Limited recovery from post-acute sequelae of SARS-CoV-2 at 8 months in a prospective cohort.

In a longitudinal cohort, a significant proportion of patients had persistent symptoms 8 months after initial #COVID19 infection. There was no significant improvement in symptoms or health-related quality of life between 4- and 8-month assessments. https://bit.ly/2Wtb7IX.

MR spectroscopy in HIV associated neurocognitive disorder in the era of cART: a review.

Neuroimaging has been a critical tool for understanding the neuropathological underpinnings observed in HIV. The pathophysiology of HAND is chiefly driven by neuroinflammation. Despite adhering to cART, low levels of viraemia probably persist in the brain in some patients leading to chronic immune activation with resultant neuroinflammation and consequent neuronal injury. MR spectroscopy has been widely used as a biomarker for the presence and severity of HAND in several studies. By studying the MRS signatures, it is possible to characterise the presence of neuroinflammation and neural injury. Furthermore, metabolite concentrations measured by MRS could be used as a quantitative indicator of HIV cerebral involvement, thereby affording the opportunity to assess the efficacy of cART in HAND. However, currently there are three significant limitations in the MRS HIV research literature: the relative paucity of prospective studies, the small number of regions of interrogation due to current methodology (single voxel MRS), and the evolving understanding of the impact of co-morbidities (e.g. ageing, mood disorders, alcoholism etc.) on MRS measurements. This review critically addresses the current literature of MRS studies in people living with HIV (PWH) with HAND to determine its value, especially in the context of the current cART era. In addition, we discuss technical considerations related to the disease and the future direction in HAND using MRS.

HIV-1 viral blips are associated with repeated and increasingly high levels of cell-associated HIV-1 RNA transcriptional activity.

OBJECTIVE: Some HIV+ patients, virally suppressed on ART, show occasional 'blips' of detectable HIV-1 plasma RNA. We used a new highly sensitive assay of cell-associated HIV-1 RNA to measure transcriptional activity in PBMCs and production of infectious virus from the viral reservoir, in patients with and without 'blips'. DESIGN/METHODS: RNA and DNA extracted from cells in 6 ml of peripheral blood, from suppressed patients with one to two 'blip' episodes over the past 2 years of ART (n = 55), or no 'blips' (n = 52), were assayed for HIV-1 RNA transcripts and proviral DNA targeting the highly conserved 'R' region of the LTR. Follow-up samples were also collected. Purified CD4+ T cells were cultured with anti-CD3/CD28/CD2 T-cell activator to amplify transcription and measure replication competent virus. RESULTS: HIV-1 RNA transcripts ranged from 1.3 to 5415 copies/106 white blood cells. 'Blip' patients had significantly higher levels vs. without blips (median 192 vs. 49; P = 0.0007), which correlated with: higher levels of inducible transcripts after activation in vitro, sustained higher HIV-1 transcription levels in follow-up samples along with increasing HIV-1 DNA in some, and production of replication-competent HIV-1. CONCLUSION: Viral 'blips' are significant reflecting higher transcriptional activity from the reservoir and contribute to the reservoir over time. This sensitive assay can be used in monitoring the size and activity of the HIV-1 reservoir and will be useful in HIV-1 cure strategies.

Human Immunodeficiency Virus and the Nervous System.

In the era of combination antiretroviral therapy, the diagnosis and management of HIV-associated neurocognitive disorders (HANDs) has arisen. Traditionally, severe HAND was seen in those with untreated HIV infection and had a guarded prognosis. Antiretroviral therapy has provided longevity and viral control to many living with the disease, revealing an increase in prevalence of less severe forms of HAND. Despite peripheral blood and cerebrospinal fluid viral suppression, cognitive impairment occurs and progresses for reasons that are unclear at present. This article provides a review of current theories behind the development of HAND, clinical and pathologic findings, recent developments, and future research opportunities.

Introduction to HIV infection and HIV neurology.

In this introductory chapter the impact of combination antiretriviral therapy is discussed. Three different "types" of HIV infection are described according to medication adherence and efficacy. Next, general principles of HIV related neurologic complications are defined. Last, a clinical approach to the HIV infected patient with a neurologic complication is then detailed.

Progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a relatively common complication of HIV disease. In this chapter changes to the epidemiology are discussed along with an update in its pathogenesis and treatment. Immune reconstitution inflammatory syndrome is increasingly frequent in PML; accordingly management strategies and prognosis are detailed.

Neurologic sequelae of primary HIV infection.

Primary human immunodeficiency virus type 1 (HIV-1) infection is defined as the period from initial infection with HIV to complete seroconversion. Neurologic sequelae of primary HIV-1 infection are not uncommon, potentially affecting all parts of the nervous system. It is important for the neurologist to be aware of symptomatic primary HIV infection, as it may afford an early and accurate diagnosis of HIV infection and the opportunity for consideration of early antiretroviral therapy. This chapter introduces the clinical manifestations of primary HIV infection, including the laboratory and diagnostic approach, before detailing the various neurologic sequelae. Finally the treatment of primary HIV infection and neurologic sequelae are discussed, in the context of recent advances in the field of HIV reservoirs and longer-term neurologic complications.

HIV-associated neurocognitive disorder.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects roughly half the HIV-positive population. The symptoms of cognitive slowing, poor concentration, and memory problems can impact on everyday life. Its diagnosis is validated where possible by identifying deficits in two cognitive domains on neuropsychologic testing in patients either with or without symptoms. Corroborating evidence may be found on imaging, blood tests, and cerebrospinal fluid analysis, though sensitive and specific biomarkers are currently lacking. The introduction of combined antiretroviral therapy in the 1990s has generated a therapeutic paradox whereby the number of severe cases of HAND has fallen, yet milder forms continue to rise in prevalence. New emphasis has been placed on identifying the cause of apparent ongoing HIV infection and inflammation of the central nervous system (CNS) in the face of durable systemic viral suppression, and how this equates to the neuronal dysfunction underlying HAND. The interaction with aging and comorbidities is becoming increasingly common as the HIV-positive population enters older adulthood, with neurodegenerative, metabolic, and vascular causes of cognitive impairment combining and probably accelerating in the context of chronic HIV infection. Therapies targeted to the CNS, but without neurotoxic side-effects, are being investigated to attempt to reduce the likelihood of developing, and improving, HAND.

Biomarkers of HIV related central nervous system disease.

In this review we critically assess biomarkers of the direct effects of HIV related brain disease. This area is becoming increasingly complex because of the presence of confounds and varying degrees of activity of HIV brain disease. Sensitive and specific biomarkers are urgently needed although existing biomarkers do have some utility. The review will focus on the practical implications of the more established biomarkers. We discuss blood, cerebrospinal fluid and neurophysiological biomarkers but not neuroimaging techniques as they are beyond the scope of this review.