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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.

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: HIV/AIDS remains a challenge for intensive care physicians, despite the availability of antiretroviral therapy (ART). Outcomes of patients with HIV treated in the ICU are underinvestigated. Methods: We retrospectively reviewed adult HIV/AIDS patients treated in the ICU, University Hospital for Infectious Diseases, Zagreb, Croatia, from 1996 to 2020. Follow-up was in December 2021. Short-term outcomes included: vital status, length of stay (LOS), and modified Rankin Scale (mRS) at discharge. Long-term outcomes were: vital status, mRS, and ART adherence at follow-up. The favorable functional status was mRS 0-2. Results: Out of 8484 ICU patients, 98 (1.2%) had HIV/AIDS (48.5±11.3 years-old, 83, 90.2% male) For 53 (57.6%), this was inaugural admission, while 39 (44.4%) had previous HIV/AIDS diagnosis (25, 64.1%, adherent to ART). The most common condition (35, 66.0%) in newly diagnosed HIV/AIDS patients was Pneumocystis jirovecii pneumonia, while non- AIDS related events were the most frequent (25, 64.1%) in previously diagnosed patients adherent to ART. Mechanical ventilation was used in 64 (69.6%), VV-ECMO in 8 (8.7%), and continuous renal replacement therapy in 22 (23.9%) patients. ART was administered to 60 (65.2%) patients ; ten (10.9%) had immune reconstitution inflammatory syndrome. There were 48 (52.2%) in-hospital deaths, 44 of which were in the ICU. The median ICU and hospital LOS were 8 (1–143) and 33 (3–232) days, respectively. At discharge, 14 (15.2%) patients had moderate to severe disability (mRS 3- 5), while 30 (32.6%) had favourable functional status. Forty survivors (90.9%) were available for follow-up after a median of 64 (1-230) months. Nine patients (22.5%) were deceased, 7 (17.5%) had moderate to severe disability (mRS 3-5), 28 (70.0%) patients had favourable functional status. All patients available for follow-up were adherent to ART. Conclusion: More than half of critically ill HIV/AIDS patients were newly diagnosed and treated for opportunistic infections. Short-term outcomes were unfavorable, with high mortality and frequent disability. Long-term outcomes for survivors included low mortality and a high favorable functional status rate. All survivors were adherent to ART at follow-up.

Background: Nocardia spp. are opportunistic pathogens most commonly affecting immunocompromised patients. We describe a case of disseminated nocardiosis in a patient newly diagnosed with HIV. Case report: A 45-year-old male presented with a three-week history of swelling and pain in the right knee. Purulent arthritis was diagnosed and treatment with intravenous antibiotics, arthroscopy, joint lavage and arthrotomy was undertaken. Nocardia sp. was isolated from intraoperative samples. The patient also had a history of frequent Candida balanitis and recent weight loss, so he was tested for HIV and the test came back positive. His CD4+ count at the time of HIV-diagnosis was 24 cells/uL, with a viral load of 148 353 HIV-1 RNA copies/mL of plasma. Pulmonary involvement was confirmed by a chest CT scan, multiple abscesses in lower extremities were diagnosed by ultrasonography, lower extremities CT scan, and whole-body PET-CT scan. Signs of femorotibial osteomyelitis of the right leg were also found. His brain CT scan was normal, and he didn't develop any neurologic symptoms during follow-up. He was treated with a combination of imipenem and co-trimoxazole intravenously (for a total of 73 days), which was continued with an oral regimen of co-trimoxazole and ciprofloxacin. Antiretroviral therapy (ART) with bictegravir/emtricitabine/tenofovir alafenamide was initiated, and on the 70th day of therapy his viral load became undetectable, the CD4+ count remained low (30 cells/uL). Multiple leg abscesses showed almost complete resolution, a follow-up chest CT scan showed residual small bilateral nodular infiltrates, and his general condition improved markedly. Conclusions: In patients with severely impaired cellular immunity, we can expect rare pathogens presenting with unusual clinical syndromes. Prompt diagnosis and adequate treatment of both the opportunistic disease and HIV infection is important to achieve a favorable outcome

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: Croatia has a low-level HIV epidemic, men who have sex with men (MSM) are mainly affected [1]. HIV care is centralised, all people living with HIV (PLWHIV) are treated at the University Hospital for Infectious Diseases (UHID) in Zagreb [2]. We assessed temporal trends and associated risk factors for newly diagnosed syphilis in PLWHIV in the period 2018 to 2021. Materials and methods: Incident syphilis infection occurring in PLWHIV were reviewed from the electronic database at UHID. New syphilis cases were defined based on a combination of established laboratory parameters as well as clinical diagnoses. All adults (≥18 years) followed at UHID for at least 1 year with at least one contact between 1 January 2018 and 31 December 2021 were included in this study (N = 1315). The observation period ended with the last date of contact or 31 December 2021. We calculated the annual incidence density of syphilis diagnoses and performed Poisson GEE regression analysis for factors related to new syphilis diagnoses and testing. Results: Of 1315 PLWHIV, 1184 (90.2%) were men, median age was 42.0 (34.9 to 51.1) years (Table 1). Two hundred and eleven PLWHIV had a total of 271 new syphilis diagnoses during 4740.1 years of follow-up. Of 271 events, 128 (47.2%) were first syphilis diagnoses, and 162 (59.8%) had symptomatic syphilis (secondary, n = 97). The overall syphilis incidence was 5.7 (95% CI 5.0 to 6.6) per 100 person-years (PY), it increased from 3.2 (95% CI 2.3 to 4.5) to 8.2 (95% CI 6.8 to 10.0) per 100 PY during 2018 to 2021 (Figure 1). On adjusted analysis (adjusted for the number of tests and other variables) younger age, calendar year, MSM risk was associated with syphilis, the association with living in Zagreb was less pronounced (Figure 1). The rate of syphilis testing doubled between 2018 (50.4, 95% CI 56.5 to 64.6 per 100 PY) and 2021 (123.0, 95% CI 118.1 to 128.1 per 100 PY). Factors related to the frequency of syphilis testing were: age, calendar year, MSM risk, and living in Zagreb (Figure 1). Conclusions: During the COVID-19 epidemic years, the incidence rate of syphilis was more than 2 times higher than in previous years reflecting ongoing sexual risk in predominantly younger MSM and highlighting the need for enhanced prevention interventions. References: 1. European Centre for Disease Prevention and Control/WHO Regional Office for Europe. HIV/AIDS surveillance in Europe 2021 – 2020 data. Stockholm: ECDC ; 2021. 2. Bogdanić N, Bendig L, Lukas D, Zekan Š, Begovac J. Timeliness of antiretroviral therapy initiation in the era before universal treatment. Sci Rep. 2021:11:10508.

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: In countries with limited resources, people living with HIV (PLWH) may differently present lung infections hindering the differential diagnosis and the choice of treatment during coronavirus disease 2019 (COVID-19). This study aims to investigate the association between radiological changes and poor COVID-19 outcome PLWH from Central and Eastern Europe. Methods: Since November 2020 ECEE Network Group have started collecting data on HIV/COVID-19 co- infection. In total data was submitted from 16 countries (eCRF) on 557 HIV+ patients. Analysis included patients with radiological examination performed. Logistic regression models were used to identify factors associated with death, ICU admission or partial recovery (poor COVID-19 outcome). Factors significant in univariate models (p

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