Cognitive performance and the thymus among HIV-infected subjects receiving HAART

Maria J Miguez-Burbano1, John E Lewis2, Jose Moreno3, Joel Fishman41Robert Stempel School of Public Health & School of Medicine, Florida International University, Miami, FL, USA; 2Department of Psychiatry and Behavioral Sciences, 3Department of Medicine, 4Department of Radiology, University of Miami Miller School of Medicine, Miami, FL, USAObjective: To evaluate the impact of alcohol use, which is widespread in human immunodeficiency virus (HIV)+ individuals, on highly active antiretroviral therapy (HAART)-associated immune and cognitive improvements and the relationship between those two responses.Methods: In a case-control longitudinal study, thymic volume, cognition, and immune responses were evaluated at baseline and after 6 months therapy in HIV+ and HIV- controls. Cognitive performance was evaluated using the HIV Dementia Score (HDS) and the California Verbal Learning Test (CVLT).Results: Prior to HAART, thymic volume varied considerably from 2.7 to 29.3 cm3 (11 ± 7.2 cm3). Thymic volume at baseline showed a significantly inverse correlation with the patient’s number of years of drinking (r2 = 0.207; p < 0.01), as well as HDS and the CVLT scores in both HIV-infected (r2 = 0.37, p = 0.03) and noninfected (r2 = 0.8, p = 0.01). HIV-infected individuals with a small thymic volume scored in the demented range, as compared with those with a larger thymus (7 ± 2.7 vs. 12 ± 2.3, p = 0.005). After HAART, light/moderate drinkers exhibited thymus size twice that of heavy drinkers (14.8 ± 10.4 vs. 6.9 ± 3.3 cm3).Conclusions: HAART-associated increases of thymus volume appear to be negatively affected by alcohol consumption and significantly related to their cognitive status. This result could have important clinical implications.Keywords: thymus, CNS, immune, alcoho

Are Serotonin Alterations the Link between Thrombocytopenia and Poor Immune Status among HIV Infected Individuals?

OBJECTIVE: Thrombocytopenia (TCP<150 × 10(3) cells/mm(3)) has emerged as a relevant factor in the clinical course of HIV. However, the mechanisms mediating such observations have not been well characterized, limiting the possibility of creating targeted interventions. Notably, platelets are the storage and transporter system for serotonin and Brain derived neurotrophic factor (BDNF), which recent laboratory studies associated with viral replication and lymphocyte survival. Thus, we posit that (1) TCP will be associated with reduced levels of BDNF and serotonin (2) That these alterations will lead to poor viro-immune responses to antiretroviral therapy. METHODS: To achieve this goal, a total of 400 people living with HIV were consecutively enrolled to characterize the frequency of thrombocytopenia in hazardous and non-hazardous alcohol user populations in the HAART era. Then, participants underwent immune and laboratory assessments, to determine if TCP was associated with alterations in serotonin (5-HT) and brain derived neurotrophic factor (BDNF). RESULTS: The prevalence of thrombocytopenia in this antiretroviral treated cohort was 14%. Rates were significantly higher in the heavy alcohol users, HAU versus the non HAU group (Heavy: 25% versus HAU: 15% versusnon-HAU: 10%). Multivariate model analyses indicated that having TCP, low BDNF levels (<5000 pg/ml), and number of drinks per day were predictors of serotonin levels. PLWH with TCP had about 2-fold lower PPP-BDNFlevels (5037.4 ± 381 vs. 9137.5 ± 7062 pg/ml p=0.0001). Other significant predictors of BDNF levels at the last visit included receiving selective serotonin reuptake inhibitors and PPP serotonin levels. Multivariate analyses also confirmed that altered serotonin levels were associated withhigh viral loadsboth low CD4 cell counts. CONCLUSIONS: Thrombocytopenia is a relatively frequent complication of HIV, andis particularly prevalent among hazardous alcohol users (HAU). These findings suggest that TCP is associated with altered levels of BDNF and serotonin, suggesting that they may be the bridge linking TCP and poor viro-immune responses observed in this group. These results could have important clinical and therapeutic implications

Alcohol, Brain Derived Neurotrophic Factor and Obesity among People Living with HIV

Introduction In an expanding HAART era, obesity has become a health problem among persons living with HIV (PLWH). Whereas the rising level of obesity has been largely attributed to poor nutrition and exercise habits, differences in biological factors may explain why some individuals gain more weight than others. Thus, our main goal is to prospectively determine in PLWH whether plasma brain-derived neurotrophic factor (BDNF), and hazardous alcohol use (HAU), two overlooked but highly prevalent conditions among PLWH, correlate with an adverse anthropometric profile. Also to test whether these relationships varied in men and women Methods The Platelets mediating Alcohol and HIV Damage Study (PADS) is an ongoing multiethnic study of 400 PLWH receiving regular medical care in South Florida (37% females and 63% males). Semi-annual visits consisted of a medical exam, including anthropometrics to assess both general (body mass index: BMI) and central obesity (waist and hip circumferences). Participants also completed health history questionnaires, and provided a fasting blood sample to obtain BDNF and immune and biochemical assessments. Results A sizable proportion of participants met the National Institutes of Health definition of overweight (BMI = 25?29.9 kg/m2; 26%) and obese (BMI ? 30 kg/m2; 35%). Women were more likely to be obese than men (OR=4.9, 95% CI=2.9?8.2, p=0.0001). Compared to men, women also exhibited the highest mean plasma BDNF levels (9,959 ± 6,578 vs. 7,470 ± 6,068 pg/ml, p=0.0001). Additional analyses indicated that HAU, particularly heavy drinkers, had the smallest waist and hip circumferences if they were males, but the opposite if they were females. High BDNF levels were positively correlated with BMI. Linear regression analysis revealed that gender, BDNF, and HAU were the best predictors of BMI. Conclusion In summary, our findings offer novel insights into the relationships between BDNF, and alcohol use among overweight and obese PLWH. Our results also suggest that these relationships may be inherently different by gender

Mood Disorders and BDNF Relationship with Alcohol Drinking Trajectories among PLWH Receiving Care

Background Despite the excessive rates of Hazardous Alcohol Use (HAU) among people living with HIV (PLWH), although largely speculated, psychological and physiological components associated with HAU, has not been actively measured. Therefore, the present study was geared toward determining: 1) the rates of mood disorders and its relationship with HAU, and 2) to assess the impact of Brain Derived Neurotrophic Factor (BDNF), a well-known regulator of alcohol and mood disorders. Methods For this study, participants of the longitudinal PADS Study n=400, were followed over time. Alcohol use (Alcohol Use Disorders Identification Test ?AUDIT- and the Alcohol Dependence Scale ?ADS) and moods (depression, anxiety, and stress) were assessed repeatedly. Results A cluster analyses shows three distinctive trajectories. The first one, revealed a group with increased drinking (Cluster 1: n=140), constant alcohol intake (Cluster 2: n = 60), and one with decreased consumption (Cluster 3: n =120). Analyses discovered higher AUDIT scores across the clusters with Cluster 1 being followed by Clusters 2 and 3 (1: 14.5 ± 8 vs. 2=8.7 ± 7.5 vs. 3= 6.6 ± 4.2, p = 0.001). Women in Clusters 1 and 2 had higher levels of stress (1:21 ± 7.5; 2:19.3 ± 7) and lower BDNF levels (7904 ± 1248 pg/ml and 10405 ± 909 pg/mL) than their counterparts in Cluster 3 (PSS: 3: 16.6 ±5, p = 0.02 BDNF: 10828 ± 1127 pg/mL, p = 0.08). Men in Cluster 1 differed in terms of stress (19.8 ± 7 vs. 21 ± 7.5 score) and BDNF levels (Cluster 1: 5204 ± 818 vs. Cluster 2: 7656 ± 843 pg/ml, p = 0.002) but not in the number of years living with HIV. The proportion of subjects with multiple mood comorbidities was disturbingly higher (26%), and all were members of Cluster 1. Multiple logistic regression analyses indicated that participants reporting high relative to low levels of perceived stress, dual mood comorbidity, altered BDNF levels and low income increased the likelihood of being a member of Cluster 1. Conclusion This study found that stress and overlaying psychiatric comorbidities are linked with persistent alcohol use. Findings suggest that BDNF and social support seems to be a logical target as it seems to be the bridge linking mood disorders and alcohol consumption

HIV treatment in drug abusers: impact of alcohol use

Studies of alcohol use in HIV-1 infected patients have resulted in conflicting and limited information regarding prevalence, as well as impact on HIV replication, disease progression and response to antiretroviral therapy. Alcohol, drug abuse and past medical information, including antiretroviral treatment, were obtained using research questionnaires and medical chart review in 220 HIV-1 infected drug users. A physical examination was conducted and blood was drawn to evaluate immune measures and nutritional status. Heavy alcohol consumption, defined as daily or 3 - 4 times per/week, was reported in 63% of the cohort. Men (odds ratio (OR) = 2.6, 95% CI 1.13 - 5.99, p = 0.013), and participants between 35 and 45 years of age were three times more likely to be heavy alcohol users (p = 0.006 and 0.0009, respectively). Low serum albumin levels were more evident in heavy alcohol users than non-drinkers (p = 0.003). Heavy alcohol users receiving antiretroviral therapy were twice as likely to have CD4 counts below 500 than light or non-drinkers (95% CI, 1 - 5.5, p = 0.03), and highly active antiretroviral therapy (HAART)-treated heavy alcohol users were four times less likely to achieve a positive virological response (95% CI, 1.2 - 17, p = 0.04). Alcohol consumption is prevalent in our HIV-1 infected drug user cohort and significantly impacts both immunological and virological response to HAART treatment

Impact of a Selenium Chemoprevention Clinical Trial on Hospital Admissions of HIV-Infected Participants

Purpose: To evaluate the impact of selenium chemoprevention (200μg/day) on hospitalizations in HIV-positive individuals. Method: Data were obtained from 186 HIV+ men and women participating in a randomized, double-blind, placebo-controlled selenium clinical trial (1998-2000). Supplements were dispensed monthly, and clinical evaluations were conducted every 6 months. Inpatient hospitalizations, hospitalization costs, and rates of hospitalization were determined 2 years before and during the trial. Results: At enrollment, no significant differences in CD4 cell counts or viral burden were observed between the two study arms. Fewer placebo-treated participants were using antiretrovirals (p < .05). The total number of hospitalizations declined from 157 before the trial to 103 during the 2 year study. A marked decrease in total admission rates (RR = 0.38; p = .002) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed (p = .01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p = .001). In the final analyses, selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization (p = .001). Conclusion: Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1--infected patients

Impact of tobacco use on the development of opportunistic respiratory infections in HIV seropositive patients on antiretroviral therapy

The increased risk of developing lung diseases in cigarette smokers has been well recognized. The association between smoking and the risk of developing pulmonary infections in HIV-1-infected patients, however, which has not been established, was evaluated in the present study. Twenty-seven cases with lower respiratory infections (15 Pneumocystis carinii pneumonia (PCP), 12 TB cases) were compared with 27 age, gender, socio-economic and HIV status-matched patients, without history of respiratory diseases. Medical history and physical examinations were obtained every 6 months. Blood was drawn for CD4 and viral load measurements. A substantial number of HIV + smokers who developed PCP (one-third) had been on highly active retroviral therapy (HAART) for more than 6 months and prophylaxis had been discontinued. Multivariate analyses indicated that in HIV-infected people, after controlling for HIV status and antiretrovirals, cigarette smoking doubled the risk for developing PCP (p = 0.01). Multivariate analyses demonstrated that long-term smoking also increased the risk (2 x) of developing tuberculosis (p = 0.04). Moreover, daily tobacco use seemed to attenuate by 40% the immune and virological response to antiretroviral therapies. These findings indicate that tobacco use significantly increases the risk of pulmonary diseases in HIV infected subjects and has a potential deleterious impact on antiretroviral treatment

Continued High Risk Behaviors in HIV Infected Drug Abusers

To characterize current risk behaviors of HIV drug abusers in the highly active antiretroviral therapy (HAART) era, socio-demo-graphic, medical and behavioral information were obtained and immune measurements determined. High-risk sexual practices were prevalent. Participants diagnosed before 1995 were 6 times more likely to have unprotected sex with HIV+ partners (p = 0.05) and 11 times more likely to use contaminated needles (p = 0.05) than participants with later diagnosis. Consistent condom use was reported by only 7% of the cohort. Many (43%) of the participants reported multiple HIV+ and HIV-concurrent partners. Most (65%), particularly women (OR = 3, p = 0.02), did so for drugs or money. Despite detectable viral loads, 36% reported unprotected anal sex. Antiretroviral-treated men, compared to non-treated, tended to have unprotected anal sex (OR = 2, p = 0.07). The continued high-risk behaviors of HIV drug users, particularly those diagnosed before 1995 and/or on antiretroviral therapy, indicates an urgent need for new public health strategies

Increased risk of Pneumocystis carinii and community-acquired pneumonia with tobacco use in HIV disease

Tobacco smoking-related diseases continue to be of great health concern for the public, in general, and may be particularly deleterious for immunosuppressed HIV-positive individuals, who exhibit widespread tobacco use. A total of 521 HIV-infected subjects consecutively admitted to Jackson Memorial Hospital between 2001–2002 were enrolled in the study. Research data included a medical history, details of tobacco and illicit drug use and complete computerized hospital information. Blood was drawn to obtain T lymphocyte profiles and viral load levels. Statistical analysis methods included Pearson, Student's t- and Chi-square tests and SAS Proc CATMOD. Tobacco use was prevalent, with 65% of the 521 HIV-positive hospitalized patients being current smokers. Overall, current tobacco users reported smoking an average of 15 ± 13 cigarettes per day for an average of 15 ± 14 years, with 40% smoking more than one pack per day. Pulmonary infections accounted for 49% of the total hospital admissions: 52% bacterial pneumonias, 24% Pneumocystis carinii pneumonia (PCP), 12% non-tuberculous mycobacterial diseases (NTM), 11% tuberculosis and 1% bronchitis. Many of the respiratory patients (46%) had been on highly active antiretroviral therapy (HAART) for over six months and 42% had received PCP and/or NTM prophylaxis. After matching the cases by HAART and CDC stage, the hazardous risk of being hospitalized with a respiratory infection was significantly higher for smokers than non-smokers (95% CI 1.33–2.83; p = 0.003). Respiratory infections were noted in (37%) of the HAART-treated patients, and most (67%) occurred in smokers. CATMOD analyses controlling for HAART, viral load and CD4, indicated that HIV-infected smokers were three times more likely to be hospitalized with PCP and twice as likely to be hospitalized with community-acquired pneumonia than non-smokers, with increased risk related to the number of cigarettes/day in a dose-dependent manner. Tobacco use, which is widespread among HIV-infected subjects, increases the risk of pulmonary diseases, particularly PCP and CAP, two respiratory infections with high prevalence and morbidity risks even in the era of HAART