Etravirine with 2 NRTIs: an effective switch option for ARV simplification and side effect management

Etravirine (ETV) has been approved for use in treatment-experienced patients based on results of the Duet clinical trials [1]. Less experience exists with ETV in earlier stages of treatment. ETV has a favorable genetic barrier, lipid profile, and little associated CNS toxicity. These characteristics make ETV attractive as a switch strategy for simplification and/or management of side effects. A retrospective chart review was conducted at a large urban HIV clinic in Toronto. All patients who were switched to ETV plus 2 nucleosides and whose viral load (VL) was <200 copies/ml at the time of switch were included. Maintenance of viral suppression, CD4 and lipid changes at 24 weeks and reason for switch to ETV are reported. Seventy-three patients (67 male) were identified. Mean age was 46±10 and mean duration of HIV infection was 11.7±7.4 years. Switches were from efavirenz=29, atazanavir=23, lopinavir=16, other=5. Duration of prior regimen was long; median 195 weeks. CNS and GI intolerance were the most common reasons for switches. At the time of analysis, 63 patients had reached week 24. Three patients had discontinued ETV prior to week 24, 3 LTF/U, 4 had <24 weeks follow-up. 92% (67/73) maintained VL suppression (ITT); failures were 6 patients who stopped/lost-to-follow-up prior to week 24. On treatment, CD4 increased and lipid decreased changes as seen below. All patients who switched due to CNS side effects had subjective improvement.Switch to ETV plus 2 nucleosides maintained viral suppression, improved lipid profiles and improved side effect profile in this selected group of patients. 48 week f/u will be presented

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] >= 50 copies/mL) and VL = 50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Recent Advances in Graph Partitioning

We survey recent trends in practical algorithms for balanced graph partitioning together with applications and future research directions

Framing the Real: Lefèbvre and NeoRealist Cinematic Space as Practice

In 1945 Roberto Rossellini's Neo-realist Rome, Open City set in motion an approach to cinema and its representation of real life – and by extension real spaces – that was to have international significance in film theory and practice. However, the re-use of the real spaces of the city, and elsewhere, as film sets in Neo-realist film offered (and offers) more than an influential aesthetic and set of cinematic theories. Through Neo-realism, it can be argued that we gain access to a cinematic relational and multidimensional space that is not made from built sets, but by filming the built environment. On the one hand, this space allows us to "notice" the contradictions around us in our cities and, by extension, the societies that have produced those cities, while on the other, allows us to see the spatial practices operative in the production and maintenance of those contradictions. In setting out a template for understanding the spatial practices of Neo-realism through the work of Henri Lefèbvre, this paper opens its films, and those produced today in its wake, to a spatio-political reading of contemporary relevance. We will suggest that the rupturing of divisions between real spaces and the spaces of film locations, as well the blurring of the difference between real life and performed actions for the camera that underlies much of the central importance of Neo-realism, echoes the arguments of Lefèbvre with regard the social production of space. In doing so, we will suggest that film potentially had, and still has, a vital role to play in a critique of contemporary capitalist spatial practices