Maltreatment, psychiatric symptoms and human immunodeficiency virus/sexual transmitted infection risk behavior among youth with alcohol and other drug use problems: A person-centered analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). ^ LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth. ^

Maltreatment, Psychiatric Symptoms and Human Immunodeficiency Virus/Sexual Transmitted Infection Risk Behavior Among Youth with Alcohol and Other Drug Use Problems: A Person-Centered Analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth.

Genomic variation of HIV-1 and its effects on drug resistance and molecular epidemiology analyses

In the first part of this study human immunodeficiency virus type 1 (HIV-1) proviral DNA sequences derived from 201 clones of the C2-V3 env region and the first exon of the tat gene were obtained from six MV-1 infected heterosexual couples. These molecular data were used to confirm the epidemiological relationships. The ability of the molecular data to draw such conclusions was also tested with multiple phylogenetic analyses. The tat region was much more useful in establishing epidemiological relationships than the commonly used C2-V3.^ Subsequently, using nucleotide sequences from the first exon of the Tat gene, we tested the hypothesis that a Florida dentist (a common source) infected five of his patients in the course of dental procedures, against the null hypothesis that the dentist and each individual of the dental group independently acquired the virus within the local community. Multiple phylogenetic analyses demonstrated that the sequences of the five patients were significantly more related to each other than to sequences of the controls. Our results using Tat sequences, combined with envelope sequence data, strongly support a common phylogenetic epidemiological relationship among these five patients.^ A third study is presented, which deals with the effects of genomic variations in drug resistance. HIV-1 reverse transcriptase (RT) mutations were detected in DNA from peripheral blood mononuclear cells from 11 of 12 HIV-infected children after 11-20 months of zidovudine monotherapy. The codon 41/215 mutant combination was associated with general decline in health status. Patients developing the codon 70 mutation tended to have a better health status. ^

Bioinformatic analysis for exploring relationships between genes and gene products

To carry out their specific roles in the cell, genes and gene products often work together in groups, forming many relationships among themselves and with other molecules. Such relationships include physical protein-protein interaction relationships, regulatory relationships, metabolic relationships, genetic relationships, and much more. With advances in science and technology, some high throughput technologies have been developed to simultaneously detect tens of thousands of pairwise protein-protein interactions and protein-DNA interactions. However, the data generated by high throughput methods are prone to noise. Furthermore, the technology itself has its limitations, and cannot detect all kinds of relationships between genes and their products. Thus there is a pressing need to investigate all kinds of relationships and their roles in a living system using bioinformatic approaches, and is a central challenge in Computational Biology and Systems Biology. This dissertation focuses on exploring relationships between genes and gene products using bioinformatic approaches. Specifically, we consider problems related to regulatory relationships, protein-protein interactions, and semantic relationships between genes. A regulatory element is an important pattern or "signal", often located in the promoter of a gene, which is used in the process of turning a gene "on" or "off". Predicting regulatory elements is a key step in exploring the regulatory relationships between genes and gene products. In this dissertation, we consider the problem of improving the prediction of regulatory elements by using comparative genomics data. With regard to protein-protein interactions, we have developed bioinformatics techniques to estimate support for the data on these interactions. While protein-protein interactions and regulatory relationships can be detected by high throughput biological techniques, there is another type of relationship called semantic relationship that cannot be detected by a single technique, but can be inferred using multiple sources of biological data. The contributions of this thesis involved the development and application of a set of bioinformatic approaches that address the challenges mentioned above. These included (i) an EM-based algorithm that improves the prediction of regulatory elements using comparative genomics data, (ii) an approach for estimating the support of protein-protein interaction data, with application to functional annotation of genes, (iii) a novel method for inferring functional network of genes, and (iv) techniques for clustering genes using multi-source data.

Predictors of safer sex behaviors of midlife and older women

Heterosexual transmission of the human immunodeficiency virus (HIV) in midlife and older women is increasing, yet little is known about the safer sex practices of these women. Identification of HIV risk and protective factors necessitates understanding of the influences of individual, interpersonal, and socio-environmental factors on the sexual behaviors of this understudied, at-risk population. The purpose of this study was to determine the influence of self esteem, sensation seeking, self silencing, sexual assertiveness, and HIV-stigma on the safer sex behaviors of women aged 50 and older. ^ This study was guided by the ecological perspective which emphasizes the multilevel factors affecting health behaviors within individual, interpersonal, and socio-environmental contexts. A community-based, ethnically diverse sample of 572 women aged 50 to 93 (M = 63.6 years, SD = 10.5) completed a 128-item anonymous questionnaire. This study used a cross-sectional, correlational research design. The data were analyzed using Pearson correlation coefficients and multiple regression analysis. ^ Results from the regression analysis with the predictors (i.e., ethnicity, education, self esteem, sensation seeking, self silencing, sexual assertiveness, and HIV stigma) indicated the model significantly predicted safer sex behaviors (p < .001). Self silencing (β = -.115, p < .05) was a significant predictor. The lower the self silencing scores, the higher the safer sex behavior scores. Further exploration of the data revealed that the greater the age of the woman, the more likely she is to engage in safer sex behaviors (β = .173, p < .001). While the data showed this model was statistically significant, its practical significance may be limited due to the low proportion of variance explained by age and self silencing. HIV/AIDS prevention interventions that are socially anchored, age-appropriate, and gender-specific are discussed and recommendations for socially meaningful strategies to reduce the number of new cases of HIV/AIDS in midlife and older women are presented. ^

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

Objective: 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.

Substance Use and Sexual Risk Behaviors among Adolescent Detainees

During the past two decades there has been much research conducted on the relationship between the risky sexual behavior practices and substance use among U.S. adolescents. This body of research has documented the fact that substance use and not using condoms are the most important indicators associated with the risk of becoming infected with sexually transmitted diseases (STD) both among adolescents and adults (Florida Department of Public Health, 2004; Malow, Devieux, Jennings, & Lucenko, 2001; McCoy & Inciardi, 1995). Data from those reports and studies indicate that adolescents and adults who use a condom regularly and appropriately are 20 times less likely to contract an STD than those who do not (Pinkerton & Abramson, 1997). However, less empirical evidence exists about the factors that influence adolescent use of condoms, particularly among adolescents who are detained due to their criminal lifestyle. Researchers have found both a high prevalence of STD in addition to early onset of sexual activity without protection among some adolescent groups such as the detainees (D'angelo & DiClemente, 1996) and that adolescents tend to underestimate their risks of acquiring the human immunodeficiency virus (HIV) (Magura, Shapiro, & Kang, 1994). Many adolescents will experiment with alcohol and other drugs. This behavior may compromise their judgment and increase their chances of engaging in risky sex (Rotheram-Borus, 2000). Hence the need for research that investigates the influence that substance use, risky sexual attitudes, knowledge about the transmission of HIV, and both peer and parental approval of condom use have on the use of condoms among both female and male adolescent detainees. Lastly, it is important for additional research to be conducted because adolescent detainees have been identified as being at high risk of becoming infected with an STD (Malow, Rosemberg, & Devieux, 2006). The purpose of this study was to examine the relationship among adolescent substance use, gender, sexual risk attitude, attitude about personal use of condoms, knowledge associated with the transmission of HIV, peer and family approval of condom use, history of sexually transmitted diseases (STD) and the level of condom use in a sample of adolescents housed in a correctional institution. Further details of the explanatory variables, the control variables and their expected relationships can be found in the review of the Literature in Chapter 2. Also, more information about the separate analysis of the research questions is detailed in the Methods section in Chapter 3. Based on the literature detailed in Chapter 2 (e.g., Malow et al., 2006), the current study’s researcher anticipated that adolescents’ higher levels of illicit drug use would be related to higher levels of sexual risk behaviors, as measured by lower levels of condom use, than their counterparts who used no drugs. Similarly, it was hypothesized that positive attitudes toward condom use and higher levels of HIV risk knowledge would be associated with a lower level of risky sexual behaviors along with a higher level of condom use skill. It was further hypothesized that the level of approval perceived from parents and peers regarding condom use was going to be related to adolescents’ safe sex behavior (i.e., condom use). Therefore, it was expected that participants’ perception of a high level of approval to use condoms from peers and parents would be a statistically significant variable in helping explain the condom use within this sample of adolescent detainees.

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.

The Immunomodulatory Role of Alcohol on HIV-Infected Monocyte-Derived Dendritic Cells

Alcohol is known to induce inflammation in the presence of the human immunodeficiency virus (HIV). In our previous studies, we revealed that alcohol induces cannabinoid receptors which play a role in the regulation of inflammatory cytokine production in monocyte-derived dendritic cells (MDDC). However, the ability of alcohol to alter MDDC function during HIV infection has not been clearly elucidated yet. To study the potential impact of alcohol on HIV-infected MDDC (confirmed by p24 ELISA), monocytes were isolated from commercially available buffy coats and cultured for 7 days with GM-CSF and IL-4. MDDC were infected with HIV- 1Ba-L and treated with different concentrations of alcohol (0.1% band 0.2%) for 4-7 days. MDDC phenotype, endocytosis, cytokine production, and ability to transmit HIV to T cells were analyzed. Uninfected CD4+ T cells were co-cultured for 7 days with either infected/treated MDDC or the supernatants from infected/treated MDDC. Inflammatory cytokine arrays were performed using supernatants from HIV-infected MDDC treated with alcohol. Results showed that HIV positive MDDC treated with alcohol had higher levels of infection compared to untreated HIV positive controls. CD4+ T cells exposed to HIV-infected MDDC acquired 100-fold higher levels of p24 compared to CD4+ T cells exposed to only supernatants. CD4+ T cells exposed to HIV-infected and alcohol-treated MDDC had higher levels of infection compared to controls. Cytokine array data show dysregulation of cytokine production by alcohol. In addition, MDDC phenotype and endocytic capacity were altered in the alcohol treated MDDC. Our results indicate a crucial role of MDDC in HIV transmission to T cells and provide insights into the inflammatory role alcohol exerts on dendritic cell function in the context of HIV infection. Supported by the National Institute on Alcohol Abuse and Alcoholism award R00AA021264, the National Institute on Drug Abuse award R01DA034547, and the Institute on NeuroImmune Pharmacology at FIU.