kill' strategy, for future trials significant enhancement of both 'kick' and 'kill' agents will be required. Research in context panel Evidence before this study This randomised clinical trial was designed to test the concept of 'kick and kill' as a strategy to achieve a cure for HIV infection. Prior to this study, there was evidence from in vitro and single arm clinical studies that the histone deacetylase inhibitor (HDACi) class of drugs could induce viral transcription from latently infected cells, potentially creating a target for the immune system. In conjunction with this 'kick' to the latent HIV reservoir there was evidence that T cell immunitywhich determines HIV disease progression-could be enhanced through vaccination-induced responses, providing the 'kill'. Although the strategy of 'kick and kill' looked promising, there had been no powered RCTs to test it. Added value of the study RIVER tested 'kick and kill' using the HDACi vorinostat as the 'kick' combined with a vaccine strategy targeting conserved regions of the HIV genome. The vaccine aimed to produce T cells to kill latently-infected cells in which viral transcription had been induced by the HDACi. RIVER showed that the intervention was safe, with outstanding adherence to the complex trial protocol by the participants. However, even though there was evidence for both increased histone acetylation and potent vaccine-induced T-cell responses, the intervention did not confer any additional benefit on any measures of the HIV reservoir compared with antiretroviral therapy alone. Implications of all the available evidence. RIVER was the first RCT in treated recent HIV infection, and was not able to show any impact of 'kick and kill' on the primary outcome measure, or any marker of the HIV reservoir size. This is consistent with other studies which had tested HDACi alone. We did not, however, stop antiretroviral therapy in the RIVER trial participants, and future studies may include a treatment interruption as a further measure of impact. Whilst the RIVER trial suggests that this specific 'kick and kill' approach may not be an effective approach towards achieving HIV cure, the overall principle can not yet be dismissed, as more potent future interventions may have a greater impact.

No abstract

Twenty-five horses undergoing arthroscopic surgery were studied to develop a scheme for assessing pain in horses while investigating the effects of phenylbutazone (PBZ) analgesia. Fifteen of the 25 horses received PBZ 4 mg/kg intravenously (IV) before surgery and 2 mg/kg (IV) every 12 hours thereafter until 60 hours; the remaining 10 (placebo group) were given a corresponding volume of saline. In both groups, venous blood samples were collected for catecholamine, beta-endorphin, and cortisol assays before premedication and up to 72 hours after surgery. Postoperative pain was evaluated by measuring predefined behavioral and physiological variables. A total postoperative pain severity index (TPPSI) was calculated using all variables. There were no differences between PBZ and placebo groups in plasma beta-endorphin or catecholamine concentrations, but the TPPSI was higher in the placebo group than in the PBZ group, suggesting that perioperative treatment with PBZ has some analgesic benefit. This study shows the difficulties associated with pain assessment in horses.