Low Levels of Endothelial Progenitor Cells and Their Association with Systemic Inflammation and Monocyte Activation in Older HIV-Infected Men.

Endothelial progenitor cells (EPCs) repair damaged vascular endothelium, and low circulating EPC levels have been associated with cardiovascular disease (CVD). CD34+/KDR+ EPCs are commonly reported in the literature and CD34+/CD133+/KDR+ EPCs are rare in circulation but highly specific for endothelial lineage. HIV-infected (HIV+) adults have chronic inflammation and increased CVD risk, but the relationship between CVD, vascular inflammation, and EPCs in HIV remains unclear. In a pilot study, EPCs were measured in 57 HIV+ men [≥50 years old, HIV-1 RNA <50 copies/ml on antiretroviral therapy (ART)] by real-time flow cytometry using cellular immaturity (CD34 and/or CD133) and endothelial commitment (KDR) markers. Fasting inflammatory biomarker levels were measured by ELISA. Median age was 57 years; CD4+ T lymphocyte count was 570 cells/mm3. Prevalent CVD risk factors included 16% diabetes, 28% hypertension, 53% dyslipidemia, and 33% smoking. Median (interquartile range) EPC values were CD34+/KDR+ 0.1 (0.0-0.9) cells/105 peripheral blood mononuclear cells (PBMCs) and CD34+/CD133+/KDR+ 0.1 (0.0-0.9) cells/105 PBMCs. We observed a high prevalence of undetectable CD34+/KDR+ (40%) and CD34+/CD133+/KDR+ EPCs (44%). Men with undetectable EPCs were more likely to have ≥2 CVD risk factors, lower interleukin-6 (IL-6), and higher sCD163 levels. In these older HIV+ men on suppressive ART, CD34+/KDR+ and CD34+/CD133+/KDR+ EPC levels were low and often undetectable. Undetectable EPC levels were associated with greater CVD risk factor burden, lower IL-6 (consistent with decreased EPC production stimulus), and higher sCD163 (consistent with monocyte activation and prior CVD associations) levels, suggesting a potential relationship between EPCs and atherosclerotic burden in this population.

An assessment of polymorphonuclear leukocyte rigidity in HIV-infected individuals after immune recovery.

PURPOSE: To determine whether polymorphonuclear leukocytes (PMNs) remain rigid after immune reconstitution in human immunodeficiency virus (HIV)-infected individuals with a history of severe immunosuppression. METHODS: PMN rigidity was measured in vitro in three groups: (1) HIV-infected individuals with a history of CD4+ T-lymphocyte counts of less than 50/microL, but with current counts of more than 200/microL attributable to potent antiretroviral therapy (group 1); (2) HIV-infected individuals whose CD4+ T-lymphocyte counts had always been more than 200/microL (group 2); and (3) HIV-negative control subjects. Rigidity was determined with a cell transit analyzer (containing a micropore filter with 30 identical, 8-microm diameter pores), representing a simple in vitro model of a capillary bed. A longer PMN pore transit time reflects increased PMN rigidity. RESULTS: PMN transit time (median) in group 1 (n = 11) was 3.34 ms, in group 2 (n = 9) was 3.19 ms, and in control subjects (n = 15) was 2.66 ms. PMN rigidity was significantly greater in groups 1 (P = 0.014) and 2 (P = 0.046) than in control subjects (Wilcoxon rank-sum test). A significant difference was not identified between groups 1 and 2 (P = 0.518). CONCLUSIONS: The increased PMN rigidity known to occur in severely immunosuppressed HIV-infected individuals persists after immune reconstitution. Furthermore, PMN rigidity is increased in those HIV-infected individuals who do not have a history of severe immunosuppression. Because PMN rigidity can alter microvascular blood flow, HIV-infected individuals may remain at risk for retinal vascular damage in the era of potent antiretroviral therapy.

Prevalence, distribution, and correlates of hepatitis C virus infection among homeless adults in Los Angeles.

OBJECTIVE: We documented the prevalence, distribution, and correlates of hepatitis C virus (HCV) infection among urban homeless adults. METHODS: We sampled a community-based probability sample of 534 homeless adults from 41 shelters and meal programs in the Skid Row area of downtown Los Angeles, California. Participants were interviewed and tested for HCV, hepatitis B, and HIV. Outcomes included prevalence, distribution, and correlates of HCV infection; awareness of HCV positivity; and HCV counseling and treatment history. RESULTS: Overall, 26.7% of the sample tested HCV-positive and 4.0% tested HIV-positive. In logistic regression analysis, independent predictors of HCV infection for the total sample included older age, less education, prison history, and single- and multiple-drug injection. Among lifetime drug injectors, independent predictors of HCV infection included older age, prison history, and no history of intranasal cocaine use. Among reported non-injectors, predictors of HCV infection included older age, less education, use of non-injection drugs, and three or more tattoos. Sexual behaviors and snorting or smoking drugs had no independent relationship with HCV infection. Among HCV-infected adults, nearly half (46.1%) were unaware of their infection. CONCLUSIONS: Despite the high prevalence of HCV infection, nearly half of the cases were hidden and few had ever received any HCV-related treatment. While injection drug use was the strongest independent predictor, patterns of injection drug use, non-injection drug use, prison stays, and multiple tattoos were also independent predictors of HCV. Findings suggest that urgent interventions are needed to screen, counsel, and treat urban homeless adults for HCV infection.

Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence.

OBJECTIVE: To compare modafinil to placebo for reducing methamphetamine (MA) use, improving retention, and reducing depressive symptoms and MA cravings. Rates of adverse events and cigarette smoking with modafinil versus placebo were also compared. METHODS: Following a 2-week, non-medication lead-in period, 71 treatment-seeking MA-dependent participants were randomly assigned to modafinil (400mg once daily; N=34) or placebo (once daily; N=37) for 12 weeks under double-blind conditions. Participants attended clinic thrice-weekly to provide urine samples analyzed for MA-metabolite, to complete research assessments, and to receive contingency management and weekly cognitive behavioral therapy (CBT) sessions. RESULTS: There were no statistically significant effects for modafinil on MA use, retention, depressive symptoms, or MA cravings in pre-planned analyses. Outcomes for retention and MA use favored modafinil in a post hoc analysis among participants with low CBT attendance and among participants with baseline high-frequency of MA use (MA use on >18 of past 30 days), but did not reach statistical significance in these small subgroups. Modafinil was safe and well tolerated and did not increase cigarette smoking. CONCLUSIONS: Modafinil was no more effective than placebo at 400mg daily in a general sample of MA users. A post hoc analysis showing a trend favoring modafinil among subgroups with baseline high-frequency MA use and low CBT attendance suggests that further evaluation of modafinil in MA users is warranted.

An exploratory study of long-term neurocognitive outcomes following recovery from opportunistic brain infections in HIV+ adults.

Central nervous system opportunistic infections (CNS-OI) are a significant cause of morbidity and mortality in AIDS. While current interventions are increasingly successful in treating CNS-OI, little information exists regarding long-term behavioral outcomes among survivors. In this exploratory study we examined neurocognitive data among three groups of adults with different AIDS-related CNS-OI: 15 with past cryptococcal meningitis (CM), 8 with toxoplasmosis encephalitis (TE), and 8 with progressive multifocal leukoencephalopathy (PML). A group of 61 individuals with AIDS, but without CNS-OI, was used as a comparison group. A battery of standardized neuropsychological tests assessing a variety of cognitive domains was administered upon entry. Results indicate that individuals with a history of CNS-OI were most impaired on measures of cognitive and psychomotor speed relative to the HIV+ comparison group. Among the CNS-OI groups, individuals with history of TE had the most severe and varied deficits. The results are discussed in relation to what is known about the neuropathological consequences of the various CNS-OIs. While this is the first systematic group study of residual CNS-OI effects on neurocognitive function, future studies employing more participants, perhaps focusing on specific CNS-OIs, will further characterize the long-term outcomes in AIDS-related CNS-OI.

Preclinical and clinical performance of the Efoora test, a rapid test for detection of human immunodeficiency virus-specific antibodies.

Barriers to effective diagnostic testing for human immunodeficiency virus type 1 (HIV-1) infection can be reduced with simple, reliable, and rapid detection methods. Our objective was to determine the accuracy, sensitivity, and specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody detection device. Preclinical studies were performed using seroconversion, cross-reaction, and interference panels, archived clinical specimens, and fresh whole blood. In a multicenter, prospective clinical trial, a four-sample matrix of capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay (EIA) (Abbott Laboratories) licensed by the Food and Drug Administration. Western blot and nucleic acid test supplemental assays were employed to adjudicate discordant samples. Preclinical testing of seroconversion panels showed that antibodies were often detected earlier by the rapid test than by a reference EIA. No significant interference or cross-reactions were observed. Testing of 4,984 archived specimens yielded a sensitivity of 99.2% and a specificity of 99.7%. A prospective multicenter clinical study with 2,954 adult volunteers demonstrated sensitivity and specificity for the Efoora HIV rapid test of 99.8% (95% confidence interval [CI], 99.3 and 99.98%) and 99.0% (95% CI, 98.5 and 99.4%), respectively. Reactive rapid HIV-1 antibody detection was confirmed in 99.6% of those with a known HIV infection (n = 939), 5.2% of those in the high-risk group (n = 1,003), and 0.1% of those in the low-risk group (n = 1,012). For 21 (0.71%) patients, there was discordance between the results of the rapid test and the confirmatory EIA/Western blot tests. We conclude that the Efoora HIV rapid test is a simple, rapid assay for detection of HIV-1 antibodies, with high sensitivity and specificity compared to a standardized HIV-1 EIA.