The relationship of thymulin activity, immune parameters of HIV disease progression and substance use in a cohort of HIV seropositive alcohol and drug users

Zinc is essential for the activity of thymulin, a thymic hormone involved in T-lymphocyte differentiation and activation. Zinc deficiency is widespread in populations with HIV infection, and HIV+ drug users are particularly susceptible to zinc deficiency and immune suppression. This dissertation explored the relationship of zinc-bound active thymulin to plasma zinc, CD4+ and CD8+ cell count, the CD4+/CD8+ ratio, and drug use in HIV-infected drug users. Zinc-bound active thymulin was assessed in plasma of HIV+ drug users who were participating in a 30 month zinc supplementation trial. Plasma from 80 participants at the 12 month visit, and 40 of these same participants, randomly selected, at the baseline visit were assessed for zinc-bound active thymulin levels using a modification of the rosette inhibition assay. Thymulin activity was directly associated with CD4+ cell count (β = 0.127, p = 0.002) and inversely associated with cocaine use (β = −0.908, p = 0.026; R2 = 0.188, p = 0.019) independent of HIV viral load, age, gender and antiretroviral use. An increase in thymulin activity was 1.4 times more likely when CD4+ cell count increased (OR = 1.402, 95%CI: 1.006–1.956), independent of change in viral load, antiretroviral use, and age. Participants who used cocaine consistently, were 7.6 times less likely to have an increase in thymulin activity (OR = 0.133, 95%CI: 0.017–1.061). There was a direct correlation between change in plasma zinc and change in zinc-bound active thymulin (r = 0.243, p = 0.13). Analysis of CD4+ cell count decline in 222 participants in the zinc supplementation trial across the 30 months showed that both crack cocaine use and heavy alcohol use accelerated CD4+ cell count decline. Thymulin activity is directly associated with HIV disease progression, measured by CD4+ cell count, and is depressed with cocaine use independent of antiretroviral use and HIV viral load. Cocaine and heavy alcohol accelerate CD4+ cell count decline. The effect of cocaine on thymic output requires further evaluation as a mechanism for the association of cocaine use with faster HIV disease progression.

Overweight/Obesity and HIV Disease Progression in HIV+ Adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.

Overweight/obesity and HIV disease progression in HIV+ adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m 2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). ^ At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. ^ FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. ^ Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. ^ In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.^

An evaluation of depression, self-efficacy, satisfaction with life and perceived access to medical care across stages of HIV infection

This survey was designed to identify the incidence and scope of depression, satisfaction with life, self-efficacy and perceived access to medical care for those who are infected with the HIV virus. It also determined whether or not factors such as sexual orientation, ethnicity and socioeconomic status are intervening variables with respect to mental health issues. Subjects were recruited through a purposive sample from South Florida. A total of 871 surveys were used in the analysis. The overall response rate was nearly 90%. The incidence of depression was found to be higher than 75% across all stages of HIV infection. Furthermore, the incidence of depression increased as HIV disease progressed. Satisfaction with life and for the most part, self efficacy were found to decrease slightly as HIV disease progressed. Significant variance in depression, life satisfaction and self efficacy were found across stages of HIV infection. No significant differences between groups that were HIV infected were found for depression, life satisfaction and self efficacy. The severity of depression was found to vary significantly with self efficacy, life satisfaction and access to medical care but not with socioeconomic status. Life satisfaction was found to vary significantly with socioeconomic status, depression and self efficacy but not with access to medical care. Self-efficacy was found to vary significantly with socioeconomic status, depression and life satisfaction but not with access to medical care. Gender and ethnicity were not found to be significant precedent variables in depression for HIV infected individuals. Sexual orientation was found to be a significant precedent variable for depression, life satisfaction and self efficacy.

Impact of nutrition education on knowledge and eating patterns in HIV-infected individuals

Acquired Immune Deficiency Syndrome (AIDS) and impaired or threatened nutritional status seem to be closely related. It is now known that AIDS results in many nutritional disorders including anorexia, vomiting, protein-energy malnutrition (PEM), nutrient deficiencies, and gastrointestinal, renal, and hepatic dysfunction (1-7, 8). Reversibly, nutritional status may also have an impact on the development of AIDS among HIV-infected people. Not all individuals who have tested antibody positive for the Human Immunodeficiency Virus (HIV) have developed AIDS or have even shown clinical symptoms (9, 10). A poor nutritional status, especially PEM, has a depressing effect on immunity which may predispose an individual to infection (11). It has been proposed that a qualitatively or quantitatively deficient diet could be among the factors precipitating the transition from HIV-positive to AIDS (12, 13). The interrelationship between nutrition and AIDS reveals the importance of having a multidisciplinary health care team approach to treatment (11), including having a registered dietitian on the medical team. With regards to alimentation, the main responsibility of a dietitian is to inform the public concerning sound nutritional practices and encourage healthy food habits (14). In individuals with inadequate nutritional behavior, a positive, long-term change has been seen when nutrition education tailored to specific physiological and emotional needs was provided along with psychological support through counseling (14). This has been the case for patients with various illnesses and may also be true in AIDS patients as well. Nutritional education specifically tailored for each AIDS patient could benefit the patient by improving the quality of life and preventing or minimizing weight loss and malnutrition (15-17). Also, it may influence the progression of the disease by delaying the onset of the most severe symptoms and increasing the efficacy of medical treatment (18, 19). Several studies have contributed to a dietary rationale for nutritional intervention in HIV-infected and AIDS patients (2, 4, 20-25). Prospective, randomized clinical research in AIDS patients have not yet been published to support this dietary rationale; however, isolated case reports show its suitability (3). Furthermore, only nutrition intervention as applied by a medical team in an institution or hospital has been evaluated. Research is lacking concerning the evaluation of nutritional education of either non-institutionalized or hospitalized groups of persons who are managing their own food choice and intake. This study compares nutrition knowledge and food intakes in HIV-infected individuals prior to and following nutrition education. It was anticipated that education would increase the knowledge of nutritional care of AIDS patients and lead to better implementation of nutrition education programs.

Maternal-Fetal Attachment and Health Behaviors among Women with HIV/AIDS

Background: Mothers with HIV often face personal and environmental risks for poor maternal health behaviors and infant neglect, even when HIV transmission to the infant was prevented. Maternal-fetal attachment (MFA), the pre-birth relationship of a woman with her fetus, may be the precursor to maternal caregiving. Using the strengths perspective in social work, which embeds MFA within a socio-ecological conceptual framework, it is hypothesized that high levels of maternal-fetal attachment may protect mothers and infants against poor maternal health behaviors. Objective: To assess whether MFA together with history of substance use, living marital status, planned pregnancy status, and timing of HIV diagnosis predict three desirable maternal health behaviors (pregnancy care, adherence to prenatal antiretroviral therapy–ART, and infant’s screening clinic care) among pregnant women with HIV/AIDS. Method: Prospective observation and hypothesis-testing multivariate analyses. Over 17 consecutive months, all eligible English- or Spanish-speaking pregnant women with HIV ( n = 110) were approached in the principal obstetric and screening clinics in Miami-Dade County, Florida at 24 weeks’ gestation; 82 agreed to enroll. During three data collection periods from enrollment until 16 weeks after childbirth (range: 16 to 32 weeks), participants reported on socio-demographic and predictor variables, MFA, and pregnancy care. Measures of adherence to ART and infant care were extracted from medical records. Findings: Sociodemographic, pregnancy, and HIV disease characteristics in this sample suggest changes in the makeup of HIV-infected pregnant women parallel to the evolution of the HIV epidemic in the USA over the past two decades. The MFA model predicted maternal health behaviors for pregnancy care (R2 = .37), with MFA, marital living status, and planned pregnancy status independently contributing ( = .50, = .28, = .23, respectively). It did not predict adherence to ART medication or infant care. Relevance: These findings provide the first focused evidence of the protective role of MFA against poor maternal health behaviors among pregnant women with HIV, in the presence of adverse life circumstances. Social desirability biases in some self-report measures may limit the findings. Suggestions are made for orienting future inquiry on maternal health behaviors during childbirth toward relationship and protection.

Effect of the Supplemental Nutrition Assistance Program (SNAP) and nutrition education on nutrition and health outcomes of HIV+ individuals

Factors associated with and barriers to participation in Supplemental Nutrition Assistance Program (SNAP) and the effect participation has on food security, nutrition status, disease status and quality of life was investigated in a cross-sectional study including 175 HIV infected individuals. In addition, the effect of a targeted nutrition education on nutrition knowledge, readiness to dietary behavior change, nutrition status, disease status and quality of life was also investigated among a subset of the population (N = 45) in a randomized clinical control trial. ^ SNAP participation rate was 70.3%, similar to the State of Florida and national participation rates. SNAP participation was positively and independently associated with being born in the US (P < 0.001), having monthly income less than $1000 (P = 0.006), and receiving antiretroviral treatment (P < 0.001). Participation barriers include denial of participation by program, recent incarceration, living in a shelter where participation is not allowed and unawareness of eligibility status. In regression analyses, SNAP participation was not significantly associated with improved food security, nutrition status, disease status and health related quality of life (HRQOL). Over half (56%) of the population experienced food insecurity and had inadequate intakes of half of the nutrients assessed. Illicit drug, alcohol and cigarette use were high in this population (31%, 55% and 63% respectively), and affected food security, nutrients intake, disease status and HRQOL. The nutrition education intervention resulted in a trend towards improvements nutrition knowledge, self-efficacy, and readiness to change without impacting nutrition status, disease state and quality of life. ^ Food insecurity and other nutrition related issues, with implications for treatment, management and cost of HIV disease, continue to plague infected individuals living in poverty. More resources, including food and nutrition programs, specifically targeted towards this population are needed to address these issues.^

The influence of gene environment interaction on the risk of cognitive impairment: Reducing sexual risk behaviors and alcohol use in HIV-infected adults

Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. ^ A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p^

The Influence of Gene Environment Interaction on the Risk of Cognitive Impairment: Reducing Sexual Risk Behaviors and Alcohol Use in HIV-infected Adults

Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p

Effect of the Supplemental Nutrition Assistance Program (SNAP) and Nutrition Education on Nutrition and Health Outcomes of HIV+ Individuals

Factors associated with and barriers to participation in Supplemental Nutrition Assistance Program (SNAP) and the effect participation has on food security, nutrition status, disease status and quality of life was investigated in a cross-sectional study including 175 HIV infected individuals. In addition, the effect of a targeted nutrition education on nutrition knowledge, readiness to dietary behavior change, nutrition status, disease status and quality of life was also investigated among a subset of the population (N = 45) in a randomized clinical control trial. SNAP participation rate was 70.3%, similar to the State of Florida and national participation rates. SNAP participation was positively and independently associated with being born in the US (P < 0.001), having monthly income less than $1000 (P = 0.006), and receiving antiretroviral treatment (P < 0.001). Participation barriers include denial of participation by program, recent incarceration, living in a shelter where participation is not allowed and unawareness of eligibility status. In regression analyses, SNAP participation was not significantly associated with improved food security, nutrition status, disease status and health related quality of life (HRQOL). Over half (56%) of the population experienced food insecurity and had inadequate intakes of half of the nutrients assessed. Illicit drug, alcohol and cigarette use were high in this population (31%, 55% and 63% respectively), and affected food security, nutrients intake, disease status and HRQOL. The nutrition education intervention resulted in a trend towards improvements nutrition knowledge, self-efficacy, and readiness to change without impacting nutrition status, disease state and quality of life. Food insecurity and other nutrition related issues, with implications for treatment, management and cost of HIV disease, continue to plague infected individuals living in poverty. More resources, including food and nutrition programs, specifically targeted towards this population are needed to address these issues.

The role of community college faculty in teaching and learning for sustainable development

The purpose of this study was to explore the attitudes, beliefs, and practices of community college professors regarding education for sustainable development (ESD). In-depth interviews with 14 professors from different disciplines were conducted. The participants taught at Miami Dade College, Florida, a Talloires Declaration signatory since 2006, and all had attended Green Studies professional development workshops. Written documents such as assignments and samples of student work were used for triangulation. The annual report of the college’s Earth Ethics Institute and its Web site served as additional sources. The interviews were recorded, transcribed, and analyzed for common themes. The Talloires Declaration’s 10-point action plan and the key characteristics of ESD (UN DESD, 2006) served as the conceptual framework. The study found that the professors considered ESD an essential issue. The majority discussed the economic and social aspects of ESD; however, the environmental aspect was mentioned most frequently. The professors’ conceptualizations of ESD were influenced by their experiences and evidenced by the metaphors they used. Although their engagement with ESD differed, the professors expressed optimism toward ESD related teaching and learning. They regarded ESD as compatible with their subjects, and most had already been infusing sustainability into their courses or planned to do so. Additionally, the participants’ teaching practices reflected many of the characteristics of ESD. Even though the professors considered ESD challenging, they believed that they could make contributions to the college’s effort. The metaphor of “Planting a Seed” was frequently used to describe this holistic approach. The study also found that many professors regarded interpersonal relationships and communication significant factors for the advancement of ESD. The participants described several challenges to integrating ESD at their college. These related to time constraints, density of curriculum, institutional size and fragmentation, dearth of administrative support and incentives, students’ lack of academic preparation and sustainability awareness, students’ inability to focus on ESD because of personal, social, or economic circumstances, and professors’ frustration about a divisive atmosphere as a result of their engagement with sustainability. Despite these obstacles, the professors believed that ESD could be successfully woven into the community college experience.