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AbstractIntroduction: Long‐term tenofovir disoproxil fumarate (TDF) use has been associated with significant regression of liver fibrosis during hepatitis B virus (HBV) mono‐infection, yet little is known during HIV–HBV coinfection. The aim of this study was to evaluate the evolution of liver fibrosis and its determinants in TDF‐treated coinfected patients.Methods: In this prospective cohort study, 167 HIV–HBV‐infected patients initiating TDF‐containing antiretroviral therapy were included. Fibrosis was assessed using the FibroTest® at baseline and every six to twelve months. Risk factors for fibrosis progression (F0–F1–F2 to F3–F4) and regression (F3–F4 to F0–F1–F2) were evaluated.Results: At baseline, 134 (80.2%) patients had detectable HBV‐DNA (median = 4.93 log10 IU/mL, IQR = 2.94–7.15) and 104 (62.3%) had hepatitis B "e" antigen‐positive serology. Median follow‐up was sixty months (IQR = 36–93). In the 47 (28.1%) patients with F3–F4 baseline fibrosis, 7/47 (14.9%) regressed to F0–F1–F2 at last follow‐up visit. Fibrosis regression was significantly associated with higher CD4+ cell counts (P = 0.009) and lower fasting triglyceride levels (P = 0.007) at TDF‐initiation. In the 120 (71.9%) patients with F0–F1–F2‐baseline fibrosis, 20/120 (16.7%) progressed to F3–F4 at last follow‐up visit. Fibrosis progression was associated with male gender (P = 0.01), older age (P = 0.001), from low/moderate HBV‐endemic country (P = 0.007), lower nadir CD4+ cell count (P = 0.03), higher fasting glycaemia (P = 0.03) and anaemia (P = 0.004) at TDF‐initiation. Control of HBV replication at end of follow‐up was extensive (88.1%), while no HBV‐related factors emerged as predictors of progression/regression. Incidence of severe liver‐related events was low (n = 4, rate = 0.5/100 person‐years).Conclusions: Liver fibrosis levels are stable for most coinfected patients undergoing TDF, despite control of HBV replication. Nevertheless, a concerning amount of liver fibrosis progression did occur, which could be partly explained by metabolic abnormalities and past severe immunosuppression and requires further evaluation.

IntroductionEtravirine (ETR), a non‐nucleoside reverse transcriptase inhibitor available in France since 2006, is indicated for the treatment of HIV‐1 infection in combination with a ritonavir boosted protease inhibitor (PI) in antiretroviral treatment‐experienced adult patients. To assess its impact in routine clinical care, our objective was to compare hospitalization rates in highly pre‐treated failing HIV‐1 infected individuals between 2005 and 2011 depending on whether or not they received ETR+PI.MethodsFrom the French Hospital Database on HIV (ANRS CO4), we selected highly pre‐treated individuals (prior exposure to at least 2NRTI, 2PI and 1 NNRTI) with a viral load (VL)>50 copies/mL initiating a new regimen between 2005 and 2011. Hospitalization rates were calculated for each calendar month and depending on whether patients never received ETR+PI at any time or during months before initiating ETR+PI (no ETR+PI) or during months after initiating ETR+PI (ETR+PI), using an intention to continue treatment approach. Poisson regression models were used to compare incidence between the two groups, after adjustment for potential confounders (age, transmission group, origin, AIDS, PCP prophylaxis, viral load, CD4, nb of previous ARV).ResultsOverall 3884 patients fulfilled inclusion criteria. Among them 838 (21.6%) received ETR+PI at least once. Among all enrolled patients, 35.8% had CD4 <200/mm3, 17.5% had VL >100,000 copies/ml, 42.8% had had an AIDS event and 47.8% had received more than 10 different antiretroviral drugs. There were 2484 hospitalizations in 808 individuals over 13,986 patient‐years. The hospitalization rates for 1000 P‐Y were 169.0 for the ETR+PI group and 179.3 for the no ETR+PI group. After adjustment, the corresponding figures were 144.8 for 1000 P‐Y and 192.7 for 1000 P‐Y respectively, with a relative risk estimated as 0.75 (95% CI 0.67–0.84).ConclusionsAccess to ETR+PI between 2005 and 2011 was associated with a 25% reduction in the hospitalization rate among highly pre‐treated failing HIV‐1 infected individuals.

IntroductionThe efficacy of protease inhibitor monotherapy has been analyzed with different endpoints: initial HIV‐1 RNA rebound, long‐term HIV‐1 RNA suppression after re‐intensification, treatment‐emergent drug resistance, neurocognitive testing and HIV‐1 RNA in the cerebrospinal fluid (CSF).MethodsA PUBMED search identified nine randomised trials of PI monotherapy versus triple therapy in patients with HIV RNA<50 copies/mL at baseline. Results from the recently completed PROTEA trial were also included. The percentage of patients with HIV RNA suppression <50 copies/mL was analyzed using switch equals failure and intensification included endpoints (ITT). The number of patients with new drug resistance mutations, HIV RNA in the CSF or change in neurocognitive function was analyzed by treatment arm.ResultsFour trials evaluated darunavir/r monotherapy (n=785: MONET, MONOI, MONARCH, PROTEA), five evaluated lopinavir/r monotherapy (n=592: OK‐04, KalMo, KALESOLO, KRETA, MOST) and one evaluated both (MRC PIVOT, n=587). HIV‐1 RNA suppression rates tended to be lower on PI monotherapy than triple therapy in "switch equals failure" analysis (76% vs 82%), but not when the outcome of intensification was included (87% vs 85%). There were small numbers of patients taking PI monotherapy with detectable HIV‐1 RNA in the CSF, in three trials: PROTEA (n=2), MONOI (n=2) and MOST (n=5), but only two cases of CSF viral escape (MONOI). In two trials, there was no difference in neurocognitive test results between PI monotherapy and triple therapy, based on z‐scores from five domains (in PROTEA, mean change in NPZ‐5 score=0.0 for DRV/r monotherapy vs −0.10 for triple therapy); similar results were observed in the MRC PIVOT trial. The risk of treatment emergent NRTI or PI resistance (Table 1) was 11/973 (1.1%) for patients on PI monotherapy, versus 7/991 (0.7%) for patients on triple therapy.ConclusionsIn 10 randomised trials of 1964 patients with HIV‐1 RNA suppression at baseline, PI monotherapy showed a higher risk of HIV RNA elevations, and small numbers with HIV RNA detectable in CSF and concomitantly in the plasma. However there was no increased risk of treatment‐emergent drug resistance, neurocognitive endpoints were not different between the arms and HIV‐1 RNA suppression rates after intensification were similar between PI monotherapy and triple therapy.

IntroductionIn previous studies, protease inhibitor (PI) monotherapy has shown trends for higher low‐level elevations in HIV‐1 RNA compared to triple therapy, but no increase in the risk of drug resistance.MethodsA total of 273 patients with HIV‐1 RNA <50 copies/mL for over 24 weeks on current antiretrovirals switched to DRV/r (darunavir/ritonavir) 800/100 mg once‐daily, either as monotherapy (n=137) or with 2NRTIs (nucleoside reverse‐transcriptase inhibitors) (n=136), after a 4 week run‐in phase with DRV/r + 2NRTI. Treatment failure was defined as HIV‐1 RNA levels above 50 copies/mL (FDA Snapshot method) by Week 48, or switches off study treatment. Patients with elevations in HIV‐1 RNA on DRV/r monotherapy could be re‐intensified with NRTIs. The trial had 80% power to show non‐inferiority for the monotherapy arm (delta = − 12%).ResultsPatients were 83% male and 87% Caucasian, with mean age 42 years; 10% were HCV antibody positive. In the DRV/r monotherapy arm, there were more patients with nadir CD4 count below 200 cells/µL (30% versus 22%). In the primary efficacy analysis, HIV‐1 RNA <50 copies/mL by Week 48 (intent‐to‐treat (ITT)) was 118/137 (86.1%) in the DRV/r monotherapy arm versus 129/136 (94.9%) in the triple therapy arm; DRV/r monotherapy did not show non‐inferiority versus triple therapy in the primary analysis (difference=− 8.7%, 95% CI −15.5 to −1.8%). In the multivariate analysis, the main predictor of treatment failure was nadir CD4 count. For patients with nadir CD4 counts <200 cells/µL, HIV‐1 RNA suppression rates at Week 48 were 27/41 (66%) in the DRV/r monotherapy arm and 29/30 (97%) in the triple therapy arm; for patients with CD4 nadir at least 200 cells/µL, HIV‐1 RNA suppression rates were 91/96 (95%) in the DRV/r monotherapy arm and 100/106 (94%) in the triple therapy arm. In the overall population, by a switch included analysis, efficacy was 92.0% versus 96.3%, showing non‐inferiority (difference=− 4.3%, 95% CI=−9.7 to +1.2%). No treatment‐emergent primary PI mutations were detected in three patients with sustained elevations in HIV‐1 RNA at least 400 copies/mL (two on PI monotherapy, one on triple therapy). CD4 counts remained stable during the trial in both arms.ConclusionsIn this study for patients with HIV‐1 RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple antiretroviral therapy at Week 48 in the primary switch equals failure analysis (86% versus 95%). However, this lower efficacy was seen mainly in patients with CD4 nadir levels below 200 cells/µL. There was no development of PI resistance.

ObjectivesData on the extent of drug use and associated HIV, hepatitis C and hepatitis B infection in West Africa are lacking. The objectives of ANRS12244 UDSEN study were to estimate the size of the heroin and/or cocaine drug user (DU) population living in the Dakar area (Senegal), and assess the prevalence and risk factors of HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV), including behavioural determinants in this population, in order to set up an integrated prevention and treatment programme for DUs.Design and methodsA capture‐recapture method was applied for population size estimation, whereas the respondent‐driven sampling (RDS) method was used to recruit a sample of DUs living in the Dakar area and determine HIV, HBV and HCV prevalence. Behavioural data were gathered during face‐to‐face interviews, and blood samples were collected on dried blood spots for analysis in a central laboratory. Data analysis was performed using the RDS analysis tool, and risk factors were determined by logistic regression. Access to laboratory results was organized for the participants.ResultsThe size of the DU population in the Dakar area was estimated to reach 1324 (95% confidence interval (95% CI: 1281–1367)). Based on the 506 DUs included in the study, the HIV, HCV and HBV prevalence were 5.2% (95% CI: 3.8–6.3), 23.3% (95% CI: 21.2–25.2) and 7.9% (95% CI: 5.2–11.1), respectively. In people who inject drugs (PWID), prevalence levels increased to 9.4% for HIV and 38.9% for HCV (p=0.001 when compared to those who never injected). Women were more at risk of being HIV infected (prevalence: 13.04% versus 2.97% in males, p=0.001). Being PWID was a risk factor for HCV and HIV infection (odds ratio, OR: 2.7, 95% CI: 1.7–4.3, and OR: 4.3, 95% CI: 1.7–10.7, respectively), whereas older age and female sex were additional risk factors for HIV infection (10% increase per year of age, p=0.03 and OR: 4.9, 95% CI: 1.6–156, respectively). No specific determinant was associated with the risk of HBV infection.ConclusionsHigh HIV and HCV prevalence were estimated in this population of DUs (including non‐injectors) living in the Dakar area, Senegal, whereas HBV prevalence was close to that of the global Senegalese population, reflecting a risk of infection independent of drug use. Women seem to be highly vulnerable and deserve targeted interventions for decreasing exposure to HIV, while behavioural risk factors for HIV and HCV include the use of unsafe injections, reflecting the urgent need for developing harm reduction interventions and access to opioid substitution therapy services.

AbstractIntroduction: The diagnostic procedure for chronic hepatitis C infection (CHC) usually combines anti‐HCV antibody (HCV‐Ab) and HCV‐RNA measurement. Quantifying HCV core antigen (cAg) as a one‐step procedure could shorten the diagnostic process. We aimed to assess the performance of cAg quantification in diagnosing CHC and how it is influenced by concomitant HIV or HBV infections.Methods: The cAg was quantified by an automated assay (Abbott Diagnostics) in 465 HCV‐Ab negative serum samples and 544 HCV‐RNA positive serum samples (n = 1009) collected in patients from the Pasteur Center in Cameroon, some of whom were infected by HBV or HIV. Its performance was evaluated in comparison to the gold standard (ELISA or PCR) by estimating its sensitivity (Se) and specificity (Sp), and by comparing the area under ROC (AUROC) curves in each patient population: HCV mono‐infected, HCV‐HBV and HIV‐HCV co‐infected.Results: Among the 465 HCV‐Ab negative patients, 51 and 79 were HIV‐ and HBV‐infected, respectively, whereas among the 544 patients with CHC, 27 and 28 were HIV‐ and HBV‐infected, respectively. The Spearman ρ correlation coefficient between cAg and HCV‐RNA was 0.75 (p < 0.00001). The assay had a sensitivity of 95.7% (95% CI: 93.2–97.5) and a specificity of 99.7% (95% CI: 98.1–10) in diagnosing CHC, corresponding to an AUROC of 0.99 (95% CI: 0.98–1.0). Being HIV‐ or HBV‐infected did not impact the performance of cAg (Se = 96.4%, Sp = 96.2% and AUROC = 0.98 (95% CI: 0.95–1.0) in the HBV group, Se = 100%, Sp = 88.2% and AUROC = 0.99 (95% CI: 0.97–1.0) in the HIV group, p between AUROC = 0.69).Conclusions: The cAg quantification displayed a high specificity and sensitivity for the diagnosis of CHC in Cameroon, and its performance was not significantly modified by a concomitant HIV or HBV infection. In the context of CHC elimination on a global scale, using cAg quantification as a screening tool to directly identify CHC could be a reliable tool in a "test and treat" strategy.