim bloods drawn (6 & 18 months) ; results checked, encrypted and pushed securely to their mobile device alongside medication, appointment and other information. Data are reported on uptake, usability (System Usability Scale (SUS)) and experience over the first year. Results: The platform was successfully co-designed, developed and integrated into hospital ICT systems at the five sites ; GDPR compliance was ensured. 2251 participants enrolled in the study: uptake varied by site (10%-37% of respective cohorts). Reasons for non-participation included: clinician engagement (change to practice ; lack of virtual tariff ; perceptions of digitalising clinical work) ; patient choice (change to current pathway ; no smart phone ; confidentiality) ; technical aspects & research questionnaires also contributed. Of the 1439 individuals with 12 month data available to May 2019: 1222/1316(92.7%) were male ; median age 44 (range 20–75) ; 1077/1288(83.6%) MSM ; and 271/1318(20.6%) non-national at site. Viral load was undetectable at 12 months in 1229/1241(99%) ; no SAEs related to the pathway were reported. Usability rating was excellent: median SUS score 85/100 (IQR 70–95) & patient reported experience positive: 82.9% rated their experience as good/excellent ; 94.2% would recommend to a friend. Conclusions: The EmERGE pathway is a feasible and acceptable option in the menu of care for individuals living with stable HIV. Uptake has varied by site and learning gives insights into factors affecting roll out of such options. To date usability and reported experience is very good.reduced visit pathway of care.

Outbreak of acute hepatitis A among HIV-infected men who have sex with men, Croatia, 2017-18 Background Croatia, like other European countries has gradually shifted from a high endemicity level to a low endemicity level for hepatitis A virus (HAV) infection. In 2016/2017 sexually-transmitted hepatitis A outbreaks were described among men who have sex with men (MSM) in several European countries. We describe clinical features of hepatitis A in HIV-infected MSM from Croatia during the 2017/2018 outbreak. Methods The database of the Croatian HIV cohort was examined for the presence of hepatitis A IgG and IgM antibodies from January 2005 to March 2018. We extracted laboratory, epidemiological and clinical data for the cases and describe our data with frequencies, median and range. Results Of 1226 persons tested for HAV antibodies 419 (34.2%) were positive for anti-HAV. No cases of acute HAV were identified from 2005 to 2016. Eleven cases of acute HAV infection, all among MSM, were identified between March 2017 and March 2018. Nine patients were symptomatic with jaundice and nausea/vomiting and six had fever. The two asymptomatic patients were identified because routine testing for HAV antibodies for MSM with prior negative tests was introduced in September 2017. The median age was 44.5 (25.9-56.2) years and the median CD4+ cell count was 494 cells/µL. Antiretroviral therapy (ART) was stopped in seven patients due to fear of added hepatotoxicity. Three patients continued their regimen, two of which had mild or no elevated liver enzymes and one patient refused to stop ART. In one patient HIV and HAV infection was diagnosed concurrently, this patient started ART after recovery from acute hepatitis. All patients had a full recovery. Conclusions Our findings indicate that HIV infection did not affect the course of hepatitis A. There is a need for routine screening of HIV infected MSM to identify asymptomatic infections. Wider use of hepatitis A vaccination is warranted.

Osobe koje žive s HIV-om su općenito vrlo dobro praćene. Ako dolaze redovno na svoje kontrolne preglede do vremena kada se mogu smatrati "starijima", u skrbi za HIV oboljeli su godinama, a neki i desetljećima. Tijekom tog vremena su podvrgnuti nizu rutinskih testiranja, pretraga i pregleda. Osim toga HIV specijalisti prikupljaju informacije i o drugim bolestima i stanjima koja se javljaju tijekom godina praćenja. Ove informacije mogu biti od iznimne važnosti liječniku obiteljske medicine ili nekom drugom specijalistu u bliskoj budućnosti kada ovi, sada već stariji bolesnici, budu zahtijevali neku drugu medicinsku pomoć osim one koju im pruža njihov HIV specijalista. Svi ovi podaci obično su pohranjeni u HIV klinikama u papirnatoj ili elektronskoj formi, ali do njih nije uvijek lako doći. Ako se bolesnik, primjerice, zatekne u nekoj hitnoj službi druge bolnice ili pak u inozemstvu praktički je nemoguće doći do relevantnih informacija ako ih bolesnik nema sa sobom. S druge strane mnoge osobe koje žive s HIV-om (po našem iskustvu takvih je većina u Hrvatskoj) nisu skloni otkrivanju svojeg HIV statusa drugim medicinskim djelatnicima, ako to nije apsolutno neophodno. Za to postoji puno razloga, a najveći je još uvijek prisutna stigma HIV dijagnoze. Na par primjera ćemo pokazati kako naoko izvrsne ideje nisu bile djelotvorne u praksi i neke primjere novih tehnoloških rješenja za koje se nadamo da će biti korisna. Smatramo da nema jednog rješenja koje će odgovarati svima i zato je važno stalno tražiti nove i raznolike pristupe za populaciju osoba koje stare s HIV-om.

Introduction: In the last two decades life expectancy of person infected with HIV was prolonged, mainly due to usage of antiretroviral drugs, resulting in increased number of HIV + elderly (>50 years) people. Considering the complexity of health in elderly providing care for that population can be challenging. The aim of our study was to describe characteristics and trends in persons older than 50 years who entered HIV care for the first time in Zagreb, Croatia in period 2007 to 2017. Methods: This study included elderly (>50 years) persons who have never been in HIV care elsewhere in the period from January 2007 do December 2017. Descriptive statistics was used for categorical and continous variables. The Mann Whitney test was used to analyze late presentation to care, CD4+ cell count and viral load across different categories of age (18 to 29, 30 to 39, 40 to 49, and >50 years). Results were analyzed with SAS version 9.4, and Joinpoint software was used to assess the trend in the rate of males entering HIV care from 2007 to 2016. Results: Among 882 adults (>18 years) who entered HIV care from 2007 to 2017, 99 (11.2%) were older that 50 years (median: 54.9 years). Elderly patients were mstly male (91.9%), not residents of the Zagreb area (71.7%), and man who have sex with men (62.6%). When compared to the other age groups the median CD4+ T-cell count was the lowest (121 per mm3) and the viral load was highest (median 251 188 copies/mL) among elderly persons. The proportion of persons with cd4+ T-cell counts below 200/mm3 (62.6) and with viral load >100 000 HIV1 RNA/mL was highest (68.7%) in the age group of >50 years. The highest proportions of late and very late presenters were found in elderly (83.8%) and 62.6%, respectively). Rates per 100 000 inhabitants of HIV+ men and elderly HIV+ men who entered care increased significantly in the observed period (from 2.36 in 2007 to 4.65 in 2016 for all males p

Introduction: Gonorrhoea is one of the major causes of morbidity among sexually active individuals worldwide. Neisseria gonorrhoeae (NG) usually causes urethritis in men and cervicitis in women. However in certain groups, such as men who have sex with men (MSM) extra genital infections (pharynx and rectum) are common. Nucleic acid amplification testing (NAAT) is the preferred test but the culture still remains important because of ability to determine susceptibility of the isolate. Resistance to various antimicrobial agents that were effective earlier has been reported worldwide. Goal: Our goal was to present the data on the diagnosis and treatment of NG in STI service concentrated to high risk MSM population. Methods: This retrospective observation included men that had NG positive NAAT and were diagnosed and treated in STI Clinic and Emergency Department at the University Hospital for Infectious Diseases from October 2014 to July 2017. Results: From October 2014 to July 2017 in STD Clinic around 550 men were examined and screened for various sexually transmitted infections. Out of them 73 (mostly MSM) had laboratory confirmed gonococcal infection from rectum, pharynx and/or urine/urethral swab using NAAT. Five of them were HIV positive and 11 had co-infection with Chlamydia trachomatis. Our microbiological laboratory isolated 23 NGs, all from urethra. All patients were successfully treated with dual antimicrobial therapy (cefixime or ceftriaxone + azithromycin). No resistance to ceftriaxone and azithromycin were detected. All tests of cure (TOC) that were done came out negative for NG. Conclusion: Dual antimicrobial therapy is highly effective. We have found no resistance to ceftriaxone or azithromycin in our patients. Although NAAT is the most accurate and preferred diagnostic test, isolation of bacteria is still needed for local surveillance of antimicrobial resistance

A wide range of infectious, neoplastic, and inflammatory dermatoses can affect the anogenital region and manifest with ulcerations. The most frequent causes of painful genital ulcers are herpes simplex infection, syphilis and Haemophilus ducreyi infection (chancroid). Granuloma inguinale and lymphogranuloma venereum are rare causes of genital ulcerations. However , various other infectious and noninfectious dermatoses should also be considered as a possible cause of ulcerations in anogenital region. We present a case of a 22- year-old patient who, during a physical examination, had an ulceration of 1cm in diameter surrounded by a few smaller ulcerations in the perianal region. All the ulcerations were painful on palpation, with a yellowish discharge appearing on pressure. There was no regional lymphadenopathy and the patient denied having any prodromal symptoms. The patient history revealed occasional sexual intercourse with male partners. The first suspected diagnosis was syphilis with the coexistence of herpes genitalis, but due to the clinical picture and patient history, lymphogranuloma venereum was also suspected. Serology for syphilis, HIV and hepatitis was negative. Urethral swabs for Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalis were negative, except for Ureaplasma urealyticum which was unremarkably positive 103. Perianal and rectal swabs for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma hominis, Mycoplasma genitalis and Ureaplasma urealyticum were positive for Neisseria gonorrhoeae. Polymerase chain reaction (PCR) analysis for HSV 1 and HSV2 of perianal ulcerations was positive (HSV IgM: positive). The patient was treated with acyclovir 3x400 mg for 7 days, doxycycline 2x100 mg for 3 weeks and ceftriaxone 1gr intramuscular injection, which led to complete resolution of clinical symptoms. We believe that our patient had perianal ulcerations of multiple etiologies combined, such as herpes simplex infection, gonorrhea and/or lymphogranuloma venereum. All the patients with genital ulcers thought to be caused by an STI should be tested for syphilis, HIV, and herpes simplex, and also to other STI causative agents like Neisseria gonorrhoeae and Chlamydia trachomatis (serovars L1, L2, and L3), depending on patient’s history.