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W. M. Han, B. Neesgaard, M. Knappik, M. Cavassini, I. Abela, A. Timiryasova, L. Greenberg, Charlotte Martin et al.

Summary Background Data on cancer incidence and associated risk factors among women with HIV are limited. We investigated cancer burden among women with HIV. Methods We included all women ≥18 years from the two large multicentre observational cohort collaborations (D:A:D and RESPOND). The primary outcomes were incidence of all cancers, HPV-related and common individual cancers including breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL) from 2006 to 2021. Baseline was defined as the latest date of entry into local cohort enrolment and 1st January 2006 for D:A:D and 1st January 2012 for RESPOND. Participants were followed from baseline until the date of first cancer, final follow-up or administrative censoring—whichever occurred first. We assessed risk factors using multivariable Poisson regression by applying robust standard errors and determined a population attributable fraction (PAF) for key risk factors for cancers. Findings Among 17,512 women included, median age at baseline was 39.5 years (interquartile range, IQR 32.5–46.0). Over 141,404 person-years (PYS) and a median 9.2 (5.5–10.1) years of follow-up, 832 women were diagnosed with any cancer; incidence rate 5.9 (95% CI 5.5–6.4)/1000 PYS, 163 HPV-related cancers (1.1 [1.0–1.3]/1000 PYS), 150 breast cancers (1.1 [0.9–1.2]/1000 PYS), 94 lung cancers (0.7 [0.5–0.8]/1000 PYS) and 72 NHL (0.5 [0.4–0.6]/1000 PYS). Older age (≥45 vs. <45 years), Southern Europe (vs. Western Europe) and smoking were associated with an increased risk of overall cancers. Lower pre-ART nadir CD4, time-updated CD4, and a prior AIDS diagnosis were associated with lung- and HPV-related cancer. In PAF analysis, smoking and HIV-related factors such as lower current CD4, nadir CD4 and HIV viremia significantly contributed to cancer risk. Interpretation Our findings suggest that women with HIV older than 45 years, past or current immunosuppressed or current smokers could be candidates for intensified cancer screening and prevention. Funding The Highly Active Antiretroviral Therapy Oversight Committee, The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The 10.13039/100025411Isabel Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, 10.13039/100010877ViiV Healthcare, and Gilead Sciences.

A. Skrzat-Klapaczyńska, Botond Lakatos, G. Dragović, V. Mulabdic, C. Oprea, D. Gokengin, A. Verhaz, I. Alexiev et al.

The Central and Eastern Europe (CEE) region differs in access to HIV and co-infections care and treatment. The aim of the study was to analyze the relation between the severity of the COVID-19 disease and HIV specific factors in the European Union (EU) Countries and in non-European Union (non-EU) Countries.The study was conducted between November 2020 and May 2021. Euroguidelines in Central and Eastern Europe (ECEE) Network Group was collecting observational data on HIV-positive patients diagnosed with COVID-19. In total, 16 countries from CEE (Poland, Czech Republic, Ukraine, Croatia, Turkey, Romania, Belarus, Estonia, Lithuania, Greece, Georgia, Albania, Hungary, Serbia, Bosnia and Herzegovina, and Bulgaria) submitted data on HIV-positive patients using an electronic case report form (eCRF). Chi-Square test was used for group comparisons.In total 557 patients were included into the analyses: 361 from EU and 196 from non-EU countries. Access to remdesivir was 1.5% in non-EU countries vs 3.9% in EU-countries (p= 0.1952) . Symptoms of COVID-19 occurred more often in non-EU countries (93.3%) vs non-EU countries (83.6%) [p=0.0009], as well as hospitalization 32.8% vs. 20.8% respectively [0.0027]. Death/ICU was 4.8% in non-EU countries vs 3.4% in EU-countries (p=0.4877). In total 18 (3.23%) patients found out about HIV diagnosis during COVID-19, which was comparable in two groups (11 [3.0%] in UE countries vs. 7 [3.6%] in non-UE countries; p=0.8029).Patients from non- EU countries were more likely to be COVID-19 symptomatic and hospitalized. Access to antiviral therapy for SARS-CoV-2 was very low for all CEE countries.

I. Ianache, A. Skrzat-Klapaczyńska, D. Jilich, L. Fleischhans, I. Gmizić, J. Ranin, Antonios Papadopoulos, K. Protopapas et al.

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.

C. Kraef, Sabine Singh, O. Fursa, A. Abutidze, N. Rukhadze, V. Mulabdic, N. Yancheva, Murat Mehmeti et al.

We aimed to assess the extent of integration of non‐communicable disease (NCD) assessment and management in HIV clinics across Europe.

Kersti Aimla, J. Kowalska, R. Matulionytė, V. Mulabdic, A. Vassilenko, N. Bolokadze, D. Jilich, S. Antoniak et al.

(1) Background: Viral hepatitis C (HCV) and viral hepatitis B (HBV) are common co-infections in people living with HIV (PLWH). All PLWH should be vaccinated against HBV and hepatitis A (HAV) and treated for HBV and HCV. We aimed to compare testing, prophylaxis and treatment of viral hepatitis in PLWH in Central and Eastern Europe (CEE) in 2019 and 2022. (2) Methods: Data was collected through two on-line surveys conducted in 2019 and 2022 among 18 countries of the Euroguidelines in CEE (ECEE) Network Group. (3) Results: In all 18 countries the standard of care was to screen all PLWH for HBV and HCV both years; screening of HAV was routine in 2019 in 54.5% and in 2022 47.4% of clinics. Vaccination of PLWH against HAV was available in 2019 in 16.7%, in 2022 in 22.2% countries. Vaccination against HBV was available routinely and free of charge in 50% of clinics both in 2019 and 2022. In HIV/HBV co-infected the choice of NRTI was tenofovir-based in 94.4% of countries in both years. All clinics that responded had access to direct-acting antivirals (DAAs) but 50% still had limitations for treatment. (4) Conclusions: Although testing for HBV and HCV was good, testing for HAV is insufficient. Vaccination against HBV and especially against HAV has room for improvement; furthermore, HCV treatment access needs to overcome restrictions.

D. Gokengin, D. Bursa, A. Skrzat-Klapaczyńska, I. Alexiev, Elena Arsikj, T. Balayan, J. Begovac, Alma Čičić et al.

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

A. Papadopoulos, K. Thomas, K. Protopapas, S. Antonyak, J. Begovac, G. Dragović, D. Gökengin, Kersti Aimla et al.

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.

D. Jilich, A. Skrzat-Klapaczyńska, L. Fleischhans, D. Bursa, S. Antoniak, T. Balayan, J. Begovac, Alma Čičić et al.

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.

L. Greenberg, L. Ryom, B. Neesgaard, G. Wandeler, T. Staub, M. Gisinger, Michael Skoll, H. Günthard et al.

BACKGROUND Limited data exist comparing clinical outcomes of two-drug regimens (2DRs) and three-drug regimens (3DRs) in people living with HIV. METHODS Antiretroviral treatment-experienced individuals in RESPOND switching to a new 2DR or 3DR from 1/1/12-1/10/18 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median 52.6 years [interquartile range 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%).There were 619 events during 27,159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU [95% CI 20.7-24.5]) on 3DRs, 79 (30.9/1000 PYFU [24.8-38.5]) on 2DRs. The most common events were death (7.5/1000 PYFU [95% CI 6.5-8.6]) and non-AIDS cancer (5.8/1000 PYFU [4.9-6.8]). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio: 0.92 [0.72-1.19]; p=0.53). CONCLUSIONS This is the first large, international cohort assessing clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes; further research on resistance barriers and long-term durability of 2DRs is needed.

J. Kowalska, A. Skrzat-Klapaczyńska, D. Bursa, T. Balayan, Josip Begovac, N. Chkhartishvili, D. Gökengin, A. Harxhi et al.

J. Kowalska, A. Skrzat-Klapaczyńska, D. Bursa, T. Balayan, Josip Begovac, N. Chkhartishvili, D. Gökengin, A. Harxhi et al.

Introduction The SARS-CoV-2 pandemic has hit the European region disproportionately. Many HIV clinics share staff and logistics with infectious disease facilities, which are now on the frontline in tackling COVID-19. Therefore, this study investigated the impact of the current pandemic situation on HIV care and continuity of antiretroviral treatment (ART) supplies in CEE countries. Methods The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was established in February 2016 to review standards of care for HIV in the region. The group consists of professionals actively involved in HIV care. On March 19, 2020 we decided to review the status of HIV care sustainability in the face of the emerging SARS-CoV-2 pandemic in Europe. For this purpose, we constructed an online survey consisting of 23 questions. Respondents were recruited from ECEE members in 22 countries, based on their involvement in HIV care, and contacted via email. Results In total, 19 countries responded: Albania, Armenia, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Greece, Hungary, Lithuania, Macedonia, Poland, Republic of Moldova, Russia, Serbia, Turkey, and Ukraine. Most of the respondents were infectious disease physicians directly involved in HIV care (17/19). No country reported HIV clinic closures. HIV clinics were operating normally in only six countries (31.6%). In 11 countries (57.9%) physicians were sharing HIV and COVID-19 care duties. None of the countries expected shortage of ART in the following 2 weeks; however, five physicians expressed uncertainty about the following 2 months. At the time of providing responses, ten countries (52.6%) had HIV-positive persons under quarantine. Conclusions A shortage of resources is evident, with an impact on HIV care inevitable. We need to prepare to operate with minimal medical resources, with the aim of securing constant supplies of ART. Non-governmental organizations should re-evaluate their earlier objectives and support efforts to ensure continuity of ART delivery.

J. Kowalska, D. Bursa, D. Gökengin, D. Jilich, J. Tomažič, M. Vasylyev, P. Bukovinowa, V. Mulabdic et al.

Pre‐exposure prophylaxis (PrEP) for HIV infection has been introduced in only a few European countries. We investigated the potential to provide PrEP in the Central and Eastern European region, and in neighbouring countries.

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