Sérgio Monteiro de Almeida

Relationship of antiretroviral treatment to postmortem brain tissue viral load in human immunodeficiency virus–infected patients

Human immunodeficiency virus (HIV)-1 invades the central nervous system (CNS) soon after infection and is partially protected there from host immunity and antiretroviral drugs (ARVs). Sanctuary from highly active antiretroviral therapy (HAART) in the CNS could result in ongoing viral replication, promoting the development of drug resistance and neurological disease. Despite the importance of these risks, no previous study has directly assessed HAART’s effects on brain tissue viral load (VL). The authors evaluated 61 HIV-infected individuals for whom both histories of HAART treatment and postmortem brain tissue VL measurements were available. Two groups were defined based on HAART use in the 3 months prior to death: HAART(+) subjects had received HAART, and HAART(−) subjects had not received HAART. HIV RNA was quantified in postmortem brain tissue (log10 copies/10 μg total tissue RNA) and antemortem plasma (log10 copies/ml) by reverse transcriptase—polymerase chain reaction (RT-PCR). Brain tissue VLs were significantly lower among HAART(+) subjects compared to HAART(−) subjects (median 2.6 versus 4.1; P = .0007). These findings suggest that despite the limited CNS penetration of many antiretroviral medications, HAART is at least partially effective in suppressing CNS viral replication. Because some HAART regimens may be better than others in this regard, regimen selection strategies could be used to impede CNS viral activity, limit neuronal dysfunction, and prevent or treat clinical neurocognitive disorders in HIV-infected patients. Furthermore, such strategies might help to prevent the development of ARV resistance.

Central Nervous System Paracoccidioidomycosis: An Overview

Paracoccidioidomycosis (PCM) is an infectious disease, endemic to subtropical areas of Central and South America, caused by the dimorphic fungus Paracoccidioides brasiliensis. It is a chronic disease, mostly affecting adult males, with a mean patient age of 44 years. Central nervous system involvement (CNS PCM) has been found in 13% of the patients with systemic disease. We reviewed the clinical presentation, diagnosis techniques and treatments for CNS PCM.

Dynamics of monocyte chemoattractant protein type one (MCP-1) and HIV viral load in human cerebrospinal fluid and plasma

BACKGROUND Increased expression of monocyte chemoattractant protein type 1 (MCP-1) is associated with HIV CNS disease. This study evaluated the temporal relationships between MCP-1 expression and HIV replication in the CNS. METHODS MCP-1 and HIV viral load (VL) were measured in serially obtained samples of plasma and cerebrospinal fluid (CSF) in subjects either interrupting (TI) or starting (TS) antiretroviral therapy. RESULTS Following TI, plasma VL rebounded first, followed by increases in CSF MCP-1, which immediately preceded or coincided with a rebound of CSF VL. CONCLUSION The close temporal relationship of the increase of MCP-1 and CSF VL suggests that they are co-regulated, or that one is a stimulus for the other.

Incidence of Post‐Dural Puncture Headache in Research Volunteers

Objective.— To determine the frequency and risk factors of post‐dural puncture headache (PDPH) in research volunteers.

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

Pneumococcal meningitis is a life-threatening disease characterized by an acute purulent infection affecting piamater, arachnoid and the subarachnoid space. The intense inflammatory hosts response is potentially fatal and contributes to the neurological sequelae. Streptococcus pneumoniae colonizes the nasopharynx, followed by bacteremia, microbial invasion and blood-brain barrier traversal. S. pneumoniae is recognized by antigen-presenting cells through the binding of Toll-like receptors inducing the activation of factor nuclear kappa B or mitogen-activated protein kinase pathways and subsequent up-regulation of lymphocyte populations and expression of numerous proteins involved in inflammation and immune response. Many brain cells can produce cytokines, chemokines and others pro-inflammatory molecules in response to bacteria stimuli, as consequence, polymorphonuclear are attracted, activated and released in large amounts of superoxide anion and nitric oxide, leading to the peroxynitrite formation, generating oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage, blood-brain barrier breakdown contributing to cell injury during pneumococcal meningitis.

Neurocognitive Impairment in HIV-1 Clade C versus B Infected Individuals in Southern Brazil

HIV-1 clade C isolates show reduced Tat protein chemoattractant activity compared with clade B. This might influence neuropathogenesis by altering trafficking of monocytes into the CNS. A previous study suggested low rates of HIV-associated dementia in clade C-infected individuals. The present study evaluated neurocognitive impairment rates in clade B- and C-infected individuals from the same local population. HIV+ and HIV− participants were recruited from the same geographic region in Southern Brazil. We evaluated neuropsychological (NP) impairment using a screening instrument (the International HIV Dementia Scale (IHDS)), as well as a Brazilian Portuguese adaptation of a comprehensive battery that has demonstrated sensitivity to HIV-associated neurocognitive disorders (HAND) internationally. NP performance in controls was used to generate T scores and impairment ratings by the global deficit score (GDS) method. Clade assignments were ascertained by sequencing pol and env. Blood and cerebrospinal fluid were collected from all HIV+ participants. HIV+ and HIV− participants were comparable on demographic characteristics. HIV+ participants overall were more likely to be impaired than HIV− by the IHDS and the GDS. Clade B- and C-infected individuals were demographically similar and did not differ significantly in rates of impairment. The prevalence of pleocytosis, a marker of intrathecal cellular chemotaxis, also did not differ between clade B and C infections. Clade B and C HIV-infected individuals from the same geographic region, when ascertained using comparable methods, did not differ in their rates of neurocognitive impairment, and there was no evidence of differences in CNS chemotaxis.

Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis.

Syphilis is a frequent coinfection with human immunodeficiency virus (HIV). Whereas systemic syphilis infection increases plasma HIV RNA levels (viral load; VL), effects of syphilis on cerebrospinal fluid (CSF) VL are unknown. We hypothesized that intrathecal immune activation in neurosyphilis would selectively increase CSF VL in coinfected patients. In this study, HIV-infected research subjects (N = 225) were categorized into three groups based on serum rapid plasma reagin (RPR), microhemaglutination for Treponema pallidum (MHA-TP) MHA-TP, and CSF VDRL: 23 with neurosyphilis (NS +; reactive serum RPR and MHA-TP and positive CSF VDRL); 42 with systemic syphilis but not neurosyphilis (Syph+; reactive serum RPR and MHA-TP; negative CSF VDRL), and 160 without syphilis (Syph−; nonreactive serum RPR). Plasma and CSF HIV VL were quantified by reverse transcriptase—ploymerase chain reaction (RT-PCR) (Amplicor, Roche) in log10 copies/ml. To adjust for covariates previously shown to influence CSF HIV VL (i.e., plasma VL, CD4, pleocytosis, and highly active antiretroviral therapy [HAART]), multivariable linear regression was used. Lumbar punctures (LP) done for research purposes diagnosed 23 with neurosyphilis; most (83%) of these reported prior syphilis treatment. Among subjects with detectable plasma VL, CSF VL was highest in NS+, followed by Syph+ and Syph− (P =.006). This relationship was independent of the level of plasma VL or CSF pleocytosis. By contrast, among subjects with undetectable plasma HIV VL, CSF VLs were similar in the three syphilis subgroups (P = .50). Neurosyphilis may amplify intrathecal HIV replication, possibly through immune activation that persists even after syphilis treatment. Because elevated CSF VL is associated with subsequent neurocognitive decline, future studies should evaluate the impact of neurosyphilis on the course of central nervous system (CNS) HIV infection.

Human immunodeficiency virus and the central nervous system

The pandemic of HIV/AIDS continues to grow daily. Incident cases among women, intravenous drug users and ethnic minorities comprise the fastest growing segment of the HIV-infected population, and the number of HIV-infected individuals over the age of 50 is growing rapidly. Today, the central nervous system and the immune system are seen as main targets of HIV infection. Significant progress in the knowledge and treatment of AIDS has been obtained in recent years. The neurological manifestations directly related to HIV are acute viral meningitis, chronic meningitis, HIV-associated dementia (HAD), vacuolar myelopathy, and involvement of the peripheral nervous system.

Relationship of CSF leukocytosis to compartmentalized changes in MCP-1/CCL2 in the CSF of HIV-infected patients undergoing interruption of antiretroviral therapy

Although monocyte chemoattractant protein (MCP-1)/CCL2 is believed to mediate trafficking of HIV-activated leukocytes into the CNS, its role has not been studied directly in humans. To evaluate MCP-1s effects on CNS leukocyte infiltration, we measured CSF leukocytes and MCP-1 levels in serial plasma and cerebrospinal fluid (CSF) samples from subjects who experienced large increases in viral load after interrupting antiretrovirals. Following large increases in CSF MCP-1, CSF leukocytosis (15-166 cells/microL) developed in 4 of 6 subjects. Both initial MCP-1 levels and subsequent changes were 3-fold larger in CSF than plasma. The magnitude and timing of changes suggested that MCP-1 triggers the development of CSF pleocytosis.

Bilateral peripheral facial palsy secondary to lymphoma in a patient with HIV/AIDS: a case report and literature review

Neurological complications represent one of the most important causes of morbidity and mortality in patients with HIV/AIDS. However, peripheral neuropathy comprises only 5% to 20% of the total neurological complications and facial nerve palsy, especially when it is bilateral, is a less common manifestation. Peripheral facial palsy has been considered as a possible neurological complication of the early stage of HIV infection but the number of reported cases in the literature is limited. Histological findings of nervous tissue in peripheral facial palsy at an early stage of HIV infection include a degenerative and not suppurative inflammatory process, but its etiology remains obscure. Peripheral facial palsy in the late stage of HIV infection is characterized by an advanced immunological deficit and generally it is secondary to an opportunistic infection of the CNS, such as neurotoxoplasmosis and lymphoma. However, this peripheral attack of the facial nerve is not very common at this late stage of HIV infection. Bilateral peripheral facial palsy as a complication of non-Hodgkin s lymphoma is considered an extremely rare entity. There are no published reports of bilateral peripheral facial palsy secondary to lymphomas or other neoplasms of the CNS in immunosuppressed patients. Non-Hodgkin s lymphoma (NHL) has been considered a late and relatively common manifestation of HIV infection, but an exact cause for the higher incidence of this malignant neoplasm in HIV/AIDS patients is still uncertain.