Therapeutic DNA vaccination of vertically HIV-infected children: Report of the first pediatric randomised trial (PEDVAC)

Subjects: Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm³. Intervention: Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results: Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions: The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration: clinicaltrialsregister.eu 2007-002359-18; 2007-002359-18/I

Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors

<p>Abstract</p> <p>Background</p> <p>Kidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI).</p> <p>Methods</p> <p>Serum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI.</p> <p>Results</p> <p>Forty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m²at baseline to 128.9 after 2 years (<it>p </it>= 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (<it>p </it>= 0.0003) and in TDF+PI group (<it>p </it>= 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI.</p> <p>Conclusions</p> <p>Renal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.</p

What evidence exists on the links between natural climate solutions and climate change mitigation outcomes in subtropical and tropical terrestrial regions? A systematic map protocol

Background Natural climate solutions (NCS)—actions to conserve, restore, and modify natural and modified ecosystems to increase carbon storage or avoid greenhouse gas (GHG) emissions—are increasingly regarded as important pathways for climate change mitigation, while contributing to our global conservation efforts, overall planetary resilience, and sustainable development goals. Recently, projections posit that terrestrial-based NCS can potentially capture or avoid the emission of at least 11 Gt (gigatons) of carbon dioxide equivalent a year, or roughly encompassing one third of the emissions reductions needed to meet the Paris Climate Agreement goals by 2030. NCS interventions also purport to provide co-benefits such as improved productivity and livelihoods from sustainable natural resource management, protection of locally and culturally important natural areas, and downstream climate adaptation benefits. Attention on implementing NCS to address climate change across global and national agendas has grown—however, clear understanding of which types of NCS interventions have undergone substantial study versus those that require additional evidence is still lacking. This study aims to conduct a systematic map to collate and describe the current state, distribution, and methods used for evidence on the links between NCS interventions and climate change mitigation outcomes within tropical and sub-tropical terrestrial ecosystems. Results of this study can be used to inform program and policy design and highlight critical knowledge gaps where future evaluation, research, and syntheses are needed. Methods To develop this systematic map, we will search two bibliographic databases (including 11 indices) and 67 organization websites, backward citation chase from 39 existing evidence syntheses, and solicit information from key informants. All searches will be conducted in English and encompass subtropical and tropical terrestrial ecosystems (forests, grasslands, mangroves, agricultural areas). Search results will be screened at title and abstract, and full text levels, recording both the number of excluded articles and reasons for exclusion. Key meta-data from included articles will be coded and reported in a narrative review that will summarize trends in the evidence base, assess gaps in knowledge, and provide insights for policy, practice, and research. The data from this systematic map will be made open access

The Irredeemable Debt: On the English Translation of Lacan's First Two Public Seminars

This is an Accepted Manuscript of an article published by Edinburgh University Press in Psychoanalysis and History . The Version of Record is available online at: https://www.euppublishing.com/doi/10.3366/pah.2017.0214Drawing on archival sources and personal recollections, this essay reconstructs the troubled history of the first robust attempt at making the works of the French psychoanalyst Jacques Lacan newly available to an anglophone readership, after his death in 1981. It details how the project was initiated by John Forrester as part of a large-scale initiative to generate translations of both Lacan’s own texts and seminars, and various books written in the Lacanian tradition. If, almost seven years after it was conceived, Forrester’s project only resulted in the publication of English translations of Lacan’s first two public seminars, the essay demonstrates that this was not owing to disagreements over the quality of Forrester’s work, but because of two consecutive sources of resistance. External resistance from publishers first led to the initial project being reduced to the translation of two seminars, whereas internal resistance from Lacan’s son-in-law Jacques-Alain Miller to Forrester’s vision of presenting the seminars with a full scholarly apparatus subsequently brought about delays in its execution