Once-daily fosamprenavir with ritonavir in the treatment of HIV infection in therapy-naïve patients

Treatment options for HIV patients have dramatically improved since the introduction of efficacious antiretroviral combination therapy more than a decade ago. Treatment regimens have been simplified with fewer pills and fewer daily dosages. Fosamprenavir is a protease inhibitor with a rather long half-life which makes it a candidate for once-daily use. Once-daily dosage of ritonavir-boosted fosamprenavir is approved in the US, but not in Europe, for treatment in patients without prior antiretroviral treatment. Here we review the background and rationale for once-daily dosage of ritonavir-boosted fosamprenavir. The rather limited studies that have been published so far indicate that fosamprenavir 1400 mg may be used once daily boosted with ritonavir. The optimal ritonavir dose to be given together with fosamprenavir is still to be defined, though available results indicate that a dose of 100 mg may be adequate provided that no protease inhibitor resistance is present

Retroviral rebound syndrome after treatment discontinuation in a 15 year old girl with HIV attracted through mother-to-child transmission: case report

A case of a 15 year old girl with retroviral rebound syndrome after discontinuation of highly active antiretroviral treatment (HAART) due to side effects is presented. The patient was transmitted with HIV at birth by her mother. She had recovered from severe AIDS after HAART was initiated five years earlier. This is the first case reported in the literature of retroviral rebound syndrome in a vertically transmitted HIV-infected patient

Cerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders.

Purpose of reviewThe aim of this study was to examine the synaptic biomarker neurogranin in cerebrospinal fluid (CSF) in different stages of HIV infection and in relation to what is known about CSF neurogranin in other neurodegenerative diseases.Recent findingsCSF concentrations of neurogranin are increased in Alzheimer's disease, but not in other neurodegenerative disorder such as Parkinson's disease, frontotemporal dementia, and Lewy body dementia. Adults with HIV-associated dementia have been found to have decreased levels of neurogranin in the frontal cortex, which at least to some extent, may be mediated by the proinflammatory cytokines IL-1β and IL-8. CSF neurogranin concentrations were in the same range for all groups of HIV-infected individuals and uninfected controls. This either indicates that synaptic injury is not an important part of HIV neuropathogenesis or that CSF neurogranin is not sensitive to the type of synaptic impairment present in HIV-associated neurocognitive disorders

Generating Personas for Games with Multimodal Adversarial Imitation Learning

Reinforcement learning has been widely successful in producing agents capable of playing games at a human level. However, this requires complex reward engineering, and the agent's resulting policy is often unpredictable. Going beyond reinforcement learning is necessary to model a wide range of human playstyles, which can be difficult to represent with a reward function. This paper presents a novel imitation learning approach to generate multiple persona policies for playtesting. Multimodal Generative Adversarial Imitation Learning (MultiGAIL) uses an auxiliary input parameter to learn distinct personas using a single-agent model. MultiGAIL is based on generative adversarial imitation learning and uses multiple discriminators as reward models, inferring the environment reward by comparing the agent and distinct expert policies. The reward from each discriminator is weighted according to the auxiliary input. Our experimental analysis demonstrates the effectiveness of our technique in two environments with continuous and discrete action spaces.Comment: Published in CoG 202

Improving Generalization in Game Agents with Data Augmentation in Imitation Learning

Imitation learning is an effective approach for training game-playing agents and, consequently, for efficient game production. However, generalization - the ability to perform well in related but unseen scenarios - is an essential requirement that remains an unsolved challenge for game AI. Generalization is difficult for imitation learning agents because it requires the algorithm to take meaningful actions outside of the training distribution. In this paper we propose a solution to this challenge. Inspired by the success of data augmentation in supervised learning, we augment the training data so the distribution of states and actions in the dataset better represents the real state-action distribution. This study evaluates methods for combining and applying data augmentations to observations, to improve generalization of imitation learning agents. It also provides a performance benchmark of these augmentations across several 3D environments. These results demonstrate that data augmentation is a promising framework for improving generalization in imitation learning agents.Comment: 8 pages, 5 figure

The Swedish COVID-19 approach: a scientific dialogue on mitigation policies

During the COVID-19 pandemic, Sweden was among the few countries that did not enforce strict lockdown measures but instead relied more on voluntary and sustainable mitigation recommendations. While supported by the majority of Swedes, this approach faced rapid and continuous criticism. Unfortunately, the respectful debate centered around scientific evidence often gave way to mudslinging. However, the available data on excess all-cause mortality rates indicate that Sweden experienced fewer deaths per population unit during the pandemic (2020–2022) than most high-income countries and was comparable to neighboring Nordic countries through the pandemic. An open, objective scientific dialogue is essential for learning and preparing for future outbreaks

Neurochemical biomarkers to study CNS effects of COVID-19: a narrative review and synthesis

Neurological symptoms are frequently reported in patients suffering from COVID-19. Common CNS-related symptoms include anosmia, caused by viral interaction with either neurons or supporting cells in nasal olfactory tissues. Diffuse encephalopathy is the most common sign of CNS dysfunction, which likely results from the CNS consequences of the systemic inflammatory syndrome associated with severe COVID-19. Additionally, microvascular injuries and thromboembolic events likely contribute to the neurologic impact of acute COVID-19. These observations are supported by evidence of CNS immune activation in cerebrospinal fluid (CSF) and in autopsy tissue, along with detection of microvascular injuries in both pathological and neuroimaging studies. The frequent occurrence of thromboembolic events in patients with COVID-19 has generated different hypotheses, among which viral interaction with perivascular cells is particularly attractive, yet unproven. A distinguishing feature of CSF findings in SARS-CoV-2 infection is that clinical signs characteristic of neurotropic viral infections (CSF pleocytosis and blood brain barrier injury) are mild or absent. Moreover, virus detection in CSF is rare, and often of uncertain significance. In this review, we provide an overview of the neurological impact that occur in the acute phase of COVID-19, and the role of CSF biomarkers in the clinical management and research to better treat and understand the disease. In addition to aiding as diagnostic and prognostic tools during acute infection, the use of comprehensive and well characterized CSF and blood biomarkers will be vital in understanding the potential impact on the CNS in the rapidly increasing number of individuals recovering from COVID-19

Blood biomarkers for HIV infection with focus on neurologic complications-A review

Although clinical examinations, neuroimaging, and cerebrospinal fluid analyses are the most important ways to evaluate the impact of HIV infection on the brain and in diagnosis of opportunistic infections, several blood biomarkers including HIV RNA concentrations, CD4 +T-cell count, and neurofilament light chain protein (NfL) concentration, along with tests for opportunistic infections can provide important information for clinical decisions