UMD Theses and Dissertations

Permanent URI for this collectionhttp://hdl.handle.net/1903/3

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    The effects of HIV criminalization laws (and their enforcement) on HIV risk among Black and Hispanic populations
    (2022) Keralis, Jessica Maciel; Nguyen, Quynh C; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Background: In the U.S., 25 states have laws that explicitly criminalize the transmission or exposure of HIV. This study, grounded in Nancy Krieger's ecosocial theory, estimated the association between HIV criminalization laws and state- (Aim 1) and county-level (Aim 2) HIV incidence rates, as well as individual HIV testing history (Aim 3), and assessed effect modification by overpolicing, using incarceration rates as a proxy. Methods: The study uses data from state- and county-level HIV incidence data from AIDSVu (2010-2019), incarceration data from the Vera Institute of Justice (2010-2018), and HIV testing data from BRFSS (2016-2019). For Aim 1, a longitudinal analysis was conducted using multivariate marginal Poisson GEE models to estimate rate ratios. For Aim 2, count-rate hierarchical (multilevel) models were fitted to estimate rate ratios. For Aim 3, logistic regression models were fitted to estimate odds ratios. Results: The presence of a state HIV testing law was associated with a higher state HIV incidence in the general and Hispanic populations (aRR=1.48 and 1.68, respectively), but higher incarceration at the state level did not significantly modify the relationship between the law and HIV incidence. At the county level, being in a state with an HIV-specific criminalization statute was associated with a higher county-wide HIV incidence rate for all three populations (aRR=1.14, 1.30, and 1.32 for the general, Black, and Hispanic populations, respectively). Unlike the state-level analysis, this association was attenuated by a higher jailed population rate for the general and Black populations. The effect modification was statistically significant for the general population (p=0.01) and marginally significant for the Black population (p=0.06). Finally, the presence of a state HIV testing law (aOR=1.06) was associated with a greater likelihood of HIV testing history in the general population. However, in HIV criminalization states, heavier policing negatively modified the effect of the law on the likelihood of having ever received an HIV test (p<0.01). Public health implications: This study contributes to a gap in the literature by using recent data to estimate the association of HIV criminalization laws and their enforcement with HIV incidence rates and HIV testing behavior.
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    A Qualitative Examination of the Barriers and Facilitators of Pre-Exposure Prophylaxis (PrEP) Uptake Among Heterosexual HIV Serodiscordant Couples
    (2022) Mathews, Ronneal; Mittal, Mona; Family Studies; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    It is estimated that there are 140,000 heterosexual serodiscordant couples in the United States. Given the considerable number of these couples and the high risk of HIV acquisition among non-infected partners, it is important to focus prevention methods on programs and interventions that target transmission of HIV infection among serodiscordant heterosexual couples. Currently, we understand little about factors that influence these couples to use pre-exposure prophylaxis (PrEP). According to the CDC, this population is one of the highest risk groups, therefore, understanding the factors that influence them to use PrEP as a strategy in their HIV prevention regimen is an important step in preventing new HIV cases among this population. This study was a qualitative analysis that explored potential motivators and inhibitors for PrEP among heterosexual HIV serodiscordant couples. Secondary data from 26 qualitative interviews of HIV serodiscordant couples (N = 52 individuals) was examined to determine the factors that influenced the decision to use PrEP. Overall, there were five overarching themes from the Health Belief Model that manifested in all participant interviews. Perceived threat, perceived barriers (concerns about side effects, fear/anxiety about taking medication, indifference about HIV transmission), perceived benefits, cues to action (partner protection, PrEP use as condom replacement, PrEP use due to concerns about condom efficacy), and relational efficacy emerged as the most salient themes that determined whether couples chose to use PrEP as an HIV prevention method. Two constructs from the Theory of Gender and Power, sexual division of power and cathexis also emerged as relevant factors that influenced the decision to use PrEP in these couples. Findings from this study indicate that practitioners need to consider the motivators and barriers to PrEP uptake, and critically examine how power dynamics impact the decision to use PrEP. There is a need for the development of couples-based interventions to encourage PrEP uptake and adherence in mixed status couples.
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    Exploring Psychosocial and Structural Syndemic Effects as Predictors for HIV-Related Outcomes among Black Women
    (2022) Watson, Lakeshia; Dyer, Typhanye; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Black women continue to be disproportionately affected by HIV with marked disparities in HIV incidence, prevalence, and care outcomes. There is a critical need to explore the role of psychosocial and structural factors and the negative impact of these factors on HIV-related outcomes, including HIV risk behaviors, HIV medication adherence, and healthcare utilization. This research uses the syndemic theory to measure the effects of both psychosocial and structural syndemics on HIV-related outcomes among Black women. Syndemic theory is a theoretical framework, which posits there are multiple, overlapping factors that form a cumulative and synergistic effect on HIV disease burden. The substance abuse, violence and AIDS (SAVA) syndemic, clustering effects of substance use, intimate partner abuse, and HIV/AIDS, have been applied in studies exploring HIV outcomes among women; however, the SAVA syndemic framework does not include additional psychosocial and structural factors such as food insecurity, housing instability, incarceration, post -traumatic stress disorder, and depression to better understand the syndemic profiles of Black women. Using study data from the HIV Prevention Trials Network 061 Women’s Seroincidence study and the Women’s Interagency HIV Study, we tested whether a cumulative syndemic of psychosocial and structural factors contributed to sexual risk behaviors and HIV care outcomes. The studies will assess three parameterizations of syndemic factors: cumulative syndemic index, syndemic group indices reflecting the level of influence (psychosocial, participant-level, and neighborhood), and number of syndemic groups (0, 1, 2, or 3). We also tested whether HIV status modified the relationships between a cumulative syndemic of psychosocial and structural factors and sexual risk behaviors. In study 1, a higher syndemic score was significantly associated with increased prevalence of unknown HIV status of last male sex partner (aPR = 1.07, 95% CI: 1.04-1.10), engaging in exchange sex (aPR = 1.17, 95% CI: 1.14-1.20), and having multiple sex partners (aPR = 1.07, 95% CI: 1.06-1.09) among a sample of 1,347 Black women. In study 2, generalized linear mixed models found that being in two syndemic groups was associated with increased odds of reporting unknown HIV status of last male sex partners (aOR=3.04, 95% CI: 1.24-7.44) and having multiple sex partners (aOR=4.29, 95% CI: 1.81-10.18) among 1,364 Black women living with and without HIV across twelve follow-up visits. We also found that being in all three syndemic groups was associated with increased odds of reporting inconsistent condom use (aOR= 2.15, 95% CI: 1.28-3.61), unknown HIV status of last male sex partners (aOR=5.26, 95% CI: 1.94-14.25), and having multiple sex partners (aOR=7.47, 95% CI: 2.85-19.58). Among a total of 969 Black women living with HIV in study 3, a higher cumulative syndemic score and a higher neighborhood-level structural syndemic group score was associated with increased odds of reporting sub-optimal HIV medication adherence (aOR=1.04, 95% CI: 1.01-1.06 and 1.08, respectively). Black women in all three syndemic groups had increased odds of reporting sub-optimal HIV medication adherence (OR=2.88, 95% CI: 1.32-6.29) and missed HIV appointments (OR=3.39, 95% CI: 1.06-10.92). Results from these studies highlight the evidence of psychosocial and structural syndemic effects on multiple HIV risk and care outcomes among Black women.
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    EFFECTS OF INTERSECTING STIGMAS ON HIV AND ALCOHOL-RELATED HEALTH BEHAVIORS
    (2021) Regenauer, Kristen S; Magidson, Jessica F; Psychology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    South Africa (SA) has a high burden of HIV and problematic alcohol use. However, associations between HIV stigma and alcohol-outcomes, and alcohol stigma and HIV-outcomes are largely unknown. Further, limited research has examined the role of avoidance in these associations. Therefore, as part of a larger clinical trial, we explored these associations among people living with HIV (PLWH) and problem drinking in SA (N=64). Patients had blood drawn for biomarker-verified measures of outcome variables, and completed self-report measures for all variables. A significant interaction was found between internalized HIV stigma and avoidance in predicting self-report problematic alcohol use (b(SE)=.24(.09), p=.01) such that at low levels of avoidance, higher HIV stigma was associated with less problematic alcohol use (b(SE)=-1.92(.85), p=.03). A matching nonsignificant pattern was observed for biomarker-verified alcohol consumption, suggesting that the relationship between internalized HIV stigma and problematic alcohol use may be moderated by avoidance.
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    Effects of the 2014-2016 Ebola Epidemic on Infectious Disease Prevention in Guinea
    (2021) Callaway, Julia; Dyer, Typhanye V; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    From 2014-2016, Ebola ravaged the three West African countries of Guinea, Sierra Leone, and Liberia. There were more than 28,000 cases and 11,000 deaths, with more than 10,600 additional deaths due to other medical conditions. We aimed to examine how utilization of infectious disease prevention services changed in Guinea over the course of the Ebola epidemic, using Andersen’s model of healthcare utilization as a theoretical framework. The specific aims of this study were: 1) to examine differences in measles vaccination rates among children ages 12-35 months before and after the Ebola epidemic by wealth quintile; 2) to estimate mosquito net possession at two time points post-epidemic compared to pre-epidemic among households with at least one child under five, nationally and regionally; and 3) to quantify how much of the association between exposure to the Ebola epidemic and HIV testing prevalence can be explained by changes in urban/rural residence rates among adults in Guinea. The studies use data from the 2012 and 2018 Guinea DHS, and the 2016 MICS. Studies 1 and 2 use quasi-Poisson regression models to estimate prevalence ratios, and study 3 uses log-binomial regression models in a mediation analysis. In study 1 (n = 2,573 children ages 12-35 months), the poorest children were 54% (95% CI = 58%-67%) as likely to be vaccinated for measles in 2018 compared to 2012, and the wealthiest children were 78% (95% CI = 69%-90%) as likely. In study 2 (n = 14,756 households with at least one child under five), mosquito net possession in 2016 was 72% (95% CI = 56%-90%) higher and in 2018 was 12% (95% CI = 8%-15%) higher than in 2012. In study 3 (n = 27,809 adults), of the 4.59% (95% CI = 4%-6%) increase in the log-likelihood of ever having been tested for HIV due to being in the 2018 cohort, an estimated 0.269% of the effect (95% CI = 0.04%-1%) could be attributed to differences in urban/rural residence. Understanding these changes gives a more complete picture of the effects of epidemics on infectious disease prevention and can help public health officials plan for future epidemics.
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    CHEMOENZYMATIC MODULATION OF GLYCOPEPTIDE ANTIGENS AS TARGETS FOR HIV VACCINE DISCOVERY AND LIVER CANCER DIAGNOSIS
    (2020) Zhang, Roushu; Wang, Lai-Xi; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Glycosylation is a critical post-translational modification of proteins. Viral pathogens use the host glycosylation machinery to facilitate their entry and hide them from the host immune recognition. Moreover, changing the glycosylation pattern is often related to the development of diseases, such as the emergence of carcinomas. Therefore, carbohydrates are attractive targets for various infectious diseases and pathogenic disorders. Nonetheless, as the synthesis of glycans is not template-driven, glycoforms obtained from natural resources are heterogeneous. We address this issue by employing glycosidase inhibitors to modulate protein glycosylation during expression, and also by chemoenzymatic glycan remodeling of glycopeptide antigens. Three projects related to this topic are described herein.In the first project, a series of glycan-defined HIV-gp120-derived glycoprotein immunogens were expressed and engineered. We successfully demonstrated the glycan-dependency of a variety of HIV-targeting broadly neutralizing antibodies (bnAbs). Our immunogens bearing the high-mannose glycosylation have adequate antigenicity towards the bnAbs evaluated, rendering these immunogens promising vaccine candidates for HIV/AIDS. The second project focused on designing novel glycopeptide immunogens for raising glycan-specific antibodies to detect the early stage of liver cancer. Here we chose the fucosylated alpha-fetoprotein as our target since it is related to the development of liver cancer. There is no available antibody specifically recognizing this glycoform and therefore it is still challenging to utilize this parameter to evaluate the condition of patients. We chemoenzymatically synthesized alpha-fetoprotein-derived glycopeptides with core-fucosylation and subjected these immunogens to animal studies. The antisera displayed glycan-dependent IgG responses, laying a foundation to develop monoclonal antibodies that target the fucosylated alpha-fetoprotein. The discovery of such antibodies will be valuable to sensitively diagnose liver cancer in clinics. Lastly, developing enzyme tools is equally important to harness the field. In the final project of my dissertation, we revisited the substrate preference of the human α(1-6) fucosyltransferase. The enzyme exhibited a relaxed substrate preference when a proper glycoprotein, glycopeptide, or an Fmoc modification is attached to the acceptor substrates. This discovery provides new insights into studying glycosyltransferases and offers new approaches to chemoenzymatically synthesizing core-fucosylated glycoproteins and glycopeptides. Together, the studies present new avenues for studying glycan-related biological processes and diseases.
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    DISPARITIES IN PRE-EXPOSURE PROPHYLAXIS AWARENESS AMONG WOMEN: A SYSTEMATIC REVIEW OF THE LITERATURE AND LATENT CLASS ANALYSIS OF SYNDEMIC RISK FACTORS
    (2020) Stubbs, Leandra Nicole; Curbow, Barbara; Public and Community Health; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    While rates of HIV infection have declined among women in recent years, women still account for 19% of all new infections each year in the United States (US). Sociodemographic disparities remain with much of the burden falling on Black adult women aged 25-44. Ongoing transmission of HIV in this population has mostly resulted from heterosexual contact and prior studies have identified interpersonal and sociocultural factors that impede a woman’s choice to engage in safe sex and prevent HIV acquisition. With the debut of pre-exposure prophylaxis (PrEP), an FDA-approved once-daily pill to prevent HIV transmission, researchers believed that this user-controlled method would be an innovative method in reducing HIV in this subpopulation. However, since its release in 2012, there has been insufficient knowledge of PrEP among women in the U.S, resulting in slow and disproportionate uptake of PrEP in this population. While we know the clinical efficacy of PrEP, more understanding of the behavioral, social, and structural factors that impede PrEP awareness among women is important in the dissemination of PrEP-related information and subsequent use.In this dissertation, I took an exploratory approach to: a) identify awareness, knowledge, barriers and facilitators of PrEP use among US-based women through a systematic review; b) identify factors associated with PrEP awareness among female participants in the 2018 Community Health Survey; and c) explore how the presence of multiple deleterious factors can create distinct subgroups of women and further exacerbate disparities in PrEP awareness. In Paper 1, the systematic review of PrEP knowledge among Black/African American women identified 12 articles with findings disaggregated by both race and gender. Primary findings included gaps in PrEP knowledge; acceptability and willingness to use once informed of PrEP; perceived disadvantages as a result of exclusion in clinical trials and early dissemination; and social, structural, and institutional barriers to engagement in the PrEP care continuum. Papers 2 and 3 leveraged data from the 2018 Community Health Survey, a cross-sectional telephone survey of randomly selected adults aged 18 and older from all five boroughs of New York City. In Paper 2, 36% of a female subsample (N=2,295) were aware of PrEP at time of survey. As a result of multinomial linear regression, nine variables were significantly associated with PrEP awareness: nativity, education level, recent HIV test, number of sex partners, IPV, age, race/ethnicity, general health, and prior incarceration. In Paper 3, latent class analysis was used to identify distinct classes of women with varied responses to behavioral and structural variables. The adjusted item-response probabilities resulted in three distinct profiles of women: high resource and low risk group (39%), low resource and moderate risk group (33%), and moderate resource and high-risk group (28%). Key differences between groups include PrEP awareness, perceived health, count of sexual partners, and neighborhood poverty level. These findings have key implications for the way in which PrEP is marketed to women. Future studies should consider the importance of intersectionality and the social and structural context through which women engage with HIV prevention materials and promotional campaigns.
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    LEVERAGING SOCIAL NETWORKS TO FIGHT HIV: THE BATTLE OF FEMALE SEX WORKERS
    (2020) Li, Yuruo; Liu, Hongjie; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    This dissertation aims to assess the applicability of the social network method on HIV research among female sex workers (FSWs). Manuscript 1 reported the findings from a systematic literature review which examined the application of social network method in HIV studies focusing on FSWs. The majority of the identified studies were limited to local social networks or FSW establishments and did not use sophisticated statistical approaches to analyze sociocentric network data. The discrepancies in network definitions and data collections made it difficult in interpreting their findings and assessing validity. Most of the analytic plans for egocentric studies were limited to information at the individual level rather than that at the ego-alter ties. The project reported in manuscripts 2 and 3 used empirical data from a multi-center egocentric network study among mid-age FSWs in China to assess the extent to which social network components influence HIV testing behaviors (paper 2), and the associations between Chinese collectivist culture and FSWs’ social networks (paper 3). As reported in the manuscript 2, among 1,245 FSWs, 62.2% of them received an HIV test. HIV testing was positively associated with higher network transitivity (AOR: 1.77; 95% CI: 1.18-2.64) and inversely associated with network trust (AOR: 0.74; 95% CI: 0.56-0.97). Although social support was not associated with HIV testing, the increase in social cohesion may provide substantial support for HIV testing. As documented in manuscript 3, Chinese collectivism tendency was negatively associated with their perceived social support (95% CI: -0.33, -0.04), network effective size (95% CI: -0.30, -0.01), and network betweenness (95% CI: -0.33, -0.09). FSWs who had the highest level of collectivistic tendency and perceived a higher level of stigma are more likely to stay at a “bridging” position and connect with weak social ties rather than a strong cohesive group. This dissertation projects provide empirical evidence that social networks can be used to analyze the social environment of FSWs and its impact on HIV preventive behaviors among this HIV vulnerable population. The findings make additional contributions to the application of social network methods in social and behavioral research with a focus on FSWs.
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    HIGH-RESOLUTION ANALYSIS OF HIV ENVELOPE-SPECIFIC ANTIBODY RESPONSES TO ACCELERATE RATIONAL IMMUNOGEN DESIGN
    (2020) Lei, Lin; Li, Yuxing; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The recent isolation of HIV broadly neutralizing antibodies (bNAbs) from HIV infected individuals has reinvigorated efforts to develop B cell-based vaccines. As the sole viral target for bNAbs, HIV envelope glycoprotein (Env) has been engineered as soluble trimers to recapitulate bNAbs responses via vaccination. However, Env-based immunogens thus far primarily induce vaccine-matched neutralizing antibody (nAb) responses. This thesis aims to understand the mechanisms restricting the neutralization breadth and to provide strategies for iterative improvements. First, we have established an antigen-specific single B cell sorting and monoclonal antibody (mAb) cloning platform for guinea pigs, a small animal model desirable in the field for initial immunogenicity analysis. This method allowed us to dissect the antibody responses at the clonal level with high accuracy and efficiency. Secondly, we have delineated the specificity of autologous neutralization elicited by the current generation HIV trimer mimicry, BG505 SOSIP.664. Our results reveal a prominent epitope in the C3/V4 region of the Env targeted by one nAb/B cell clonal lineage. We demonstrate that the nAb responses to this neutralization determinant are prevalent in trimer-vaccinated guinea pigs, rabbits, and non-human primates. In addition, this defined nAb response shares a high degree of similarity with the early nAb response in an HIV- infected pediatric patient, who later developed a bNAb response. This study offers insights into re-designing Env immunogens in the highly immunogenic region to broaden nAb responses. Lastly, we have engineered novel immunogens based on the Env sequence of a virus strain isolated from bNAb VRC01 donor, which can engage the VRC01 germline precursor in vitro. Sequential prime-boost immunizations in a VRC01-germline immunoglobulin (Ig) encoding genes knock-in mouse model with the designed immunogens induced focused VRC01-like serum antibody responses and clustered VRC01-class somatic mutations in the knock-in VRC01-germline Ig genes. In addition, the mAbs recovered from the immunized mice neutralize selected viruses containing the N276 glycan, a critical roadblock impeding the affinity maturation of VRC01-class bNAbs. Our findings demonstrate that, in the transgenic mouse model, our immunogens effectively activate bNAb precursor B cells and guide their affinity maturations required for bNAb function, which has important implications for HIV vaccine development.
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    WHAT IS BEAUTIFUL IS SAFE: PHYSICAL ATTRACTIVENSS AND PERCEPTIONS OF STI RISK AMONG MEN WHO HAVE SEX WITH MEN
    (2018) Sarno, Elissa Louise; Mohr, Jonathan J; Psychology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Men who have sex with men (MSM) are the group most severely impacted by HIV in the United States (CDC, 2015). Many MSM, however, still engage in sex without condoms (Smith, Herbst, Zhang, & Rose, 2015). One factor influencing a lack of condom use among MSM may be an assumption of low risk of contracting HIV or another STI from physically attractive partners. This assumption may be particularly dangerous for MSM who use geosocial networking applications (GSN) to find sexual partners. Previous researchers have suggested that this assumption could be based on two theoretical mechanisms: implicit personality theory and motivated reasoning. The present study tested two hypothesized models of the associations between physical attractiveness, perceived HIV/STI risk, and condom use intentions, based on these proposed theories. Participants were 197 MSM who completed an online survey in which they viewed photos of physically attractive and unattractive men and responded to items on perception of positive partner personality characteristics, intention to have sex with the partner, perceived risk for HIV/STIs, and condom use intentions. Results supported both theories. Specifically, physical attractiveness was negatively associated with perceived risk for HIV/STIs and condom use intentions, and these relations were mediated by intentions to have sex and positive partner personality. Implications of these findings for further research and practice are discussed.