An observational, prospective, multicenter study on the utilization and effectiveness of elbasvir-grazoprevir treatment association for chronic hepatitis C in France (ZEPHYR study).

Background and Aim: The efficacy and safety profiles of elbasvir-grazoprevir (EBR/GZR) has been established in more than 10 clinical trials. However, the characteristics of patients treated in routine clinical practice may differ. The present study was therefore designed to assess the real-life effectiveness of EBR/GZR therapy in the general population and among subgroups with a high hepatitis C virus (HCV) prevalence in France. Methods: The Zephyr study was designed as a French, multicentre, prospective, observational study on EBR/GZR use and effectiveness in current practice in chronic hepatitis C patients. These results are based on data regarding the adult patients who received at least one dose of EBR/GZR between December 2017 and June 2019 in 67 French hospitals and clinics. Results: Overall, 478 patients were included. The Full Analysis Set corresponded to the 467 patients who met all the inclusion criteria and none of the exclusion criteria. Gender was balanced and the mean age was 55.7 ± 13.3 years. The patients were mainly treatment-naive (89.5%) and infected with Genotype 1b (70.4%). Among the 75 patients with HCV Gt1a genotype, 56% had HCV RNA ≥ 800,000 IU/ml. F3-F4 fibrosis stage involved 24.2% of our population. Our subgroups were distributed among 110 migrants (23.6%), 58 (15.3%) using opioid agonist treatment, including people who inject drugs, 30 (6.8%) with chronic kidney disease Stages 3-5, 9 (1.9%) with an inherited blood disorder, and 4 (0.9%) coinfected with HIV. The remaining 269 (58.7%) were included in the general population subgroup. Overall, sustained virologic response 12 weeks after the end of treatment reached 98.0% and remained consistent among genotype, HCV RNA values, fibrosis stage, and the subgroup of interest. The rate of Alcohol Use Disorders Identification Test-Consumption​​​ and Life Habit questionnaire completion was high at each visit, with data suggesting alcohol consumption decrease and an improvement in quality of life. Conclusions: Using real-world evidence data on a French population representative of HCV patients, we confirmed the results obtained during EBR/GZR development program.

Necrotizing external otitis: analysis of relapse risk factors in 66 patients managed during a 12 year period.

BACKGROUND: Necrotizing external otitis (NEO) is a severe infection of the skull base that occurs generally in the elderly and/or in diabetic recipients. There are few data in the literature about the therapeutic management of this complex bone infection. OBJECTIVES: To analyse relapses after NEO treatment completion, and to describe the clinical features of NEO. METHODS: We performed a retrospective cohort study in the Lyon regional reference centre for the management of complex bone and joint infections. Consecutive cases of NEO from 1 January 2006 to 31 December 2018 were included. The primary outcome was the relapse of NEO. Variables were analysed using Cox regression survival analysis with adjusted hazard ratio (aHR) and Kaplan-Meier curve. RESULTS: Sixty-six patients were included. Median age was 75 (IQR 69-81) years and 46 (70%) patients were diabetic. Eleven patients (17%) had temporomandibular arthritis, 10 (15%) cranial nerve paralysis, 2 (3%) cerebral thrombophlebitis, and 2 (3%) contiguous abscess. Microbiological documentation was obtained in 56 patients and revealed Pseudomonas aeruginosa in 44/56 patients (79%). Nine (14%) cases had no microbiological documentation. Antibiotic therapy was dual for 63 (95%) patients. During a median follow-up of 27 (IQR 12-40) months, 16 out of 63 (25%) patients experienced a relapse. Fungal infection was significantly associated with relapse [aHR 4.1 (95% CI 1.1-15); P = 0.03]. CONCLUSIONS: NEO is a severe bone infection, mainly (but not exclusively) caused by P. aeruginosa, which occurs in elderly and diabetic recipients. Fungal infections at baseline significantly impact the outcome.

HCV cure: an appropriate moment to reduce cannabis use in people living with HIV? (ANRS CO13 HEPAVIH data).

BACKGROUND: Thanks to direct-acting antivirals, hepatitis C virus (HCV) infection can be cured, with similar rates in HCV-infected and HIV-HCV co-infected patients. HCV cure is likely to foster behavioral changes in psychoactive substance use, which is highly prevalent in people living with HIV (PLWH). Cannabis is one substance that is very commonly used by PLWH, sometimes for therapeutic purposes. We aimed to identify correlates of cannabis use reduction following HCV cure in HIV-HCV co-infected cannabis users and to characterize persons who reduced their use. METHODS: We used data collected on HCV-cured cannabis users in a cross-sectional survey nested in the ANRS CO13 HEPAVIH cohort of HIV-HCV co-infected patients, to perform logistic regression, with post-HCV cure cannabis reduction as the outcome, and socio-behavioral characteristics as potential correlates. We also characterized the study sample by comparing post-cure substance use behaviors between those who reduced their cannabis use and those who did not. RESULTS: Among 140 HIV-infected cannabis users, 50 and 5 had reduced and increased their use, respectively, while 85 had not changed their use since HCV cure. Cannabis use reduction was significantly associated with tobacco use reduction, a decrease in fatigue level, paying more attention to one's dietary habits since HCV cure, and pre-HCV cure alcohol abstinence (p = 0.063 for alcohol use reduction). CONCLUSIONS: Among PLWH using cannabis, post-HCV cure cannabis reduction was associated with tobacco use reduction, improved well-being, and adoption of healthy behaviors. The management of addictive behaviors should therefore be encouraged during HCV treatment.

Effect of Viral Replication and Liver Fibrosis on All-Cause Mortality in Human Immunodeficiency Virus-Hepatitis B Virus-Coinfected Individuals: A Retrospective Analysis of a 15-Year Longitudinal Cohort.

BACKGROUND: In individuals living with human immunodeficiency virus (HIV) and hepatitis B virus (HBV), widespread tenofovir (TDF)-containing antiretroviral therapy (ART) has led to substantial decreases in HBV-DNA and HIV-RNA detection. However, the links between viral replication, liver fibrosis, and mortality remain unclear. METHODS: A total of 300 individuals living with HIV-HBV and undergoing ART were prospectively followed. Virological and clinical data were obtained at baseline and every 6-12 months. We quantified the associations between HBV-DNA, HIV-RNA, and liver fibrosis with risk of all-cause mortality using a joint longitudinal survival model. Viral detection, viral loads, and time-averaged cumulative viral loads of HIV and HBV were modeled as 3 separate exposures. RESULTS: During a median of 10.5 years (interquartile range, 4.0-14.6), the proportion undergoing TDF-containing ART (baseline = 18.7%, end of follow-up = 79.1%) and with undetectable HBV-DNA (baseline = 36.7%, end of follow-up = 94.8%) substantially increased. 42 participants died (incidence rate = 1.30/100 person-years, 95% confidence interval [CI] = .96-1.76). The leading causes of death were non-AIDS/non-liver-related malignancies (28.6%), followed by liver-related (16.7%), AIDS-related (16.7%), and other (16.7%). All-cause mortality was associated with HBV-DNA viral load (adjusted hazards ratio [aHR] per log10 IU/mL = 1.41, 95% CI = 1.04-1.93, P = .03) or time-averaged cumulative HBV-DNA (aHR per log10 copy-years = 1.37, 95% CI = 1.03-1.83, P = .03), but not undetectable HBV-DNA. Advanced liver fibrosis at baseline was also associated with increased mortality rates (aHR = 2.35, 95% CI = 1.16-4.76, P = .02). No significant association between HIV-RNA replication and mortality was observed. CONCLUSIONS: Concurrent and historical HBV replication and liver fibrosis are important drivers of all-cause mortality in largely TDF-treated individuals living with HIV-HBV, despite one-fifth of deaths being liver-related. HBV-DNA and liver fibrosis remain important prognostic indicators for this patient population.

Persistent HBV replication and serological response during up to 15 years of tenofovir-based antiretroviral therapy in HIV/HBV-coinfected patients: a multicentre prospective cohort study.

OBJECTIVES: To determine the extent of hepatitis B virus (HBV) suppression and its association with seroclearance of hepatitis 'e' antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in HIV/HBV-coinfected patients undergoing long-term tenofovir-based antiretroviral therapy (ART). METHODS: We prospectively followed 165 HIV/HBV-coinfected patients undergoing tenofovir-based ART. Serum HBV-DNA viral loads and HBeAg and HBsAg status were obtained at tenofovir initiation and every 6-12 months. We calculated the proportion achieving virological response (VR, <60 IU/mL) during follow-up. We also calculated rates of HBeAg- and HBsAg-seroclearance, which were compared between those who achieved versus never achieved VR during follow-up using an Exact binomial test. RESULTS: During a median 8.1 years (IQR = 4.0-13.2) of tenofovir treatment, 152 (92.1%) patients were able to achieve VR and 13 (7.9%) never achieved VR (median HBV-DNA at the end of follow-up = 608 IU/mL, range = 67-52 400 000). The prevalence of individuals with detectable HBV-DNA (≥60 IU/mL) decreased during tenofovir treatment: 15.1% (n = 14/93) at 5 years, 3.2% (n = 2/62) at 10 years and, 3.2% (n = 1/31) at 15 years. 44/96 HBeAg-positive patients (6.15/100 person-years) had HBeAg-seroclearance and 13/165 patients overall (0.87/100 person-years) had HBsAg-seroclearance. No difference in HBeAg-seroclearance was observed between those who achieved versus never achieved VR (7.4 versus 3.7/100 person-years, P = 0.33), while HBsAg-seroclearance was only observed in those with VR (1.0 versus 0/100 person-years, P = 0.49; respectively). Individuals with VR also had a higher frequency of undetectable HIV-RNA during treatment (P < 0.001). CONCLUSIONS: During long-term tenofovir-based ART for HIV/HBV coinfection, persistent HBV viraemia is apparent, but becomes less frequent over time. HBsAg-seroclearance only occurred in those with full HBV and relatively high HIV suppression.

Profiles of liver fibrosis evolution during long-term tenofovir treatment in HIV-positive patients coinfected with hepatitis B.

BACKGROUND & AIMS: Data on liver fibrosis evolution and its involvement in liver-related morbidity are scarce in individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection during treatment. We identified profiles of liver fibrosis evolution in coinfected patients undergoing tenofovir (TDF). METHODS: We included 169 HIV-HBV-coinfected patients on TDF-based antiretroviral therapy. Virological and clinical data were obtained at TDF-initiation and every 6-12 months. From data on non-invasive liver fibrosis assessments collected yearly (FibroTest®), we established clusters of individuals with similar liver fibrosis evolution using group-based trajectory models. RESULTS: Four profiles of liver fibrosis evolution were established from a median follow-up of 7.6 years (IQR = 3.1-13.1): low fibrosis with no progression (29.6%, profile A), low fibrosis with progression (22.5%, profile B), moderate fibrosis with high fluctuation (39.6%, profile C), and cirrhosis with no regression (8.3%, profile D). When compared to profile A, baseline HBeAg-positive status was associated with profiles B (P = .007) and C (P = .004), older age with profiles C (P < .001) and D (P = .001), exposure to second-generation protease inhibitors with profile C (P = .004), and CD4+ <500/mm3 at the last visit with profiles C (P = .02) and D (P = .002). Incident liver-related events occurred in profiles other than A (B, n = 1/38; C, n = 6/67; D, n = 3/14) and all five cases of hepatocellular carcinoma occurred in profiles C (n = 2) and D (n = 3). CONCLUSIONS: TDF-treated HIV-HBV coinfected individuals do not seem to benefit from comparable levels of liver fibrosis regression as in HBV mono-infection. Liver-related morbidity occurs mainly in those with fluctuating or consistently high fibrosis levels.

Risk of severe clinical events after sustained virological response following direct-acting antiviral therapy in HIV and hepatitis C virus coinfected participants.

OBJECTIVES: Sustained virological response (SVR) decreases the risk of hepatitis C virus (HCV)-related events. Nevertheless, a substantial risk of events persists. We estimated incidences and identified factors associated with severe clinical events after SVR following treatment with a direct-acting antiviral (DAA) in HIV/HCV-coinfected patients. METHODS: Participants from the ANRS CO13 HEPAVIH were included if they reached SVR. Incidence rates of overall mortality, liver-related events, AIDS-defining events, ischaemic events and non-liver non-AIDS-defining cancers (NLNA) were estimated. Factors associated with the risk of those events were identified using Poisson models adjusted on age at SVR and sex. RESULTS: In all, 775 participants were included. Incidence rates (95% confidence interval) of liver-related events, overall mortality, AIDS-defining events, ischaemic events and NLNA cancers per 1000 person-years were 5.9 (3.3-10.3), 22.2 (16.8-29.5), 0.6 (0.1-4.5), 7.3 (4.4-12.2) and 13.7 (9.4-20.0), respectively. For all events, incidence rates were higher in cirrhotic than in non-cirrhotic participants. Cirrhosis, liver stiffness and CD4 count were associated with liver-related events. Factors associated with overall mortality were age, cirrhosis, liver stiffness and gamma-glutamyl transferase (GGT). For ischaemic events and NLNA cancers, associated factors were total cholesterol and CD4 count, respectively. CONCLUSIONS: After SVR following a DAA treatment, liver-related and AIDS-defining events were observed less frequently than NLNA cancers. Severity of liver disease was associated with the risk of liver-related events and of overall mortality but not with ischaemic events and NLNA cancers. Factors reflecting HIV infection were associated with NLNA cancers and liver-related events.

Subclinical and Clinical Outcomes in Patients Coinfected With HIV and Chronic Hepatitis B Virus From Clinical Outpatient Centers in France: Protocol for an Ambispective, Longitudinal Cohort Study.

BACKGROUND: Previous large-scale studies have examined the effect of chronic hepatitis B virus (HBV) infection on overall and cause-specific mortality in individuals with HIV. However, few studies have collected data on the subclinical indicators of HBV that lead to these severe outcomes in the coinfected population. OBJECTIVE: In this study, we aim to describe the procedures of a cohort study extension aimed at assessing HBV-DNA replication, serological markers of HBV (hepatitis B e antigen [HBeAg] and hepatitis B surface antigen), and liver fibrosis and how these subclinical outcomes relate to mortality in predominately tenofovir-treated, coinfected patients with HIV-HBV. We assessed the characteristics at cohort inclusion of those who participated in the cohort extension, as well as those who did not participate due to being lost to follow-up or death. METHODS: Patients with HIV and chronic HBV who completed follow-up in a prospective cohort study conducted in 4 outpatient centers (Paris and Lyon, France; 2002-2011) were invited to participate in a cross-sectional visit from November 2016 to March 2018, during which a comprehensive evaluation of HIV- and HBV-related disease was undertaken. Virological and clinical data since the previous study visit were retrospectively collected. RESULTS: Of the 308 individuals enrolled in the cohort, 147 (47.7%) participated in the cross-sectional study. At this visit, most participants were HBeAg negative (111/134, 82.8% with available data), had undetectable HBV DNA (124/132, 93.9% with available data), and were undergoing antiretroviral therapy containing tenofovir disoproxil fumarate or tenofovir alafenamide (114/147, 77.6%). There were no significant differences in characteristics at cohort inclusion between those who did and did not complete the cross-sectional visit, except for a lower proportion with an AIDS-defining illness (30/147, 20.5% vs 49/161, 30.4%, respectively; P=.04). Of the 161 nonparticipating individuals, 42 (26.1%) died, 41 (25.4%) were lost to follow-up and known to be alive, and 78 (48.4%) were lost to follow-up with unknown vital status. Most differences in characteristics at cohort inclusion were observed between deceased individuals and those participating in the cross-sectional visit or those lost to follow-up. With this extension, the median follow-up time of the overall cohort is presently 9.2 years (IQR 3.4-14.6). CONCLUSIONS: Extended follow-up of the French HIV-HBV cohort will provide important long-term data on the subclinical trajectory of HBV disease in the coinfected population. The biases due to the relatively high rate of those lost to follow-up need to be assessed in future studies of this cohort. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24731.

Recrudescence of a high parasitaemia, severe Plasmodium falciparum malaria episode, treated by artesunate monotherapy.

A patient presenting with severe malaria, with hyperparasitaemia, received 7-day artesunate monotherapy. A severe recrudescence was detected and attributed to hyperparasitaemia, monotherapy and a polyclonal infection without Kelch 13 gene mutation. A second treatment with artesunate, then quinine, followed by artemether-lumefantrine, was successful.

Coxiella burnetti prosthetic joint infection in an immunocompromised woman: iterative surgeries, prolonged ofloxacin-rifampin treatment and complex reconstruction were needed for the cure.

BACKGROUND: Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii, a strictly intracellular pathogen that can cause acute and chronic infection. Chronic Q fever can occur in immunocompetent as well as in immuno-compromised hosts, as a persistent localized infection. The main localizations are endocardial, vascular and, less frequently, osteoarticular. The most frequent osteoarticular form is spondyliscitis. Recommended treatment is combined doxycycline and hydroxychloroquine for 18 months, with cotrimoxazole as another option. Coxiella burnetti infection has been implicated in rare cases of prosthetic joint infection (PJI), and the medical and surgical management and outcome in such cases have been little reported. CASE PRESENTATION: We report an unusual case of chronic Q fever involving a hip arthroplasty in an immunocompromised woman treated with tumor necrosis factor (TNF)-α blockers for rheumatoid arthritis. Numerous surgical procedures (explantation, "second look", femoral resection and revision by megaprosthesis), modification of the immunosuppressant therapy and switch from doxycycline-hydroxychloroquine to prolonged ofloxacin-rifampin combination therapy were needed to achieve reconstruction and treat the PJI, with a follow-up of 7 years. CONCLUSIONS: Coxiella burnetti PJI is a complex infection that requires dedicated management in an experienced reference center. Combined use of ofloxacin-rifampin can be effective.

Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus.

BACKGROUND: An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. METHODS: HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. RESULTS: At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12), prior CVD (HR 8.48; 95% CI, 3.14-22.91), high total cholesterol (HR 1.43; 95% CI, 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08-0.63), statin use (HR 3.31; 95% CI, 1.31-8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35-7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18-0.96) was associated with coronary and/or cerebral events. CONCLUSIONS: HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.

Association of Hepatitis B Core-Related Antigen and Antihepatitis B Core Antibody With Liver Fibrosis Evolution in Human Immunodeficiency Virus-Hepatitis B Virus Coinfected Patients During Treatment With Tenofovir.

BACKGROUND: Quantitative hepatitis B core-related antigen (qHBcrAg) or antihepatitis B core antibody (qAnti-HBc) could be useful in monitoring liver fibrosis evolution during chronic hepatitis B virus (HBV) infection, yet it has not been assessed in human immunodeficiency virus (HIV)-HBV-coinfected patients undergoing treatment with tenofovir (TDF). METHODS: One hundred fifty-four HIV-HBV-infected patients initiating a TDF-containing antiretroviral regimen were prospectively followed. The qHBcrAg and qAnti-HBc and liver fibrosis assessment were collected every 6-12 months during TDF. Hazard ratios (HRs) assessing the association between qHBcrAg/qAnti-HBc and transitions from none/mild/significant fibrosis to advanced fibrosis/cirrhosis (progression) and from advanced fibrosis/cirrhosis to none/mild/significant fibrosis (regression) were estimated using a time-homogeneous Markov model. RESULTS: At baseline, advanced liver fibrosis/cirrhosis was observed in 40 (26%) patients. During a median follow-up of 48 months (interquartile range, 31-90), 38 transitions of progression (IR = 7/100 person-years) and 34 transitions of regression (IR = 6/100 person-years) were observed. Baseline levels of qHBcrAg and qAnti-HBc were not associated with liver fibrosis progression (adjusted-HR per log10 U/mL = 1.07, 95% confidence interval [CI] = 0.93-1.24; adjusted-HR per log10 Paul-Ehrlich-Institute [PEI] U/mL = 0.85, 95% CI = 0.70-1.04, respectively) or regression (adjusted-HR per log10 U/mL = 1.17, 95% CI = 0.95-1.46; adjusted-HR per log10 PEI U/mL = 0.97, 95% CI = 0.78-1.22, respectively) after adjusting for age, gender, duration of antiretroviral therapy, protease inhibitor-containing antiretroviral therapy, and CD4+/CD8+ ratio. Nevertheless, changes from the previous visit of qAnti-HBc levels were associated with liver fibrosis regression (adjusted-HR per log10 PEIU/mL change = 5.46, 95% CI = 1.56-19.16). CONCLUSIONS: Baseline qHBcrAg and qAnti-HBc levels are not associated with liver fibrosis evolution in TDF-treated HIV-HBV coinfected patients. The link between changes in qAnti-HBc levels during follow-up and liver fibrosis regression merits further study.

Correlation of serum hepatitis B core-related antigen with hepatitis B virus total intrahepatic DNA and covalently closed circular-DNA viral load in HIV-hepatitis B coinfection.

OBJECTIVE: To assess whether quantified hepatitis B core-related antigen (qHBcrAg) is a surrogate marker of intrahepatic replication in HIV and hepatitis B virus (HBV) coinfection. DESIGN: Cross-sectional study of 31 HIV-HBV-infected patients (total liver biopsies, n = 38) from a well defined cohort. METHODS: Spearman's rank correlation coefficients were calculated between qHBcrAg and intrahepatic markers of HBV replication [total intrahepatic-DNA, covalently closed circular (ccc) DNA, cccDNA : total intrahepatic-DNA ratio]. RESULTS: At biopsy, 22 (71.0%) patients were hepatitis B 'e' antigen (HBeAg)-positive, 22 (71.0%) had detectable plasma HBV-DNA, and 17 (54.8%) were treated with tenofovir. Median levels (interquartile range) of intrahepatic markers were as follows: HBV cccDNA (n = 34), 0.26 copies/cell (0.4-2.89); total intrahepatic-DNA (n = 38), 2.38 copies/cell (0.58-207.9), and cccDNA : total intrahepatic-DNA ratio (n = 34), 0.05 (interquartile range = 0.01-0.12). There was a significantly strong correlation between qHBcrAg and cccDNA in all patients (Rho = 0.65, P < 0.001), while a moderate correlation was observed between qHBcrAg and total intrahepatic-DNA (Rho = 0.57, P < 0.001) or cccDNA : total intrahepatic-DNA ratio (Rho = -0.45, P = 0.01). Similar findings were observed for HBeAg-positive patients and those with detectable HBV-DNA, with the exception of qHBcrAg and cccDNA or cccDNA : total intrahepatic-DNA ratio. In contrast, no significant correlation between qHBcrAg and any intrahepatic marker was observed in HBeAg-negative patients or those with undetectable HBV-DNA. No significant difference was observed in median qHBcrAg levels across liver fibrosis stages (P = 0.5). CONCLUSION: qHBcrAg is a potential surrogate marker of cccDNA in HIV-HBV coinfected patients, yet might be less useful with undetectable serum HBV-DNA or HBeAg-negative status. Whether qHBcrAg provides further clinical utility compared with other serological markers remains debatable.

Aspergillus endophthalmitis: Potential role for vitreous galactomannan testing?

Eye damage during invasive aspergillosis is rarely described and biological diagnosis remains challenging. Here we report the case of a heart transplant recipient with ocular aspergillosis complicating disseminated aspergillosis. Although voriconazole was rapidly given, a decrease in visual acuity of the right eye was consistent with endophthalmitis, resulting in an emergency vitrectomy. The diagnosis was rapidly confirmed: laboratory results showed the presence of Aspergillus fumigatus in a vitreous sample. A series of systemic antifungal medications (liposomal amphotericin B, caspofungin, and voriconazole), several liposomal amphotericin B ocular injections, and pars plana vitrectomy resulted in a limited positive clinical outcome. Interestingly although standard mycological follow-up procedures were negative, Aspergillus antigen testing gave an index of 5.92 on vitreous humour, thus a new intraocular injection of liposomal amphotericin B was performed and voriconazole reinitiated. Ten other vitreous samples from patients without fungal infections were also tested, all showing indexes below 0.25. Although larger studies are needed, this case illustrates that galactomannan testing of vitreous humour could be useful for the diagnosis of fungal endophthalmitis if these data are confirmed in other patients, in particular, if standard mycology is negative and PCR is not available.

Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM.

BACKGROUND: In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed. PATIENTS AND METHODS: In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection. RESULTS: In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%-99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients. CONCLUSIONS: Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM.

Kinetics of Hepatitis B Core-Related Antigen and Anti-Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus-Hepatitis B Coinfection.

BACKGROUND: The aim of the current study was to describe the kinetics of quantified hepatitis B core-related antigen (qHBcrAg) and quantified anti-hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF) treatment and assess their ability to predict hepatitis B e antigen (HBeAg) seroclearance in patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus. METHODS: Serum qHBcrAg, qAnti-HBc, and hepatitis B virus DNA were obtained at TDF initiation and every 6-12 months. The on-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HRs) assessing the association between markers and HBeAg seroclearance were calculated using proportional hazards regression, and the sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg seroclearance were assessed using time-dependent receiving operating characteristic curves. RESULTS: During a median of 4.6 years, the cumulative incidences of hepatitis B surface antigen and HBeAg seroclearance were 3.2% (n = 5 of 158) and 27.4% (n = 26 of 95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive patients (-0.051 and -0.011 log10 U/mL/mo during ≤18 and >18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg seroclearance (adjusted HR, 0.48/log10 U/mL [95% confidence interval, .33-.70] and unadjusted HR, 1.49/log10 Paul Ehrlich Institute units/mL [1.08-2.07], respectively). Cutoffs with the highest accuracy in predicting HBeAg seroclearance at 36 months were qHBcrAg <6.5 log10 U/mL at month 24 (Se, 1; Sp, 0.58) and baseline qAnti-HBc ≥4.1 log10 Paul Ehrlich Institute units/mL (Se, 0.42; Sp, 0.81). CONCLUSIONS: In coinfected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg seroclearance.