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Persistence of HIV through integration into host DNA in CD4(+) T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8(+) T cells are triggered to kill infected CD4(+) T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has been reported only in individuals with "beneficial'' HLA alleles that are associated with superior HIV control. Through interrogation of the pre-integration immunopeptidome, we obtain proof of early presentation of a virion-derived HLA-A*02:01-restricted epitope, FLGKIWPSH (FH9), located in Gag Spacer Peptide 2 (SP2). FH9-specific CD8(+) T cell responses are detectable in individuals with primary HIV infection and eliminate HIV-infected CD4(+) T cells prior to virus production in vitro. Our data show that non-beneficial HLA class I alleles can elicit an effective antiviral response through early presentation of HIV virion-derived epitopes and also demonstrate the importance of SP2 as an immune target.

Persistence of HIV through integration into host DNA in CD4

Background: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing—termed kick and kill regimens—have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to determine the effect of ART-only versus ART plus kick and kill on markers of the HIV reservoir. Methods: This phase 2, open-label, multicentre, randomised, controlled trial was undertaken at six clinical sites in the UK. Patients aged 18–60 years who were confirmed as HIV-positive within a maximum of the past 6 months and started ART within 1 month from confirmed diagnosis were randomly assigned by a computer generated randomisation list to receive ART-only (control) or ART plus the histone deacetylase inhibitor vorinostat (the kick) and replication-deficient viral vector T-cell inducing vaccines encoding conserved HIV sequences ChAdV63. HIVconsv-prime and MVA.HIVconsv-boost (the kill; ART + V + V; intervention). The primary endpoint was total HIV DNA isolated from peripheral blood CD4+ T-cells at weeks 16 and 18 after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02336074. Findings: Between June 14, 2015 and Jul 11, 2017, 60 men with HIV were randomly assigned to receive either an ART-only (n=30) or an ART + V + V (n=30) regimen; all 60 participants completed the study, with no loss-to-follow-up. Mean total HIV DNA at weeks 16 and 18 after randomisation was 3·02 log10 copies HIV DNA per 106 CD4+ T-cells in the ART-only group versus 3·06 log10 copies HIV DNA per 106 CD4+ T-cells in ART + V + V group, with no statistically significant difference between the two groups (mean difference of 0·04 log10 copies HIV DNA per 106 CD4+ T-cells [95% CI −0·03 to 0·11; p=0·26]). There were no intervention-related serious adverse events. Interpretation: This kick and kill approach conferred no significant benefit compared with ART alone on measures of the HIV reservoir. Although this does not disprove the efficacy kick and kill strategy, for future trials enhancement of both kick and kill agents will be required.

We investigated whether a treatment switch from Atripla® (tenofovir, emtricitabine, and efavirenz) to DRV/r monotherapy may improve neuropsychological performance, health-related quality of life, and sleep function. Virologically suppressed subjects and asymptomatic on Atripla for ≥6 months were randomized 1:1 to continue Atripla or switch to boosted darunavir (DRV/r) 800/100 mg once daily for 48 weeks. Neurocognitive tests, the International HIV Dementia Scale (IHDS), Medical Outcomes Study HIV Health Survey (MOS-HIV), EQ-5D-3L, and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline and at week 48. Sleep function was evaluated at week 48. Twenty-six patients on DRV/r and 31 on Atripla completed the 48-week study. No significant difference in the change in scores from week 0 to week 48 between the two arms was observed in neurocognitive outcomes, IHDS, health outcomes (EQ-5D-3L and QOL), and HADS score. By contrast, the HADS score and sleep quality were both significantly...

The purpose of the research was to study changes in handwriting legibility among kindergarten, first- and second-grade students in response to the Size Matters curricular-based handwriting program. A two-group pre–post-test design was implemented at two public schools with half of the classrooms assigned to receive the Size Matters program and the other continuing to receive standard instruction. All participants completed two standardized handwriting measures at pre-test and after 40 instructional sessions were completed with the classes receiving the handwriting program. Results identified significant changes in legibility in the handwriting intervention group for all three grades when compared with the standard instruction group. The results of this study support the use of a curricular-embedded handwriting program and provide the foundation for future research examining the impact of handwriting legibility on learning outcomes.

We determined whether a widely used assessment of visual–motor skills, the Beery–Buktenica Developmental Test of Visual–Motor Integration (VMI), is appropriate for use as an outcome measure for handwriting interventions. A two-group pretest–posttest design was used with 207 kindergarten, first-grade, and second-grade students. Two well-established handwriting measures and the VMI were administered pre- and postintervention. The intervention group participated in the Size Matters Handwriting Program for 40 sessions, and the control group received standard instruction. Paired and independent-samples t tests were used to analyze group differences. The intervention group demonstrated significant improvements on the handwriting measures, with change scores having mostly large effect sizes. We found no significant difference in change scores on the VMI, t(202) = 1.19, p = .23. Results of this study suggest that the VMI may not detect changes in handwriting related to occupational therapy intervention.

The 802.11p protocol, also known as wireless access for the vehicular environment (WAVE), has recently gained momentum in the area of research and development. The WAVE protocol provides enhancements to the physical (PHY) and medium access control (MAC) layers of the existing 802.11 wireless standards. These enhancements are required to support the intelligent transportation systems (ITS) initiatives of the US Department of Transportation regarding vehicle-to-vehicle, vehicle-to-infrastructure, and infrastructure-to-vehicle communication. Many research groups have contributed to the development of the protocol. Many of the same individuals have worked to extend the ns-2 network simulator to correctly simulate wireless mobile networking, specifically vehicle adhoc networks (VANETs). The objective of this research project is to measure the performance of the WAVE protocol at the MAC layer, using the ns-2 simulator. Specifically, the simulations measure aggregate throughput, average delay, and packet loss metrics.