Winona Poulton

Protein changes in CSF of HIV-infected patients: evidence for loss of neuroprotection

To begin to unravel the complexity of HIV-associated changes in the brain, broader, multifaceted analyses of cerebrospinal fluid (CSF) are needed that examine a wide range of proteins reflecting different functions. To provide the first broad profiles of protein changes in the CSF of HIV-infected patients, we used antibody arrays to measure 120 cytokines, chemokines, growth factors, and other proteins. CSF from HIV-infected patients with a range of cognitive deficits was compared to CSF from uninfected, cognitively normal patients to begin to identify protein changes associated with HIV infection and neurological disease progression. Uninfected patients showed relatively consistent patterns of protein expression. Highly expressed proteins in CSF included monocyte chemotactic protein-1, tissue inhibitors of metalloproteases, granulocyte colony-stimulating factor, adiponectin, soluble tumor necrosis factor receptor-1, urokinase-type plasminogen activator receptor, and insulin-like growth factor binding protein-2. Inflammatory and anti-inflammatory cytokines were expressed at low levels. HIV-infected patients showed increases in inflammatory proteins (interferon-gamma, tumor necrosis factor-alpha), anti-inflammatory proteins (IL-13), and chemokines but these correlated poorly with neurological status. The strongest correlation with increasing severity of neurological disease was a decline in growth factors, particularly, brain-derived neurotrophic factor and NT-3. These studies illustrate that HIV infection is associated with parallel changes in both inflammatory and neuroprotective proteins in the CSF. The inverse relationship between growth factors and neurological disease severity suggests that a loss of growth factor neuroprotection may contribute to the development of neural damage and may provide useful markers of disease progression.

Pregnant and Nonpregnant Women in Cape Town, South Africa: Drug Use, Sexual Behavior, and the Need for Comprehensive Services

The multiple risks associated with methamphetamine use are of serious concern for women. These risks and consequences are magnified during pregnancy. This secondary analysis of a parent study compared 26 pregnant to 356 nonpregnant women in Cape Town, South Africa, on selected demographic, psychosocial, and HIV-risk domains to identify their treatment service needs. Proportionally, more pregnant than nonpregnant women are using methamphetamine, P = .01, although a very high rate of women used methamphetamine. Women reported similar monthly rates of sexual intercourse, but pregnant women were significantly less likely to report condom use, P < .0001, maintaining their risky behavior. Both groups reported elevated Center for Epidemiological Studies Depression Scale CES-D means, suggesting a need for depression treatment. Results demonstrate a pervasive need for womens comprehensive treatment, regardless of pregnancy status. Moreover, findings support the urgent need for women-focused and pregnancy-specific treatment services for methamphetamine use. Finally, a job-skills training/employment component focus is suggested.

Novel p75 neurotrophin receptor ligand stabilizes neuronal calcium, preserves mitochondrial movement and protects against HIV associated neuropathogenesis

Human immunodeficiency virus (HIV) rapidly penetrates into the brain and establishes a persistent infection of macrophages/microglia. Activation of these cells by HIV results in the secretion of soluble factors that destabilize neuronal calcium homeostasis, encourage oxidative stress and result in neural damage. This damage is thought to underlie the cognitive-motor dysfunction that develops in many HIV-infected patients. Studies have suggested that neurotrophins may protect neurons from the toxic effects of HIV-associated proteins. To better understand the pathogenic mechanisms and the neuroprotective potential of neurotrophin ligands, we evaluated neuronal damage, calcium homeostasis and mitochondrial functions after exposure of cultured rat neurons directly to HIV gp120 or to conditioned medium from human monocyte-derived macrophages treated with gp120. We then assessed the ability of a new non-peptide p75 neurotrophin receptor ligand, LM11A-31, to stabilize calcium homeostasis and prevent the development of pathology. Each toxic challenge resulted in a delayed accumulation of intracellular calcium coupled to a decrease in the rate of calcium clearance from the cell. The delayed calcium accumulation correlated with the development of focal dendritic swellings (beading), cytoskeletal damage and impaired movement of mitochondria. Addition of LM11A-31 to the cultures at nanomolar concentrations eliminated cell death, significantly reduced the pathology, suppressed the delayed accumulation of calcium and restored mitochondrial movements. The potent neuroprotection and the stabilization of calcium homeostasis indicate that LM11A-31 may have excellent potential for the treatment of HIV-associated neurodegeneration.

Results of a pilot study to reduce methamphetamine use and sexual risk behaviors among methamphetamine-using men who have sex with men (MSM) not currently in treatment.

Abstract Methamphetamine use, which has been linked to unprotected anal intercourse and incident HIV infection, is an important contributor to HIV transmission among men who have sex with men (MSM). The purpose of this study was to develop and pilot test a single-session motivational interviewing (MI) intervention for reducing HIV risk among an out-of-treatment sample of MSM who use methamphetamine. MSM who use methamphetamine (n = 39) were recruited in 2008 and 2009 in North Carolina. They completed baseline data collection and a single-session MI intervention. Eighty percent completed a follow-up interview two months after enrollment. Men reported reductions in methamphetamine use during the previous 60 days from an average of 9.4 days at baseline to 3.3 days at follow-up (p < 0.05) and unprotected anal intercourse from an average of 4.8 sex partners during the previous 60 days at baseline to 2.9 at follow-up (p < 0.05). Self-reported unprotected anal intercourse at last sex with a nonprimary partner decreased significantly (from 81% at baseline to 25% at follow-up; p = 0.001). These results suggest that a single-session MI intervention may be useful for reducing methamphetamine use and sexual risk among MSM who use methamphetamine, especially in settings where multisession interventions are not feasible.

Initial Feasibility of a Woman-Focused Intervention for Pregnant African-American Women

African-American women who use crack are vulnerable to HIV because of the complex social circumstances in which they live. Drug-abuse treatment for these women during pregnancy may provide time for changing risk behaviors. This paper examines the initial 6-month feasibility of a women-focused HIV intervention, the Womens CoOp, adapted for pregnant women, relative to treatment-as-usual among 59 pregnant African-American women enrolled in drug-abuse treatment. At treatment entry, the women were largely homeless, unemployed, practicing unsafe sex, and involved in violence. Results indicated marked reductions in homelessness, use of cocaine and illegal drugs, involvement in physical violence, and an increase in knowledge of HIV from baseline to 6-month followup for both conditions. Findings suggest that the Womens CoOp intervention could be successfully adapted to treat this hard-to-reach population. Future studies should examine the efficacy of the pregnancy-adapted Womens CoOp for women not enrolled in drug-abuse treatment.

Adapting an evidence-based HIV prevention intervention for pregnant African-American women in substance abuse treatment

An adaptation of an evidence-based, woman-focused intervention designed to reduce HIV risk behaviors was conducted for pregnant, African-American women in substance abuse treatment in North Carolina. The intervention adaptation process included focus groups, expert panels, and the filming of women who spoke about their experiences with pregnancy, drug use, sex risk behaviors, HIV testing and treatment, need for substance abuse treatment, violence, and victimization. The assessment instrument was adapted for pregnant women and the intervention was organized into a 4-session PowerPoint presentation, with an additional session if a woman tested positive for HIV. All sessions and assessment instrument were installed on laptop computers for portability in treatment programs. We pilot tested our adaptation with 59 pregnant African-American women who had used an illicit drug within the past year and were enrolled in substance abuse treatment. At baseline, 41% were currently homeless, 76% were unemployed, 90% had not planned their current pregnancy, and approximately 70% reported drug use since finding out about the pregnancy. This sample of participants rated the intervention sessions and were highly satisfied with their experience, resulting in a mean satisfaction score of 6.5 out of 7. Pregnant African-American women who use drugs need substance abuse treatment that they do not currently access. Woman-focused HIV interventions help to address intersecting risk behaviors and need for treatment prevalent among this vulnerable group.