Search

Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART).We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059.Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; p0·0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause).After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients.Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica.

International audience; This paper deals with the vibroacoustic behavior of an electric window-lift gear motor for automotive vehicle which consists of a direct current (DC) motor and a worm gear. After describing the overall vibroacoustic behavior of this system and identifying the various excitation sources involved, this study focuses on the excitation sources associated to the contacts between brushes and commutator. To that end, a specific test bench is designed. It makes use of a modified gear motor for which various specific rotors are driven with an external brushless motor. It allows the discrimination of some excitation sources associated to the contact between brushes and commutator by removing them one after the other. The respective weight of friction, mechanical shocks, electrical current flow, and commutation arcs occurring jointly at the brush/commutator interface are dissociated and evaluated. The friction and the mechanical shocks between brushes and commutator blades increase the vibroacoustic response of the window-lift gear motor. The flowing of electrical current in brushes/commutator contacts tends to moderate the frictional component of excitation sources, while commutation arcs induce their rising, leading to a global additive contribution to the dynamic response.

Surfactant flooding is one of the effective technologies to enhance oil recovery of water flooded petroleum reservoirs. Several previous studies have demonstrated that the release of oil from a rock submitted to waterflood depends on the competition between displacing forces (viscous and buoyancy) and capillary forces. This competition is expressed by two dimensionless numbers, the Capillary number, defined as the ratio of viscous to capillary forces and the Bond number, defined as the ratio of gravity to capillary forces. At the core scale the evolution of the oil residual saturation as function of the capillary number is better known as the Capillary Desaturation Curve (CDC), which constitutes an important input parameter in EOR processes reservoir simulation. In this work we present a new experimental workflow to investigate the effect of rock structure on the CDC. This workflow combines core flood experiments and CT-scan imaging to accurately measure the mean residual oil saturation at different capillary number values as well as the local saturation distribution along the core plug. The CDC was measured on a set of water-wet sandstone with different permeability and degree of heterogeneity. The capillary number was varied by injecting a surfactant solution at different flow rates. Using this methodology, we first study the effect of core flood orientation (Horizontal injection and vertical downflow injection). The resulting local saturation curves show that in a horizontal configuration the oil migrates upwards in the sample inducing an oriented front strongly deviating from the piston like displacement, and very different from the one observed in the vertically placed sample. This behaviour is manly attributed to buoyancy forces that are no more negligible compared to capillary forces when surfactant is injected. This experiment shows that when measuring a CDC the capillary number needs to be corrected to take into account the buoyancy forces. In a second step we have investigated the effect of local heterogeneity of core plugs on the CDC with Clashach and Fontainebleau sandstones. Two samples of Clashash sandstone with equivalent mean properties were studied (mean permeability of 380 and 426 md and mean porosity of 13.4 % and 14.1% respectively). The resulting CDC curve exhibits almost two decades difference in the critical capillary number. This discrepancy is explained in terms of the local variation of the porosity that induces important differences in the local saturation profile.

International audience