Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients.

In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log10 IU/mL, respectively (P>.5 between groups). Median follow-up was 33.4 months (IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (-0.066 vs -0.027 PEIU/mL/month, P=.001) and qHBsAg (-0.049 vs -0.026 log10 IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.

Longitudinal evaluation of viral interactions in treated HIV-hepatitis B co-infected patients with additional hepatitis C and D virus.

Virological interactions of hepatitis B (HBV), hepatitis C (HCV) and hepatitis D (HDV) viruses in HIV-infected patients have been poorly characterized especially under treatment influences. Undetection rates of hepatitis viruses were longitudinally analyzed in a 3-year cohort of 308 HIV-HBV co-infected patients and compared using Generalized Estimating Equation models adjusted for age, HIV-RNA, CD4 cell-count and antiviral treatment. Chronic hepatitis co-infection in HIV-infected patients (age years, SD) was: 265 HBV (40.7, 8.2); 19 HBV-HCV (39.7, 4.1); 12 HBV-HDV (35.2, 9.9); 12 HBV-HCV-HDV (39.2, 5.2). At inclusion, treatment with lamivudine/tenofovir was not significantly different between co-infection groups. HBV suppression was significantly associated with HDV (aOR = 3.85, 95%CI 1.13-13.10, P = 0.03) and HCV tri-infection (aOR = 2.65, 95%CI 1.03-6.81, P = 0.04), but marginally associated with HIV-HBV-HCV-HDV (aOR = 2.32, 95%CI 0.94-5.74, P = 0.07). In quad-infection, lower HDV-undetectability (vs HIV-HBV-HDV, P = 0.2) and higher HCV-undetectability (vs HIV-HBV-HCV, P = 0.1) were demonstrated. The degree of HBV suppression varied between visits and co-infection groups [range of aOR during follow-up (vs HIV-HBV co-infection): HIV-HBV-HCV = 2.23-5.67, HIV-HBV-HDV = 1.53-15.17]. In treated co-infected patients, HDV expressed continuous suppression over HCV- and HBV-replications. Peaks and rebounds from undetectable hepatitis B, C and/or D viremia warrant closer follow-up in this patient population. HDV-replication was uncontrolled even with antiviral treatment.

Early control of HIV replication in primary HIV-1 infection treated with antiretroviral drugs and pegylated IFN alpha: results from the Primoferon A (ANRS 086) Study.

IFN alpha has both antiviral and immunostimulating properties. The ANRS086 Primoferon A Study evaluated in 12 patients with primary HIV infection the tolerance and efficacy of an early and transient administration of pegylated IFN alpha, in addition to highly active antiretroviral therapy. Tolerance was good, and this regimen allowed the early control of HIV replication and rapid decay of the viral reservoir. These results support the initiation of comparative studies with pegylated INF alpha in primary HIV infection.

Acute microbiologically negative hypoxic interstitial pneumonia on HAART: Immune Reconstitution Inflammatory Syndrome unmasking Pneumocystis jiroveci infection with an atypical presentation.

Highly active antiretroviral therapy for AIDS sometimes engenders inflammatory manifestations resulting from an inappropriate and unbalanced immune-system restoration, called Immune Reconstitution inflammatory Syndrome, which, in turn, can unmask a subclinical infection/pathology. Despite our patient's evident syndrome, the atypical clinical, microbiologic and radiologic feature of Pneumocystis pneumonia made its diagnosis difficult.

Determinants of the underreporting of alcohol consumption by HIV/HCV co-infected patients during face-to-face medical interviews: the role of the physician.

OBJECTIVES: The objective of this study was to assess to what extent HIV/HCV co-infected patients underreport alcohol use to their physician with respect to self-reports from self-administered questionnaires (SAQ) and identify correlates of alcohol underreporting during face-to-face medical interviews (FMI). DESIGN: ANRS-CO13-HEPAVIH is a French multi-center cohort of HIV/HCV co-infected patients. METHODS: Data were collected at enrolment using both SAQ and FMI while clinical data were retrieved from medical records. Alcohol consumption was assessed through SAQ and compared with FMI patient reports. Correlates of underreporting alcohol consumption during FMI with respect to SAQ were identified using logistic regression analysis. RESULTS: Among 544 patients, 37% were classified as alcohol abusers according to AUDIT-C in the SAQ. During FMI, 14% underreported alcohol consumption. The following correlates were independently associated with underreporting alcohol consumption in FMI: not receiving HIV treatment, being followed up by a hepatologist for HCV infection and reporting a history of injecting drug use. CONCLUSIONS: These results highlight the difficulties in alcohol consumption assessment which HCV specialists may face when suggesting to their HIV/HCV co-infected patients that they cease drinking completely. Patient awareness about the real need to reduce their alcohol use before starting HCV therapy may also contribute to underreporting. Innovative strategies for alcohol risk-reduction, including the promotion of controlled consumption and access to multidisciplinary teams, should be implemented for HIV/HCV co-infected patients in order to reduce barriers to HCV treatment.

Prevalence of immunity to hepatitis viruses A and B in a large cohort of HIV/HCV-coinfected patients, and factors associated with HAV and HBV vaccination.

UNLABELLED: Hepatitis A (HAV) and B (HBV) vaccination is strongly recommended for HIV-infected patients, especially those with hepatitis C coinfection. The aim of this study was to determine the prevalence of antibodies directed against HAV and HBV in a large cohort of HIV/HCV-coinfected patients, and to identify factors associated with HAV and HBV vaccination. PATIENTS AND METHODS: We studied 1175 HIV/HCV-coinfected patients enrolled in the ANRS CO13 HEPAVIH cohort, whose HAV and HBV serostatus was known. RESULTS: 1056 patients (89.9%) have been tested for anti-HBc IgG, anti-HBs, and HbsAg. Only 10.9% of patients had received HBV vaccination and 70% of the patients with no HBV immunity (231/265) had never received HBV vaccination. In multivariate analysis, male sex (OR 2.0. 95% CI 1.1-3.8; p=0.02), a higher level of school education (OR 2.5, 95% CI 1.3-4.5; p=0.003), a higher CD4 cell nadir (OR 1.05, 95% CI 1.009-1.103; p=0.018) and no cirrhosis (OR 2.7, 95% CI 1.2-6.4; p=0.02) were associated with HBV vaccination. Only 368 patients (31.3%) were tested for immunity to HAV. Despite a frequent lack of HAV immunity (48.3%), a low rate of HAV vaccination (6%) was observed. In multivariate analysis, a higher level of school education (OR 3.6, 95% CI 1.03-12.4; p=0.045) was the only factor associated with HAV vaccination. HAV screening rates and HAV and HBV vaccination rates were low in this population of HIV/HCV-coinfected patients. The benefits of routine HAV and HBV screening, vaccination and post-vaccination testing should be emphasized.

Histological scoring of fibrosis and activity in HIV-chronic hepatitis B related liver disease: performance of the METAVIR score assessed on virtual slides.

BACKGROUND: The METAVIR score, which is the most widely used score in France, was specifically elaborated and evaluated in chronic hepatitis C and has never been validated in HIV-hepatitis virus B (HBV) co-infected patients. AIMS: To validate the use of the METAVIR scoring system for activity and fibrosis on liver biopsies in co-infected HIV-HBV patients. METHODS: METAVIR scoring for activity and fibrosis was first conducted on both original and virtual slides by one pathologist for comparison. Then 55 biopsies turned into virtual slides were scored by three pathologists independently. RESULTS: The scoring comparison between virtual slides and glass slides showed an almost perfect agreement for fibrosis (weighted kappa (kappa(w)) 0.8) and a substantial agreement for activity (kappa(w) 0.68). The inter-observer agreement on virtual slides was moderate to almost perfect (kappa(w) 0.52 to 0.84) for fibrosis and was dependent on the pair of pathologists considered. The best agreement was obtained in scoring advanced fibrosis and cirrhosis versus significant fibrosis versus no or mild fibrosis (kappa(w) 0.70 to 0.84). The agreement for cirrhosis was rated moderate to substantial (kappa(w) 0.54 to 0.79). Agreement for activity was substantial (kappa(w) 0.66 to 0.8). CONCLUSIONS: This study validates the use of virtual slide technology to assess fibrosis and activity on liver biopsies. It also validates the use of the METAVIR score in co-infected HIV-HBV patients and illustrates the challenges in establishing the histological diagnosis of cirrhosis in the HIV-HBV context.