Incidence and risk factors for HIV-tuberculosis coinfection in the Cologne-Bonn region: a retrospective cohort study.

PURPOSE: The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. METHODS: We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. RESULTS: During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously. CONCLUSION: Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries.

Torque Teno Virus load is associated with CDC stage and CD4+ cell count in people living with HIV but unrelated to AIDS-defining events and Human Pegivirus load.

BACKGROUND: Torque Teno Virus (TTV) is a non-enveloped, circular single-strand DNA virus and part of the human virome. The replication of TTV was related to the immune status in patients treated with immunosuppressive drugs after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH). METHODS: In this analysis serum samples of PLWH from the RESINA multicenter cohort were reanalysed for TTV. Investigated clinical and epidemiological parameters included Pegivirus (HPgV) load, age, sex, HIV load, CD4+ cell count (CDC 1, 2, 3) and CDC clinical stages (1993 CDC classification system, A, B, C) before initiation of antiretroviral treatment. Regression analysis was used to detect possible associations among parameters. RESULTS: Our analysis confirmed TTV as a strong predictor of CD4+ cell count and CDC class 3. This relationship was used to propose a first classification of TTV load in regard to clinical stage. We found no association with clinical CDC stages A, B and C. HPgV load was inversely correlated with HIV load but not TTV load. CONCLUSIONS: TTV load was associated with immunodeficiency in PLWH. Neither TTV- nor HIV load were predictive for the clinical categories of HIV infection.

A fatal course of COVID-19 during the Omicron surge: can you estimate your patients' SARS-CoV-2 immune status?

We present a case of an ultimately fatal course of COVID-19 (coronavirus disease-19) in an 81-year-old female patient during the Omicron surge. The patient did not represent the typical patient at risk for severe COVID-19 with significant causes of immunodeficiency. However, she had been skeptical about the vaccination for severe acute respiratory syndrome virus-2 (SARS-CoV-2) and had refused it. Moreover, there had been no previous COVID-19 episodes. Our case report illustrates that with regard to SARS-CoV-2, immunologically naive patients are still at risk for severe and/or even fatal courses of COVID-19. We call to implement both, recommendations for SARS-CoV-2 vaccinations as well as for antiviral treatment.

Pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH) in the German CAPNETZ-Cohort.

OBJECTIVES: The objective of this study was to identify the pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH), and to compare it with a matched HIV negative group in order to reassess therapeutic strategies for PLWH. METHODS: Seventy-three (n = 73) PLWH (median CD4 3-6 months before CAP: 515/µl; SD 309) with community acquired pneumonia (CAP) were matched with 218 HIV-negative CAP controls in a prospective study design. Pathogen identifications used blood culture, samples from the upper and lower respiratory tract (culture and multiplex PCR) and urinary pneumococcal and legionella antigen test. RESULTS: Although the vaccination rate among PLWH with CAP was significantly higher (pneumococcal vaccination: 27.4 vs. 8.3%, p < 0.001; influenza vaccination: 34.2 vs. 17.4%, p = 0.009), pneumococci were found most frequently as pathogen among both PLWH (n = 19/21.3%) and controls (n = 34/17.2%; p = 0.410), followed by Haemophilus influenzae (PLWH, n = 12/13.5%, vs. controls, n = 25 / 12.6%; p = 0.850). Staphylococcus aureus was found equally in 20.2 and 19.2% in PLWH and controls, but infection or colonization could not be distinguished. Mortality during 6-month follow-up was significantly higher for PLWH (5/73, or 6.8%) versus controls (3/218, or 1.4%), however with lower case numbers than previously reported. Typical HIV-associated pathogens such as Pneumocystis jirovecii were found only exceptionally. CONCLUSIONS: Our study underscores the persistent clinical burden of CAP for PLWH. From pathogen perspective, empirical antibiotic treatment for CAP in PLWH on antiretroviral therapy should cover pneumococci and Haemophilus influenzae and may be adopted from valid common recommendations.

Early combination therapy of COVID-19 in high-risk patients.

PURPOSE: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect. METHODS: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 106 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 106 copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher's tests or Kaplan-Meier analysis and long-rank tests. Multivariable regression analysis was performed. RESULTS: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 106 copies/ml of 8.0 days (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2-9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment. CONCLUSION: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.

Deficient Immune Response following SARS-CoV-2 Vaccination in Patients with Hepatobiliary Carcinoma: A Forgotten, Vulnerable Group of Patients.

Introduction: Data on immune response rates following vaccination for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients with hepatobiliary carcinoma (HBC) are rare. However, impaired immunogenicity must be expected due to the combination of chronic liver diseases (CLDs) with malignancy and anticancer treatment. Methods: In this prospective, longitudinal study, 101 patients were included, of whom 59 were patients with HBC under anticancer treatment. A cohort of patients with a past medical history of gastrointestinal cancer, of whom 28.6% had HBC without detectable active tumor disease having been off therapy for at least 12 months, served as control. Levels of SARS-CoV-2 anti-spike IgG, surrogate neutralization antibodies (sNABs), and cellular immune responses were compared. In uni- and multivariable subgroup analyses, risk factors for impaired immunogenicity were regarded. Data on rates and clinical courses of SARS-CoV-2 infections were documented. Results: In patients with HBC under active treatment, levels of SARS-CoV-2 anti-spike IgG were significantly lower (2.55 log10 BAU/mL; 95% CI: 2.33-2.76; p < 0.01) than in patients in follow-up care (3.02 log10 BAU/mL; 95% CI: 2.80-3.25) 4 weeks after two vaccinations. Antibody levels decreased over time, and differences between the groups diminished. However, titers of SARS-CoV-2 sNAB were for a longer time significantly lower in patients with HBC under treatment (64.19%; 95% CI: 55.90-72.48; p < 0.01) than in patients in follow-up care (84.13%; 95% CI: 76.95-91.31). Underlying CLD and/or liver cirrhosis Child-Pugh A or B (less than 8 points) did not seem to further impair immunogenicity. Conversely, chemotherapy and additional immunosuppression were found to significantly reduce antibody levels. After a third booster vaccination for SARS-CoV-2, levels of total and neutralization antibodies were equalized between the groups. Moreover, cellular response rates were balanced. Clinically, infection rates with SARS-CoV-2 were low, and no severe courses were observed. Conclusion: Patients with active HBC showed significantly impaired immune response rates to basic vaccinations for SARS-CoV-2, especially under chemotherapy, independent of underlying cirrhotic or non-cirrhotic CLD. Although booster vaccinations balanced differences, waning immunity was observed over time and should be monitored for further recommendations. Our data help clinicians decide on individual additional booster vaccinations and/or passive immunization or antiviral treatment in patients with HBC getting infected with SARS-CoV-2.

Major revision version 12.0 of the European AIDS Clinical Society guidelines 2023.

BACKGROUND: The European AIDS Clinical Society (EACS) guidelines were revised in 2023 for the 19th time, and all aspects of HIV care were updated. KEY POINTS OF THE GUIDELINES UPDATE: Version 12.0 of the guidelines recommend the same six first-line treatment options for antiretroviral treatment (ART)-naïve adults as versions 11.0 and 11.1: tenofovir-based backbone plus an unboosted integrase inhibitor or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with lamivudine or emtricitabine plus dolutegravir. The long-acting section has been expanded in the ART and drug-drug interaction (DDI) panels. Tables for preferred and alternative ART in children and adolescents have been updated, as has the section on prevention of vertical transmission, particularly with new guidance for breastfeeding. A new DDI table has been included for the ART and anti-infective drugs used for opportunistic infections, sexually transmitted infections, and other infectious conditions; lenacapavir has been included in all DDI tables. New sections on alcohol use and patient-reported outcome measures (PROMs) have been included in the comorbidity panel, in addition to updates on many relevant topics, such as new resource guidance for deprescribing in people with HIV. Other sections, including travel, cognitive impairment, cancer screening, sexual health, and diabetes have also been revised extensively. The algorithm for the management of acute hepatitis C virus infection has been removed, as current guidelines recommend immediate treatment of all people with recently acquired hepatitis C virus. Updates on vaccination for hepatitis B virus and recommendations for simplification to tenofovir-free two-drug regimens in people with isolated anti-hepatitis B core antibodies are provided. In the opportunistic infections and COVID-19 panel, guidance on the management of COVID-19 in people with HIV has been updated according to the most up-to-date evidence, and a new section on monkeypox has been added. CONCLUSIONS: In 2023, the EACS guidelines were updated extensively and now include several new sections. The recommendations are available as a free app, in interactive web format, and as a pdf online.

Optimization of HIV testing services in Germany using HIV indicator diseases: study protocol of the HeLP study.

BACKGROUND: Despite the potentially accompanying negative clinical, epidemiologic, and health economic effects, a large proportion of persons living with the human immunodeficiency virus (HIV) are diagnosed late. Internationally, numerous diseases are known to be HIV indicator diseases. Adequate HIV testing in the presence of HIV indicator diseases could help to diagnose unknown HIV infections earlier. The objective of the HeLP study is to validate published HIV indicator diseases for the German setting and to identify guidelines in terms of these indicator diseases in order to reduce knowledge gaps and increase HIV testing when HIV indicator diseases are diagnosed. METHODS: A mixed methods approach is used. In a first step, published HIV indicator diseases will be identified in a systematic literature review and subsequently discussed with clinical experts regarding their relevance for the German setting. For the validation of selected indicator diseases different data sets (two cohort studies, namely HIV-1 seroconverter study & ClinSurv-HIV, and statutory health insurance routine data) will be analyzed. Sensitivity analyses using different time periods will be performed. Guidelines of HIV indicator diseases validated in the HeLP study will be reviewed for mentioning HIV and for HIV testing recommendations. In addition, semi-standardized interviews (followed by a free discussion) with guideline creators will identify reasons why HIV testing recommendations were (not) included. Subsequently, a random sample of physicians in medical practices will be surveyed to identify how familiar physicians are with HIV testing recommendations in guidelines and, if so, which barriers are seen to perform the recommended tests in everyday care. DISCUSSION: The HeLP-study adopts the challenge to validate published HIV indicator diseases for the German setting and has the potential to close a knowledge gap regarding this objective. This has the potential to improve targeted HIV testing for patients with HIV indicator diseases and consequently lead to earlier HIV diagnosis. TRIAL REGISTRATION: DRKS00028743.

The DoDo experience: an alternative antiretroviral 2-drug regimen of doravirine and dolutegravir.

BACKGROUND: Currently available antiretroviral 2-drug regimen (2DR) fixed dose combinations may not be suitable for specific situations including the presence of resistance associated mutations (RAM) or drug - drug interactions (DDI). The data on the use of the non-nucleoside reverse transcriptase inhibitor doravirine (DOR) and the integrase inhibitor dolutegravir (DTG) as an alternative 2DR remain scarce. METHODS: People living with HIV with DOR + DTG as a 2DR are being followed in a prospective observational study. RESULTS: This analysis describes 85 participants with a median age of 57 years. Median CD4-nadir was 173/µl and a majority (66%) had a history of HIV-associated or AIDS-defining conditions. Antiretroviral history was mostly extensive, and documentation of RAM was frequent. The main reasons for choosing DOR + DTG were DDI (29%), tolerability (25%), and cardiovascular risk reduction (21%). Plasma viral load at switch was < 50 copies/ml in all but 3 instances, median CD4 count was 600/µl. DOR + DTG was later changed to another regimen in 10 participants after a median of 265 days, the other 75 participants have remained on DOR + DTG for a median of 947 days. CONCLUSION: DOR + DTG as a 2DR proved to be a durable treatment option even in extensively pretreated individuals.

Impaired immunogenicity after vaccination for SARS-CoV-2 in patients with gastrointestinal cancer: does tumor entity matter?

Background: SARS-CoV-2 immunogenicity in patients with gastrointestinal cancer (GI cancer) following second and third vaccination was analyzed. Methods: A total of 125 patients under active anticancer therapy or in follow-up care were included in this prospective study. Seroprevalence of SARS-CoV-2 anti-spike and surrogate neutralization antibodies (NABs) was measured. Results: Four weeks after second vaccination, adequate titers of SARS-CoV-2 anti-spike immunoglobulin G (IgG) [≥282.0 binding antibody units (BAU)/mL] were found in 62.2% of patients under treatment versus 96.3% of patients in follow-up care (P<0.01). Sufficient titers of SARS-CoV-2 surrogate NAB (≥85.0%) were found in 32.7% of patients under treatment versus 70.6% in follow-up care (P<0.01). Titers of SARS-CoV-2 anti-spike IgG were especially low in patients with colorectal cancer (CRC). For SARS-CoV-2 surrogate NAB, patients with hepatocellular carcinoma (HCC) and with pancreaticobiliary cancer showed the lowest titers (P<0.01). SARS-CoV-2 anti-spike IgG and SARS-CoV-2 surrogate NAB were associated with a correlation coefficient of 0.93. Reaching a titer of SARS-CoV-2 anti-spike IgG ≥482.0 BAU/mL, protective levels of SARS-CoV-2 surrogate NAB (≥85.0%) could be assumed. Following booster vaccination, all patients reached effective antibody titers. Conclusions: Patients with active GI cancer showed impaired immunogenicity after second SARS-CoV-2 vaccination which was overcome by booster vaccination. Our findings were tumor-related and pronounced in patients with CRC and HCC. Waning immunity over time and antibody escape phenomena by variant of concern Omicron must be considered in these especially vulnerable patients.

Prevalence, characteristics and challenges of late HIV diagnosis in Germany: an expert narrative review.

PURPOSE: We aimed to review the landscape of late HIV diagnosis in Germany and discuss persisting and emerging barriers to earlier diagnosis alongside potential solutions. METHODS: We searched PubMed for studies informing the prevalence, trends, and factors associated with late HIV diagnosis in Germany. Author opinions were considered alongside relevant data. RESULTS: In Germany, older individuals, heterosexuals, and migrants living with HIV are more likely to be diagnosed late. The rate of late diagnosis in men who have sex with men (MSM), however, continues to decrease. Indicator conditions less often prompt HIV testing in women and non-MSM. During the COVID-19 pandemic, the absolute number of late diagnoses fell in Germany, but the overall proportion increased, probably reflecting lower HIV testing rates. The Ukraine war and subsequent influx of Ukrainians living with HIV may have substantially increased undiagnosed HIV cases in Germany. Improved indicator testing (based on unbiased assessments of patient risk) and universal testing could help reduce late diagnoses. In patients who receive a late HIV diagnosis, rapid treatment initiation with robust ART regimens, and management and prevention of opportunistic infections, are recommended owing to severely compromised immunity and increased risks of morbidity and mortality. CONCLUSION: Joint efforts are needed to ensure that UNAIDS 95-95-95 2030 goals are met in Germany. These include greater political will, increased funding of education and testing campaigns (from government institutions and the pharmaceutical industry), continued education about HIV testing by HIV experts, and broad testing support for physicians not routinely involved in HIV care.

Tecovirimat for the treatment of severe Mpox in Germany.

BACKGROUND: In May 2022, a multi-national mpox outbreak was reported in several non-endemic countries. The only licensed treatment for mpox in the European Union is the orally available small molecule tecovirimat, which in Orthopox viruses inhibits the function of a major envelope protein required for the production of extracellular virus. METHODS: We identified presumably all patients with mpox that were treated with tecovirimat in Germany between the onset of the outbreak in May 2022 and March 2023 and obtained demographic and clinical characteristics by standardized case report forms. RESULTS: A total of twelve patients with mpox were treated with tecovirimat in Germany in the study period. All but one patient identified as men who have sex with men (MSM) who were most likely infected with mpox virus (MPXV) through sexual contact. Eight of them were people living with HIV (PLWH), one of whom was newly diagnosed with HIV at the time of mpox, and four had CD4+ counts below 200/µl. Criteria for treatment with tecovirimat included severe immunosuppression, severe generalized and/or protracted symptoms, a high or increasing number of lesions, and the type and location of lesions (e.g., facial or oral soft tissue involvement, imminent epiglottitis, or tonsillar swelling). Patients were treated with tecovirimat for between six and 28 days. Therapy was generally well-tolerated, and all patients showed clinical resolution. CONCLUSIONS: In this cohort of twelve patients with severe mpox, treatment with tecovirimat was well tolerated and all individuals showed clinical improvement.

Enabling CAR T-cell therapies for HIV-positive lymphoma patients - A call for action.

People living with HIV have a higher risk of developing lymphoma. Outcomes for people living with HIV with relapsed or refractory (r/r) lymphoma remain poor. For this group of patients, chimeric antigen receptor (CAR) T-cell therapy represents a new successful treatment strategy. However, people living with HIV were not included in pivotal trials, so data are limited to case reports. We searched the PubMed and Ovid technologies databases for literature until 1 November 2022 using the terms 'HIV and CAR-T', 'HIV and lymphoma' and 'HIV and CAR-T and lymphoma'. Six cases with sufficient information were included in the review. The mean CD4+ T-cell count before CAR T-cell therapy was 221 cells/µL (range 52-629). The viral load was below the limit of detection in four patients. All patients had diffuse large B-cell lymphoma (DLBCL) and were treated with gamma-retroviral-based axicabtagene ciloleucel. Four patients developed cytokine-release syndrome (CRS) grade 2 or less or immune effector-cell-associated neurotoxicity syndrome (ICANs) grade 3-4. Four of six patients responded to CAR T-cell therapy (three complete remissions, one partial remission). In summary, there are no clinical reasons to restrict the use of CAR T-cell therapy in people living with HIV with r/r DLBCL. According to the current data, CAR T-cell therapy was safe and effective. In people who meet the standard criteria for CAR T-cell therapy, this treatment approach could significantly improve the unmet need for more effective treatment options for people living with HIV with r/r lymphoma.

Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis.

BACKGROUND: Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. METHODS: For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. FINDINGS: The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. INTERPRETATION: Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. FUNDING: National Institutes of Health and Dr. C.J. Vaillant Fonds.

People living with HIV, HCV and HIV/HCV coinfection in intensive care in a German tertiary referral center 2014-2019.

PURPOSE: The epidemiology of HIV-infected individuals on the Medical Intensive Care Units (MICU) has changed after profound progress in treatment of AIDS-defining illnesses and anti-retroviral therapy (ART). Changes of MICU utilization of Hepatitis C (HCV) patients following roll-out of direct-acting antivirals (DAA) are yet to evaluate. METHODS: We performed a retrospective study on all patients with HIV, HIV/HCV and HCV admitted to the MICU of University Hospital Bonn 2014-2019. We assessed sociodemographic data, available clinical data from HIV patients (CDC stage, CD4 + lymphocyte cell count, HIV-1-RNA, ART) and HCV patients (HCV-RNA, stage of liver cirrhosis, treatment history) and outcome. RESULTS: 237 patients (46 HIV, 22 HIV/HCV, 169 HCV; 168 male, median age 51.3 years) with 325 MICU admissions were included. Admission criteria for HIV patients were infections (39.7% AIDS-associated, 23.8% with controlled HIV-infection) and cardiopulmonary diseases (14.3%). HIV/HCV coinfected patients had infections in controlled/uncontrolled HIV-infection (46.4%), cardiopulmonary diseases and intoxication/drug abuse (17.9% each). Reasons for HCV-mono-infected patients were infections (24.4%), sequelae of liver disease (20.9%), intoxication/drug abuse (18.4%) and cardiopulmonary diseases (15%). 60 patients deceased; most important risk factor was need for mechanical ventilation. The number of HCV-patients admitted to MICU with chronic active disease and sequelae of liver disease decreased while the proportion of patients with completed DAA-treatment increased. CONCLUSION: Infections remain the most important reason for MICU admission in patients with HIV and/or HCV infection while non-AIDS related conditions increased. DAA roll-out has a beneficial effect on liver-associated morbidity in HCV patients admitted to MICU.

Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV.

BACKGROUND AND AIMS: Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis. METHODS: This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA. RESULTS: Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis. CONCLUSION: Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease.