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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.

Dans les zones de savane subhumides d'Afrique de l'Ouest et du Centre, le modèle de production agricole inspiré par la révolution verte reste celui proposé aux agriculteurs et aux éleveurs. Il mobilise des intrants chimiques, des équipements et des races et variétés sélectionnées. Cette option a été confirmée après les émeutes de la faim de 2008, lorsque la plupart des États d'Afrique subsaharienne ont subventionné les engrais minéraux. Ce modèle de production n'est pas seulement proposé par les structures de développement ou le secteur privé, les agriculteurs sont aussi demandeurs d'un appui pour le mettre en place malgré ses limites et les risques encourus. Mais ces agriculteurs sont aussi détenteurs de savoir-faire reposant sur des processus écologiques qui permettraient un fonctionnement des agroécosystèmes plus efficace et plus durable. Mais les techniques mobilisant ces processus et savoir-faire sont souvent délaissés ou non applicables sur de grandes surfaces. Globalement l'intensification de la production par l'utilisation des intrants et d'équipements est bien mieux appréciée des producteurs que l'intensification écologique des systèmes de production. Bien que connus des structures de développement agricole ces modèle de production "agroécologiques" ont rarement été adoptés à grande échelle. Sans remettre en question l'intérêt des recherches sur l'Agroécologie et sur les l'IE des systèmes de production, on propose de mieux comprendre les choix des agriculteurs et des décideurs des pays du Sud afin de rapprocher leurs points de vue de ceux des chercheurs qui prônent ces nouveaux modèles de production agricole.

Dans les zones de savane subhumides d'Afrique de l'Ouest et du Centre, le modèle de production agricole inspiré par la révolution verte reste celui proposé aux agriculteurs et aux éleveurs. Il mobilise des intrants chimiques, des équipements et des races et variétés sélectionnées. Cette option a été confirmée après les émeutes de la faim de 2008, lorsque la plupart des États d'Afrique subsaharienne ont subventionné les engrais minéraux. Ce modèle de production n'est pas seulement proposé par les structures de développement ou le secteur privé, les agriculteurs sont aussi demandeurs d'un appui pour le mettre en place malgré ses limites et les risques encourus. Mais ces agriculteurs sont aussi détenteurs de savoir-faire reposant sur des processus écologiques qui permettraient un fonctionnement des agroécosystèmes plus efficace et plus durable. Mais les techniques mobilisant ces processus et savoir-faire sont souvent délaissés ou non applicables sur de grandes surfaces. Globalement l'intensification de la production par l'utilisation des intrants et d'équipements est bien mieux appréciée des producteurs que l'intensification écologique des systèmes de production. Bien que connus des structures de développement agricole ces modèle de production "agroécologiques" ont rarement été adoptés à grande échelle. Sans remettre en question l'intérêt des recherches sur l'Agroécologie et sur les l'intensification écologique (IE) des systèmes de production, on propose de mieux comprendre les choix des agriculteurs et des décideurs des pays du Sud afin de rapprocher leurs points de vue de ceux des chercheurs qui prônent ces nouveaux modèles de production agricole. (Texte intégral)

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.

IntroductionIn high‐income countries, ≥30% of HIV‐infected patients are ≥50 years (yrs) old (UNAIDS 2013). In two phases, three clinical trials (Studies 102 and 103) elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF; STB) had non‐inferior efficacy and favourable safety vs efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF; ATR) or ritonavir‐boosted atazanavir (ATV+RTV)+FTC/TDF (TVD) in HIV‐infected, treatment‐naïve subjects at Week 144. The efficacy and safety of STB in subjects < or ≥50 yrs is described.Materials and MethodsPost hoc analysis of efficacy, tolerability and safety in subjects < or ≥50 yrs at Week 144.ResultsSubjects ≥50 yrs in Study 102: STB: 14% (49/348), ATR: 16% (56/352); in Study 103: STB: 14% (48/353), ATV+RTV+TVD: 14% (48/355). Efficacy, safety and tolerability by age and study endpoint are shown in Table 1. Regardless of age, STB had robust efficacy at Week 144 with similar virologic outcomes vs ATR or ATV+RTV+TVD. Discontinuations (DC) due to AE on STB were similar to the comparators, most occurred by Week 48. Median changes in eGFR on STB were similar by age; DC with renal PRT was rare [STB: 4 (0.6%); ATV: 3 (0.8%); ATR: 0], 2 and 1 in ≥50 yrs old strata, respectively.ConclusionsSTB compared to ATR or ATV+RTV+TVD, is an efficacious, well‐tolerated and safe regimen for HIV‐1‐infected, treatment‐naïve subjects<or≥50 yrs of age.

IntroductionWe report the SVR12 final analysis of a phase 3 study of telaprevir in combination with peginterferon (P)/ribavirin (R) in HCV‐genotype 1, treatment‐naïve and ‐experienced patients with HCV/HIV co‐infection (INSIGHT).Materials and MethodsPatients receiving stable, suppressive HIV antiretroviral (ARV) therapy, containing atazanavir/ritonavir, efavirenz, darunavir/ritonavir, raltegravir, etravirine or rilpivirine, received telaprevir 750 mg q8h (1125 mg q8h if on efavirenz) plus P (180 µg once‐weekly) and R (800 mg/day) for 12 weeks, followed by an additional 12 weeks (non‐cirrhotic HCV treatment‐naïve and relapse patients with extended rapid viral response [eRVR]) or 36 weeks (all others) of PR alone. Analysis was performed when all patients had completed the follow‐up visit of 12 weeks after last planned dose.ResultsOne hundred sixty‐two patients were enrolled and treated (65 efavirenz, 59 atazanavir/ritonavir, 17 darunavir/ritonavir, 17 raltegravir, 4 etravirine). Mean age was 45 years, 78% were male, 92% were Caucasian; mean CD4 count was 687 cells/mm3. Sixty four patients (40%) were HCV treatment‐naïve and 98 (60%) were treatment experienced (29 relapsers, 18 partial responders and 51 null responders). 64% were subtype 1a. 30% had bridging fibrosis (17%) or cirrhosis (13%). 19% of patients discontinued telaprevir, including 9% due to an adverse event (AE), 8% reaching a virologic endpoint and 2% for other reasons (non compliance or not defined). Treatment responses are shown in Table 1. There were no HIV RNA breakthroughs. Most frequently reported (≥20% patients) AEs were pruritus 43%; fatigue 27%; rash 34%, anorectal events 30% and influenza‐like illness (25%). Anemia was reported in 15% of patients; grade ≥3 haemoglobin decrease occurred in 2.5% of patients. 6% of patients experienced serious AEs.ConclusionsIn this phase 3 study of HIV‐infected, HCV treatment‐naïve and ‐experienced patients, 49% achieved eRVR and 57% reached SVR12. In patients with an eRVR, SVR12 rates were >80%, irrespective of prior treatment history.

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‐Abnegative 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‐Abnegative 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 Spearmanρcorrelation 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,pbetween 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.

International audience ; Building bridges between environmental and political agendas is essential nowadays in face of the increasing human pressure on natural environments, including wetlands. Wetlands provide critical ecosystem services for humanity and can generate a considerable direct or indirect income to the local communities. To meet many of the sustainable development goals, we need to move our trajectory from the current environmental destructive development to a wiser wetland use. The current article contain a proposed agenda for the Pantanal aiming the improvement of public policy for conservation in the Pantanal, one of the largest, most diverse, and continuous inland wetland in the world. We suggest and discuss a list of 11 essential interfaces between science, policy, and development in region linked to the proposed agenda. We believe that a functional science network can booster the collaborative capability to generate creative ideas and solutions to address the big challenges faced by the Pantanal wetland.

International audience ; Building bridges between environmental and political agendas is essential nowadays in face of the increasing human pressure on natural environments, including wetlands. Wetlands provide critical ecosystem services for humanity and can generate a considerable direct or indirect income to the local communities. To meet many of the sustainable development goals, we need to move our trajectory from the current environmental destructive development to a wiser wetland use. The current article contain a proposed agenda for the Pantanal aiming the improvement of public policy for conservation in the Pantanal, one of the largest, most diverse, and continuous inland wetland in the world. We suggest and discuss a list of 11 essential interfaces between science, policy, and development in region linked to the proposed agenda. We believe that a functional science network can booster the collaborative capability to generate creative ideas and solutions to address the big challenges faced by the Pantanal wetland.

International audience ; Building bridges between environmental and political agendas is essential nowadays in face of the increasing human pressure on natural environments, including wetlands. Wetlands provide critical ecosystem services for humanity and can generate a considerable direct or indirect income to the local communities. To meet many of the sustainable development goals, we need to move our trajectory from the current environmental destructive development to a wiser wetland use. The current article contain a proposed agenda for the Pantanal aiming the improvement of public policy for conservation in the Pantanal, one of the largest, most diverse, and continuous inland wetland in the world. We suggest and discuss a list of 11 essential interfaces between science, policy, and development in region linked to the proposed agenda. We believe that a functional science network can booster the collaborative capability to generate creative ideas and solutions to address the big challenges faced by the Pantanal wetland.

International audience ; Building bridges between environmental and political agendas is essential nowadays in face of the increasing human pressure on natural environments, including wetlands. Wetlands provide critical ecosystem services for humanity and can generate a considerable direct or indirect income to the local communities. To meet many of the sustainable development goals, we need to move our trajectory from the current environmental destructive development to a wiser wetland use. The current article contain a proposed agenda for the Pantanal aiming the improvement of public policy for conservation in the Pantanal, one of the largest, most diverse, and continuous inland wetland in the world. We suggest and discuss a list of 11 essential interfaces between science, policy, and development in region linked to the proposed agenda. We believe that a functional science network can booster the collaborative capability to generate creative ideas and solutions to address the big challenges faced by the Pantanal wetland.

International audience ; Building bridges between environmental and political agendas is essential nowadays in face of the increasing human pressure on natural environments, including wetlands. Wetlands provide critical ecosystem services for humanity and can generate a considerable direct or indirect income to the local communities. To meet many of the sustainable development goals, we need to move our trajectory from the current environmental destructive development to a wiser wetland use. The current article contain a proposed agenda for the Pantanal aiming the improvement of public policy for conservation in the Pantanal, one of the largest, most diverse, and continuous inland wetland in the world. We suggest and discuss a list of 11 essential interfaces between science, policy, and development in region linked to the proposed agenda. We believe that a functional science network can booster the collaborative capability to generate creative ideas and solutions to address the big challenges faced by the Pantanal wetland.