Informing Informed Consent for HIV Research.

"Respect for Persons" is an ethical principle demonstrated through the informed consent process. Participants at a large HIV research center were surveyed to identify important aspects of the consent process. Persons with and without HIV ( = 103) completed a short pre/post questionnaire with both open-ended and forced choice response options.

Portable lactate analyzer for measuring lactate in cerebrospinal fluid (CSF) and plasma - method-comparison evaluations.

Unlabelled: Increased plasma lactate levels can indicate the presence of metabolic disorders in HIV infected individuals.

Objective: To determine whether a portable analyzer is valid for measuring cerebrospinal fluid (CSF) and plasma lactate levels in HIV infected individuals.

Method: CSF and plasma were collected from 178 subjects.

Family history of dementia predicts worse neuropsychological functioning among HIV-infected persons.

HIV-negative individuals with a family history of dementia (FHD) are more likely to develop dementia than those without FHD. Whether FHD increases risk for neuropsychological (NP) impairment in HIV+ persons is unknown. As part of a multisite study into HIV-associated neurocognitive disorders (HAND), the authors captured FHD with a free-response, self-report question, and assessed NP performance with a comprehensive battery of tests.

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.

Background: Despite increasing interest in measuring cerebrospinal fluid (CSF) biomarkers to investigate disease pathogenesis and diagnosis, previous case series have evaluated lumbar puncture (LP) safety only in clinical care. PDPH is a common complication after LP.

Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals.

Chemokines influence HIV neuropathogenesis by affecting the HIV life cycle, trafficking of macrophages into the nervous system, glial activation, and neuronal signaling and repair processes; however, knowledge of their relationship to in vivo measures of cerebral injury is limited. The primary objective of this study was to determine the relationship between a panel of chemokines in cerebrospinal fluid (CSF) and cerebral metabolites measured by proton magnetic resonance spectroscopy (MRS) in a cohort of HIV-infected individuals. One hundred seventy-one stored CSF specimens were assayed from HIV-infected individuals who were enrolled in two ACTG studies that evaluated the relationship between neuropsychological performance and cerebral metabolites.

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.

Role of metabolic syndrome components in HIV-associated sensory neuropathy.

Objectives: Sensory neuropathy is a common peripheral nerve complication of HIV infection and highly active antiretroviral therapy. Metabolic syndrome (MetS), a cluster of risk factors for atherosclerosis and microvascular disease, is associated with sensory neuropathy in HIV-uninfected (HIV-negative) persons. We examined whether MetS or its components predispose individuals to HIV-associated sensory neuropathy (HIV-SN).

Role of metabolic syndrome components in human immunodeficiency virus-associated stroke.

Metabolic syndrome (MetS) is a cluster of risk factors, including elevated mean arterial pressure (MAP), atherogenic dyslipidemia (elevated triglycerides [TRG]), abdominal obesity (increased body mass index [BMI]), glucose intolerance (elevated glucose [GLU]), and prothrombotic/inflammatory state (increases in uric acid [UA]), that are associated with increased risk of cerebrovascular disease. We studied if an association existed between MetS components and human immunodeficiency virus (HIV)-associated cryptogenic strokes-those not caused by HIV complications, endocarditis, or stimulant abuse. We performed a retrospective case-control study.

Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy.

Objective: Two recent analyses found that exposure to protease inhibitors (PIs) in the context of antiretroviral (ARV) therapy increased the risk for distal sensory polyneuropathy (DSPN) in subjects with human immunodeficiency virus (HIV) infection. These findings were supported by an in vitro model in which PI exposure produced neurite retraction and process loss in dorsal root ganglion sensory neurons. Confirmation of peripheral nerve toxicity with PIs could substantially limit their long-term use in highly active ARV therapy.

Validation of the CNS Penetration-Effectiveness rank for quantifying antiretroviral penetration into the central nervous system.

Objective: To evaluate whether penetration of a combination regimen into the central nervous system (CNS), as estimated by the CNS Penetration-Effectiveness (CPE) rank, is associated with lower cerebrospinal fluid (CSF) viral load.

Design: Data were analyzed from 467 participants who were human immunodeficiency virus (HIV) seropositive and who reported antiretroviral (ARV) drug use. Individual ARV drugs were assigned a penetration rank of 0 (low), 0.

The role of cohort studies in drug development: clinical evidence of antiviral activity of serotonin reuptake inhibitors and HMG-CoA reductase inhibitors in the central nervous system.

Background: Effective antiretroviral therapy (ART) has reduced the incidence of HIV-associated neurocognitive impairment (HNCI) but its prevalence remains high. Clinical trials have yet to identify a consistently effective treatment for HNCI, other than ART, but in vitro data support that some drugs approved by the Food and Drug Administration (FDA) for other indications might benefit individuals with HNCI. Some of these drugs, such as serotonin reuptake inhibitors (SRIs) and HMG-CoA reductase inhibitors (statins), may do so by reducing HIV replication in the CNS and are already widely used by HIV-infected individuals.

Predictive validity of demographically adjusted normative standards for the HIV Dementia Scale.

The aim of the current study was to develop and validate demographically adjusted normative standards for the HIV Dementia Scale (HDS). Given the association between demographic variables and the HDS summary score, demographically adjusted normative standards may enhance the classification accuracy of the HDS. Demographically adjusted normative standards were derived from a sample of 182 seronegative healthy participants and were subsequently applied to a sample of 135 HIV-1 seropositive individuals with multidisciplinary case conference diagnoses of HIV-1-associated neurocognitive disorders (e.

Markers of macrophage activation and axonal injury are associated with prospective memory in HIV-1 disease.

Objective: To use clinical specimens to better understand the neuropathogenesis of prospective memory (ProM) functioning in persons with HIV-1 infection.

Background: Emergent evidence suggests that HIV-1 is associated with impaired ProM, but the underlying neuropathophysiology of this deficit is not known.

Methods: Thirty-five nondemented subjects with HIV-1 infection completed measures of both ProM (ie, memory for future intentions) and retrospective memory (RM; ie, memory for past episodes).

Valproic acid does not affect markers of human immunodeficiency virus disease progression.

Valproic acid (VPA) reduces latent human immunodeficiency virus (HIV) reservoirs by activating resting CD4+ cells. This retrospective case-control study (n = 30) examined effects of VPA on markers of HIV progression. VPA was not associated with changes in cerebrospinal fluid viral loads (VL), plasma VL, or neuropsychological performance.

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 effects of hepatitis C, HIV, and methamphetamine dependence on neuropsychological performance: biological correlates of disease.

Objective: To determine the effects of hepatitis C virus (HCV) infection on neuropsychological (NP) performance.

Design: Cross-sectional analysis of a prospectively enrolled cohort.

Methods: A total of 239 HIV-seropositive and 287 HIV-seronegative subjects enrolled in prospective cohort studies at a single center.

Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV.

Introduction: Lopinavir (LPV) is highly bound to plasma proteins and is a substrate for active drugs transporters, which may greatly limit the access of LPV to the central nervous system (CNS). However, even low lopinavir concentrations may be sufficient to inhibit HIV replication. Prior anecdotal reports indicated that lopinavir concentrations were below detection in cerebrospinal fluid (CSF).

The monocyte chemotactic protein-1 -2578G allele is associated with elevated MCP-1 concentrations in cerebrospinal fluid.

Because monocyte chemotactic protein (MCP)-1 is an important cofactor in HIV neuropathogenesis, we investigated the relationship between MCP-1 genotype and expression in cerebrospinal fluid (CSF). We evaluated a genetic polymorphism in the MCP-1 promoter at position -2578 (alternatively designated -2518) in 98 HIV-infected subjects who had contemporaneously collected plasma and CSF. CSF MCP-1 levels were highest in the G/G genotype group, intermediate in the G/A group, and lowest in the A/A group.

CCR2 polymorphisms affect neuropsychological impairment in HIV-1-infected adults.

CCR2 is a minor coreceptor for human immune deficiency virus-1 (HIV-1) and its impact on HIV-1-related neuropsychological impairment (NPI) remains unknown. We studied the impact of CCR2-V64I polymorphisms on the development of NPI in 121 HIV-1 patients. The CCR2-64-I allele was associated with rate of progression to NPI when measured from the first study visit (Log Rank p=0.