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Introduction. Non-alcoholic steatohepatitis (NASH) is of concern in an aging and antiretroviral therapy (ART)-pretreated HIV-infected population. No therapeutic agent has yet been licensed for the treatment of NASH in order to reduce hepatic inflammation, steatosis, or liver fibrosis. The CCR5 receptor antagonist maraviroc is an approved HIV drug, but hepatic CCR5 inhibition has also been suggested to reduce hepatic inflammation and fibrogenesis in animal models. This study aimed to investigate the impact of a maraviroc add-on strategy on hepatic inflammation in ART-treated HIVmono-infected individuals with NASH. Methods. The MASH study (Maraviroc-Add on for Steatohepatitis in HIV infected patients) was a single-arm, open-label trial conducted across 5 sites in Germany and the United Kingdom. HIV-infected individuals with biopsy proven NASH were invited to add maraviroc BID to their existing, suppressive ART regimen for 48 weeks, and undergo a second liver biopsy thereafter. Patients had immunologic, cytokine, metabolic, and histologic assessment at baseline and end of treatment (EOT). Results. Overall, 24 subjects were screened, and 13 completed the study and were analyzed. All participants were male, median age 50.5 years [45.5-55.5], baseline BMI 30.66 kg/m2 [27.92-33.63]; 83.3% (10/12) had insulin resistance. At baseline, 11/13 patients (85%) had fibrosis >1 (Metavir). At EOT no significant changes in the hepatic immune cell infiltrate (CD4/CD8/CD68) were observed, however, the NAS score decreased non significantly from 4.077 ± 0.76 at baseline to 3.64 ± 0.51 at EOT (p = 0.125). At week 48, 7/11 patients (63%) showed significant fibrosis> stage 1, EOT BMI was similar compared to baseline. Add-on MVC had no significant impact on inflammatory markers or lipid metabolism.

The unprecedented global scale of COVID‐19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarise the evidence for antiretrovirals to treat COVID‐19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.

Objectives. The objective of the paper is to present the outcomes of the HepHIV 2019 conference, held in Bucharest under the Romanian EU Presidency and focusing on challenges of timely and integrated testing and care. Methods. The conference programme was put together by the organizing committee. It consisted of invited talks and peer-reviewed abstracts. Results. In all, 65 abstracts from 20 countries were presented during the conference, which had nearly 250 delegates, including high-profile political representation. The conference highlighted the need to shift towards further disease integration because of the epidemiological characteristics of the hepatitis B (HBV), hepatitis C (HCV), HIV, sexually transmitted infection (STIs) and tuberculosis (TB) epidemics in the WHO European region. Integration should be a priority in the response to the epidemics to better reach key populations and to ensure better testing coverage. This relates to both the integration of services in shared care models and the integration of different settings and stakeholders in national strategies. Conclusions. The conference demonstrated the need for greater political support for the policy changes required to implement integration. Testing normalization efforts are key to maximizing the impact of integration efforts. The conference call to action can help to guide developments in testing and linkage-to-care interventions across the European region. The HepHIV 2019 Bucharest Conference was co-funded with the Health Programme of the European Union and the EU Health Project Symposium; Integrated Testing and Synergies was funded by the Health Programme of the European Union. The HepHIV 2019 Bucharest Conference was funded by the HIV in Europe/EuroTEST Initiative that received sponsorship funds for this purpose from Gilead, Merck MSD, ViiV Healthcare, Abbvie, Autotest Santé (AAZ-LMB), Cepheid, InTec, OraSure and SH:24. The funders had no role in the study design, analysis, decision to publish, or preparation of the manuscript.

Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P < 0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.

Objectives The aim of the study was to assess the regression of liver stiffness after successful direct-acting antiviral (DAA) treatment in patients with hepatitis C virus (HCV) monoinfection and HCV/-HIV coinfection. In addition, we aimed to identify factors associated with liver stiffness regression. Methods We studied patients treated with interferon-free DAA regimens with a sustained virological response at week 12 (SVR12) or 24 (SVR24) post-treatment. Liver stiffness was assessed by transient elastography (TE) before the initiation and after the end of treatment (median 12 weeks). Results Of 214 enrolled patients, 85 (40%) were HCV monoinfected and 129 (60%) HCV/HIV coinfected. Baseline median TE values were 7.8 kPa [interquartile range (IQR) 5.9-12.0 kPa] in mono-infected patients and 10.7 kPa (IQR 7.8-17.0 kPa) in coinfected patients. Overall, the median TE value decreased from 10.1 to 6.8 kPa (n = 214; P < 0.0001). There was no difference between mono- and coinfected patients (-2.2 versus -3.3 kPa, respectively; P = 0.88), which was verified by an analysis of covariance (ANCOVA) adjusting for baseline TE values. Significant (>= 30%) regression of liver stiffness was achieved by 45% of patients (54% with baseline TE >= 7.1 kPa). In multivariate analysis, a prior HCV treatment was a negative predictor of liver stiffness regression [odds ratio (OR) 0.31; P = 0.001]. A higher baseline TE value was positively associated with achieving a significant regression (OR 1.06; P = 0.02). HIV coinfection status, HCV genotype, age, sex, treatment duration, controlled attenuation parameter value, bilirubin concentration, platelet count and aspartate aminotransferase concentration were not associated with liver stiffness regression. Conclusions Regression of liver stiffness after successful DAA treatment did not differ in patients with HCV monoinfection and those with HCV/HIV coinfection. Half of all patients achieved a significant (>= 30%) regression. Prior treatment for HCV was a negative predictor for this endpoint, while a higher baseline TE value was positively associated with regression.

Contains fulltext : 117827.pdf (Publisher’s version ) (Closed access) OBJECTIVE:: To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum. DESIGN:: A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. METHODS:: HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study. Twenty-four-hour pharmacokinetic curves were recorded in the third trimester (preferably week 33) and postpartum (preferably week 4-6). Collection of a cord blood sample and maternal sample at delivery was optional. Pharmacokinetic parameters were calculated using WinNonlin software version 5.3. Statistical analysis was conducted using SPSS version 16.0. RESULTS:: Thirty-four women were included in the analysis. Geometric mean ratios of third trimester vs. postpartum [90% confidence interval (CI)] were 0.77 (0.71-0.83) for TDF area under the curve (AUC0-24 h); 0.81 (0.68-0.96) for TDF Cmax and 0.79 (0.70-0.90) for TDF C24 h and 0.75 (0.68-0.82) for FTC AUC0-24 h; and 0.87 (0.77-0.99) for FTC Cmax and 0.77 (0.52-1.12) for FTC C24 h. The viral load close to delivery was less than 200 copies/ml in all but one patient, the average gestational age at delivery was 38 weeks. All children were tested HIV-negative and no congenital abnormalities were reported. CONCLUSION:: Although pharmacokinetic exposure of the NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not associated with virological failure in this study and did not result in mother-to-child transmission.

OBJECTIVES: Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. METHODS: HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. RESULTS: A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. CONCLUSIONS: HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype.

Acute hepatitis C virus (AHCV) infections are frequently seen worldwide in certain risk groups with an annual incidence rate varying between 0.08% and 66%. Although this incidence is substantial, a delayed diagnosis during chronic infection is most often made in the absence of clinical symptoms in the acute phase of the infection. Current used methods to diagnose AHCV are IgG antibody seroconversion and repeated HCV RNA measurements though no definite diagnostic test is currently available. Progress in the field of adaptive and innate immune responses has aided to both advancements in the field of HCV vaccine development and a more basic understanding of viral persistence. The rapid changes in the treatment of chronic HCV will affect therapeutic regimens in AHCV in the coming years leading to shorter treatment courses and pegylated interferon-free modalities. This review gives an overview of the current knowledge and uncertainties together with some future perspectives on acute HCV epidemiology, virology, immunology and treatment.

With the availability of all-oral, direct acting antivirals (DAAs), hepatitis C virus (HCV) therapy has been revolutionized for HIV/HCV co-infected patients. Indeed HCV cure rates are now no longer different between HCV mono and HIV/HCV co-infected persons and are both greater than 95%. Therefore, current treatment guidelines no longer separate these two groups. Indications for HCV treatment and choice of DAA combination are now the same for all HCV patients. In HIV/HCV co-infection however, drug interactions between HIV and HCV agents need be checked prior to starting HCV therapy. Finally, the higher risk of hepatic decompensation in HIV/HCV co-infected patients, including those receiving successful antiretroviral therapy, continues to make these patients a high priority group for receiving access to modern DAA combination therapy.

Background & Aims: The efficacy and safety of triple therapy combining boceprevir (BOC) or telaprevir (TVR) with pegylated interferon-alfa and ribavirin (PegIFN/RBV) has rarely been investigated in human immunodeficiency virus/hepatitis C virus (HIV/HCV) genotype 1-coinfected patients with cirrhosis. Methods: We conducted a European (France, Italy, Germany, Netherlands) multicentre study of triple therapy in cirrhotic HIV/HCV GT1-coinfected patients. Results: Fifty-nine patients (47 TVR, 12 BOC) were studied. Median CD4 cell count was 457 (293-578)/mm3, and HIV viral load was

© The Author 2015. Published by Oxford University Press on behalf of the Infectious. Objective.To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum. Methods.HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated. Results.Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval,. 60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was

Simeprevir is an oral, once-daily, hepatitis C virus (HCV) NS3/4A protease inhibitor for the treatment of chronic HCV genotype 1 infection. Human immunodeficiency virus (HIV) coinfection accelerates progression of liver disease. This uncontrolled, open-label trial explored the safety and efficacy of simeprevir in patients with HCV genotype 1/HIV type 1 (HIV-1) coinfection.

Summary Background Two randomised, placebo-controlled trials—BENCHMRK-1 and BENCHMRK-2—investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibitor. We report final results of BENCHMRK-1 and BENCHMRK-2 combined at 3 years (the end of the double-blind phase) and 5 years (the end of the study). Methods Integrase-inhibitor-naive patients with HIV resistant to three classes of drug and who were failing antiretroviral therapy were enrolled. Patients were randomly assigned (2:1) to raltegravir 400 mg twice daily or placebo, both with optimised background treatment. Patients and investigators were masked to treatment allocation until week 156, after which all patients were offered open-label raltegravir until week 240. The primary endpoint was previously assessed at 16 weeks. We assessed long-term efficacy with endpoints of the proportion of patients with an HIV viral load of less than 50 copies per mL and less than 400 copies per mL, and mean change in CD4 cell count, at weeks 156 and 240. Findings 1012 patients were screened for inclusion. 462 were treated with raltegravir and 237 with placebo. At week 156, 51% in the raltegravir group versus 22% in the placebo group (non-completer classed as failure) had viral loads of less than 50 copies per mL, and 54% versus 23% had viral loads of less than 400 copies per mL. Mean CD4 cell count increase (analysed by an observed failure approach) was 164 cells per μL versus 63 cells per μL. After week 156, 251 patients (54%) from the raltegravir group and 47 (20%) from the placebo group entered the open-label raltergravir phase; 221 (47%) versus 44 (19%) completed the entire study. At week 240, viral load was less than 50 copies per mL in 193 (42%) of all patients initially assigned to raltegravir and less than 400 copies per mL in 210 (45%); mean CD4 cell count increased by 183 cells per μL. Virological failure occurred in 166 raltegravir recipients (36%) during the double-blind phase and in 17 of all patients (6%) during the open-label phase. The most common drug-related adverse events at 5 years in both groups were nausea, headache, and diarrhoea, and occurred in similar proportions in each group. Laboratory test results were similar in both treatment groups and showed little change after year 2. Interpretation Raltegravir has a favourable long-term efficacy and safety profile in integrase-inhibitor-naive patients with triple-class resistant HIV in whom antiretroviral therapy is failing. Raltegravir is an alternative for treatment-experienced patients, particularly those with few treatment options. Funding Merck Sharp & Dohme.

Objectives Dyslipidaemic effects of antiretrovirals (ARVs) may contribute to increased cardiovascular risk (CR) in HIV-1-infected patients. The ARTEN (atazanavir/ritonavir on a background of tenofovir and emtricitabine vs. nevirapine on the same background, in naive HIV-1-infected patients) study compared prospectively ritonavir-boosted atazanavir (ATZ/r) 300 mg/100 mg once daily (qd) with immediate release nevirapine (NVP) 200 mg twice daily or 400 mg qd, each combined with fixed-dose tenofovir 300 mg/emtricitabine 200 mg qd in 569 ARV-naive HIV-1-infected patients. Lipid profiles and CR from baseline to week 48 are reported. Methods Changes from baseline to week 48 in fasting plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), TC:HDL-c ratio, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total triglycerides (TG) were determined. The Framingham algorithm was used to estimate CR. Analysis was by intention-to-treat (ITT) with last observation carried forward (LOCF) for missing data. Results At week 48, NVP treatment resulted in significantly greater mean increases from baseline in TC (24.4 vs. 19.6 mg/dL; P=0.038), HDL-c (9.7 vs. 3.9 mg/dL; P < 0.0001), LDL-c (15.0 vs. 10.4 mg/dL; P=0.011) and ApoA1 (0.18 vs. 0.08 g/L; P < 0.0001) but not ApoB (0.02 vs. 0.02 g/L) compared with ATZ/r treatment. ATZ/r use was associated with higher mean TG increases (27.80 vs. 0.02 mg/dL; P=0.0001). Significantly greater mean decreases in TC:HDL-c and ApoB/ApoA ratios were observed with NVP vs. ATZ/r (P=0.0001 and P=0.008, respectively). Framingham CR scores were low and comparable between the arms, with only a slight mean increase from baseline to week 48 of 0.70 for NVP and 0.80 for ATZ/r [difference -0.069; 95% confidence interval (CI) -0.61 to 0.46; P=0.80]. Conclusions In ARV-naive patients with low CR at the outset, NVP showed a potentially less atherogenic lipid profile compared with ATZ/r.

BENCHMRK-1 and -2 are ongoing double-blind phase III studies of raltegravir in patients experiencing failure of antiretroviral therapy with triple-class drug-resistant human immunodeficiency virus infection. At week 96 (combined data), raltegravir (400 mg twice daily) plus optimized background therapy was generally well tolerated, with superior and durable antiretroviral and immunological efficacy, compared with optimized background therapy alone.

Gegenstand der Untersuchung:In Europa werden vermehrt Ausbrüche akuter HCV Infektionen unter HIV-positiven MSM beobachtet. Dabei fiel in der Region Nordrhein im Unterschied zu gemeldeten Fällen aus Gesamtdeutschland eine Häufung von HCV Genotyp 4 Infektionen auf. Um die Verwandtschaft[for full text, please go to the a.m. URL], 10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Hintergrund: EFV und LPV/r sind beides anerkannte first-line Bestandteile einer antiretroviralen Triple-Therapie zur Behandlung HIV positiver Patienten. Da direkte klinische Vergleiche beider Medikamente bzgl. ihrer Langzeitverträglichkeit selten sind, erfolgte diese retrospektive longitudinale[for full text, please go to the a.m. URL], 10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)