Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial

Background: Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH. Methods: The TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness. Discussion: This is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines. Trial registration: ClinicalTrials.gov NCT05221411 . Retrospectively registered on 3 February 2022; EudraCT number 2021–003420-33. Prospectively registered on 16 June 2021

De epidemiologie van AIDS in Nederland bij personen geïnfecteerd door heteroseksueel contact

Tien jaar na het begin van de AIDS-epidemie in Nederland is het aandeel van personen geïnfecteerd door heteroseksueel contact op het totale aantal diagnosen ‘AIDS’ gering (7,4). Tot december 1991 waren er cumulatief 55 vrouwen en 93 mannen in Nederland gerapporteerd met de diagnose, besmet door heteroseksueel contact. Van de 55 heteroseksuele vrouwen had 69 de Nederlandse nationaliteit, van de 93 heteroseksuele mannen 67. Zowel bij de mannen (47) als bij de vrouwen (45) werd een belangrijk deel van het aantal AIDS-patiënten in deze groep gediagnostiseerd in de 4 grote steden (Amsterdam, Rotterdam, Den Haag en Utrecht). De overige AIDS-diagnosen in deze groep werden verspreid over het hele land gesteld. Bij de heteroseksuele vrouwen was er, vanaf 1985, een geleidelijke toename te constateren in het aantal gediagnostiseerde AIDS-gevallen. Bij de mannen was er, vanaf 1984, geen duidelijke trend in het aantal diagnosen waar te nemen. Van de 55 vrouwen waren er 19 afkomstig uit een voor AIDS endemisch gebied of hadden seksueel contact gehad met een persoon uit een dergelijk gebied (34,6). Bij de 93 mannen kwam dit aantal op 29 (31,2). Van 19 van de 55 vrouwen (34,6) was bekend dat zij seksueel contact hadden met een persoon uit de bekende risicogroepen. Ditzelfde gold voor 12 mannen (12,9). Van de overige 17 vrouwen (30,9) en 52 mannen (55,9) was alleen bekend dat zij heteroseksueel waren zonder verdere risicofactoren of risicocontacten. Gezien het nog geringe aantal AIDS-diagnosen onder heteroseksuele personen in Nederland, kan het waarschuwen van (vroegere) seksuele partners van personen met AIDS een belangrijke functie hebben in het voorkómen van verdere verspreiding van HIV in Nederland onder heteroseksuelen. Invoering van een dergelijk waarschuwingsprogramma dient voor het hele land plaats te vinden

Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study):a study protocol for a phase III, open-label, multicentre, randomised controlled trial

Background: Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH. Methods: The TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness. Discussion: This is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines. Trial registration: ClinicalTrials.gov NCT05221411 . Retrospectively registered on 3 February 2022; EudraCT number 2021–003420-33. Prospectively registered on 16 June 2021.</p

Prevalence and risk factors of HSV-1 and HSV-2 antibodies in european HIV infected women

Objectives: To investigate the prevalence and risk factors of HSV-1 and HSV-2 antibodies in HIV infected women and the association between recurrent genital ulcerations and HIV disease progression in HSV-2 positive women. Methods: The presence of HSV antibodies was tested in 276 of the 487 women participating in a European cohort study of HIV infected women. Prevalence rate ratios described the association between HSV infection and its risk factors, using log binomial regression. Generalised estimating equations (GEE) analysis was performed to determine the impact of markers of HIV disease progression on recurrent genital ulcerations. Results: The prevalence of HSV-1 and HSV-2 antibodies was 76% (95% confidence interval (95% CI): 71-81) and 42% (95% CI: 36-50); 30% (95% CI: 24-35) of the women had antibodies against both HSV-1 and HSV-2. The prevalence of HSV-1 was 86% (95% CI: 80-92) in southern Europe compared with 69% (95% CI: 57-79) and 67% (95% CI: 55-77) in central and northern Europe (p=0.002). This geographical variation remained after adjustment for other risk factors. An increasing number of years of sexual activity (p=0.0002) and a history of prostitution (p=0.0001) were independently associated with HSV-2 prevalence. In HSV-2 positive women, symptomatic cases of HSV infection were minimal, but increased with decreasing CD4 count. Conclusion: In HIV infected women, the prevalence of HSV antibodies is high and symptomatic cases of HSV infection are minimal, but increase with decreasing CD4 count. HSV-2 but not HSV-1 was related to sexual behaviour (that is, a history of prostitution and the number of sexually active years) in this group of HIV infected women