Joop E. Arends

Introduction It is unclear whether neurotoxicity due to the antiretroviral drug efavirenz (EFV) results in neurocognitive impairment in people living with HIV (PLWH). Previously, we found that discontinuing EFV was associated with improved processing speed and attention on neuropsychological assessment. In this imaging study, we investigate potential neural mechanisms underlying this cognitive improvement using a BOLD fMRI task assessing cortical and subcortical functioning. Methods Asymptomatic adult PLWH stable on emtricitabine/tenofovirdisoproxil/efavirenz were randomly (1:2) assigned to continue their regimen (n = 12) or to switch to emtricitabine/tenofovirdisoproxil/rilpivirine (n = 28). At baseline and after 12 weeks, both groups performed the Stop-Signal Anticipation Task, which tests reactive and proactive inhibition (indicative of subcortical and cortical functioning, respectively), involving executive functioning, working memory, and attention. Behavior and BOLD fMRI activation levels related to processing speed and attention Z-scores were assessed in 17 pre-defined brain regions. Results Both groups had comparable patient and clinical characteristics. Reactive inhibition behavioral responses improved for both groups on week 12, with other responses unchanged. Between-group activation did not differ significantly. For reactive inhibition, positive Pearson coefficients were observed for the change in BOLD fMRI activation levels and change in processing speed and attention Z-scores in all 17 regions in participants switched to emtricitabine/tenofovir disoproxil/rilpivirine, whereas in the control group, negative correlation coefficients were observed in 10/17 and 13/17 regions, respectively. No differential pattern was observed for proactive inhibition. Conclusion Potential neural mechanisms underlying cognitive improvement after discontinuing EFV in PLWH were found in subcortical functioning, with our findings suggesting that EFV’s effect on attention and processing speed is, at least partially, mediated by reactive inhibition. Trial Registration Clinicaltrials.gov identifier [NCT02308332].

Background: With regards to the global strategy towards eliminating viral hepatitis, reliable surveillance systems are essential to assess the national response for eliminating hepatitis C virus (HCV). Aim: We aimed to assess the completeness of the two national registries with data on acute HCV infection in people with HIV, and estimated the number of acute HCV infections among adults (aged ≥ 18 years) with HIV in the Netherlands. Methods: In this observational study, cases of HCV infection and reinfection among adults with a positive or unknown HIV-serostatus were identified from 2003 to 2016 in two national registries: the ATHENA cohort and the National Registry for Notifiable Diseases. For 2013–2016, cases were linked, and two-way capture–recapture analysis was carried out. Results: During 2013–2016, there were an estimated 282 (95% confidence interval (CI): 264–301) acute HCV infections among adults with HIV. The addition of cases with an unknown HIV-serostatus increased the matches (from n = 107 to n = 129), and subsequently increased the estimated total: 330 (95%CI: 309–351). Under-reporting was estimated at 14–20%. Conclusion: Under-reporting of acute HCV infection among people with HIV could partially be explained by an unknown HIV-serostatus, or by differences in HCV stage (acute or chronic) at first diagnosis. Surveillance data should ideally include both acute and chronic HCV infections, and enable to distinguish these as well as initial- and re-infections. National surveillance of acute HCV can be improved by increased notification of infections.

Background: Reliable surveillance systems are essential to assess the national response to eliminating hepatitis C virus (HCV), in the context of the global strategy towards eliminating viral hepatitis. Aim: We aimed to assess the completeness of the two national registries of acute HCV infection in people with HIV, and estimated the number of acute HCV infections among adults with HIV in the Netherlands. Methods: For 2003-2016, cases of HCV infection and reinfection among adults with a positive or unknown HIV-serostatus were identified in two national registries: the ATHENA cohort, and the National Registry for Notifiable Diseases. For 2013-2016, cases were linked, and two-way capture-recapture analysis was carried out. Results: During 2013-2016, there were an estimated 282 (95%CI: 264-301) acute HCV infections among adults with HIV. The addition of cases with an unknown HIV-serostatus increased the matches (from N=104 to N=129), and a subsequently increased the estimated total: 330 (95%CI: 309-351). Underreporting was estimated at 14-20%. Conclusion: In 2013-2016, up to 330 cases of acute HCV infection were estimated to have occurred among adults with HIV. National surveillance of acute HCV can be improved by increased notification of infections. Surveillance data should ideally include both acute and chronic HCV infections, and be able to distinguish between acute and chronic infections, and initial and reinfections. Classifications: The Netherlands; sexually transmitted infections; hepatitis C; HIV infection; Surveillance; epidemiology

Background & Aims: HIV/hepatitis B virus (HBV) coinfected subjects are thought to have faster progression to end‐stage liver disease (ESLD) than HBV mono‐infected subjects. We assessed whether this remains in the current cART‐era.Methods: Data from subjects with follow‐up completion post‐2003 were compared between HIV/HBV coinfected subjects in the Dutch HIV Monitoring database and HBV mono‐infected subjects from two centres. The primary outcomes of composite ESLD included portal hypertension, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation and liver‐related mortality. Outcomes were analysed using time‐dependent cause‐specific Cox regression models adjusted for follow‐up time and relevant covariates. Subset‐analyses were done in subjects with follow‐up pre‐2003.Results: In the 1336 co‐ vs 742 mono‐infected subjects, coinfected subjects had no increased probability for ESLD compared to mono‐infected subjects (cHR 0.7 (95% CI 0.4‐1.1), but had increased probabilities for all‐cause (cHR 7.4 [4.9‐11.1]) and liver‐related mortality (cHR 3.4 [1.6‐7.5]). In the current combined cohort, treatment with tenofovir or entecavir was inversely associated with ESLD, all‐cause and liver‐related mortality (cHR 0.4 [95% CI 0.3‐0.7], cHR 0.003 [0.001‐0.01]), cHR 0.007 [0.001‐0.05]). Other predictors for ESLD were older age, being of Sub‐Sahara African descent, increased alanine aminotransferase levels and hepatitis C virus coinfection. While the probability for all‐cause mortality was increased in coinfected subjects, this rate decreased compared to pre‐2003 (HR 40.2 (95% CI: 8.7‐186.2).Conclusions: HIV/HBV coinfected patients no longer seem to be at increased risk for progression to ESLD compared to HBV mono‐infected patients, likely due to widespread use of highly effective cART with dual HBV and HIV activity.

Elimination of the three blood-borne viruses—human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV)—as public health issues may be plausible in the near future. Spectacular advances have been made with the introduction of highly effective antiviral agents into clinical practice, and prevention strategies are available for all three infections. Effective disease control, laid out by WHO global strategies, is currently feasible for all three viruses. However, for worldwide elimination of these viruses, effective vaccines are required that are currently only available for HBV. In this review differences and parallels among HIV, HCV and HBV will be discussed with a focus on virologic and therapeutic issues, and prospects for the future of HBV will be presented.

Introduction Pegylated interferon-based therapy for hepatitis C virus (HCV) negatively impacts nutritional state and patient-reported outcomes (PROs) such as health-related quality of life (HRQL). Clinical trials with direct-acting antivirals (DAAs) report significant PRO improvement but real-world data are still scarce. Methods Prospective cohort study recruiting HCV patients treated with DAAs in 2015–2016. Data at baseline, end of treatment (EOT) and 12 weeks thereafter (FU₁₂) included: patient-reported medication adherence; SF-36; Karnofsky Performance Status; paid labour productivity; physical exercise level; nutritional state [by body mass index (BMI) and Jamar hand grip strength (HGS)] and Beliefs about Medicines Questionnaire. Potential factors predicting these PROs were evaluated with multiple regression analysis. Results A total of 68 patients were enrolled: 85% male, median age 57 years, 80% genotype 1, 40% cirrhotics, 46% haemophilia. Both cure rate and patient-reported adherence were 97%. SF-36 Physical Component Summary did not change (43.2 ± 11.9, 44.9 ± 10.3 and 44.7 ± 10.9 at baseline, EOT and FU₁₂, p = 0.71). In contrast, SF-36 mental component summary (MCS) decreased transiently during therapy (49.2 ± 11.9, 44.6 ± 10.3 and 49.9 ± 12.6 at baseline, EOT and FU₁₂, p < 0.01). Concomitant ribavirin-use was the only independent predictor of decreased SF-36 MCS. BMI (25.7 ± 4.5 and 25.6 ± 4.4 at baseline and EOT, p = 0.8) and Jamar HGS (39.7 ± 13.0, 37.4 ± 11.9 and 37.9 ± 13.8 at baseline, EOT and FU₁₂, p = 0.56) did not change. Conclusion Our study reveals concomitant ribavirin as the only independent predictor of transient decrease in SF-36 mental HRQL during DAA therapy. In contrast to interferon-based therapy, DAAs do not affect BMI or Jamar HGS.