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The widespread availability of antiretroviral therapy (ART) for HIV infection in Sub-Saharan Africa (SSA) has resulted in decreased morbidity, mortality, and transmission of HIV. This region, however, still represents the majority of the global burden of HIV. Furthermore, levels of retention in care and medication adherence, critical determinants of ART effectiveness, are currently suboptimal, and, thus, continue to be the target of many interventions. This dissertation is comprised of three chapters related to understanding ART adherence and interventions to improve it.Chapter 1 quantitatively describes and examines the distribution of poor adherence to antiretroviral therapy in a study of HIV-positive patients in Zambia. In a novel application of the Lorenz curve, a tool used commonly in economics, this analysis characterized the concentration of medication non-possession in a network of clinics in order to identify “hotspots” and predictors of poor adherence. Results extend previous studies by revealing that even though average adherence is high, lapses in adherence are common and concentrated among a minority of patients, and also in certain clinics. This concentration and variability varies with time on ART. Furthermore, a small fraction of patients accounts for the majority of days of medication non-possession, with the size of this group increasing with time on ART. This suggests that targeted interventions may represent a preferable overall strategy as compared to those targeting all patients to improve adherence. Furthermore, there was high variability across clinics suggesting that interventions targeting clinic “hotspots” may also represent an efficient use of resources to improve ART adherence. Chapter 2 presents the results of the first qualitative study to examine conditional incentives for ART adherence and their potential pathways of action among people living with HIV. This study was conducted within a study of conditional food and cash transfers to increase retention in care and adherence to ART among HIV-positive food insecure recent adults in Shinyanga, Tanzania. Although financial and in-kind incentives have been shown to improve outcomes along the HIV care cascade, results are mixed, and there is little evidence about the pathways through which incentives work. Results of this qualitative study and analysis revealed that incentives acted through three primary pathways to potentially increase retention in care and adherence to ART: 1) addressing competing needs and offsetting opportunity costs associated with clinic attendance, 2) increasing motivation and 3) alleviating stress associated with attending clinic, worry about providing for oneself and one’s family, and providing hope for a better future. The first pathway was the strongest, which was consistent with field observations and discussions with local clinic staff, research staff, and Ministry of Health officials. Participants did not report any harmful events associated with the incentives, and reported a variety of beneficial spillover effects on household welfare. Understanding these pathways can help improve design and targeting of future food or cash incentive interventions. Chapter 3 focused on intrinsic motivation within the aforementioned study of food and cash transfers for ART adherence in Tanzania. Some critical of incentives argue that incentives can ‘crowd out’ intrinsic motivation, making the individual less likely to engage in the desired behavior after the incentive is removed, potentially leading to limited durability of effect and causing harm in the long term. This hypothesis was examined among recent antiretroviral treatment initiates in Tanzania by comparing participants’ level of intrinsic motivation before receiving transfers to the level once the transfer period ended. The analysis revealed that, not only did intrinsic motivation not decrease after the transfer period ended, but that the level of intrinsic motivation increased overall and within study arms. Furthermore, the change in motivation did not differ by study arms. As the first study to empirically examine the crowding out hypothesis regarding incentives in a real-world, resource-limited setting, these results suggest that incentive interventions in such settings should not be impeded by concerns of crowding out intrinsic motivation.Together these chapters contribute to improving our understanding of antiretroviral adherence and intervention response. The Lorenz curve and medication possession analysis provides a more comprehensive and detailed measurement and illustration of adherence and its variability across individuals and clinics in Zambia. Such information is critical to targeting and designing future interventions. Next, by examining an ongoing intervention to improve adherence in Tanzania, we were able to elucidate and examine the potential pathways of action of food and cash transfers. Furthermore, we found no evidence that these incentives decreased intrinsic motivation. Knowledge gleaned from this deep exploration of the incentives’ mechanism of action in a real-world setting not only informs refinement of the intervention, but also helps to fill the gap in understanding how and when these interventions may work.

The introduction of Antiretroviral Therapy (ART) in the late 1980s has transformed HIV from a fatal disease into a manageable chronic condition, although challenges like adherence to treatment and broader socio-economic factors continue to impact viral suppression and overall health status among people living with HIV (PLWH). The objective of this dissertation is to examine social (community environments), biological (pain), and psychological (self-perceived quality of life) factors associated with viral suppression among PLWH.The first paper investigates the association between neighborhood and sociodemographic factors and viral suppression among PLWH in Southern California, focusing on areas served by Ryan White clinics. Contrary to expectations, higher walkability scores were associated with lower levels of viral suppression. In line with our hypotheses, longer commute times were negatively associated with viral suppression. Employment showed a positive association with viral suppression, while higher poverty levels and longer work hours negatively impacted viral suppression rates. Additionally, no significant relationships were found between education level, public transportation score, and viral suppression. Given that PLWH often report higher instances of pain and substance use compared to the general population, the second paper explores the association between pain and viral suppression and how substance use modifies this relationship. We found that there was no substantial association between pain and viral suppression among women living with HIV (WLWH) in our cohort. Furthermore, we saw no modification by any type of substance use. The third paper examines the role of quality of life (QoL) on viral suppression and any disparities in this association by race/ethnicity. QoL encompassing physical health, psychological well-being, and socioeconomic stability, has been consistently linked to viral suppression. We found a significant positive association between QoL and viral suppression (aOR: 1.17, 95% CI [1.10, 1.25]). However, the magnitude of this association was shown to vary by racial and ethnic group. The increase in odds of viral suppression per one-point rise in QoL score was greatest among White WLWH and least among Black WLWH. Understanding the individual impact of each factor examined allows for the development of targeted, effective interventions. These findings not only advance our knowledge of HIV management but also emphasize the need for a multi-faceted approach that addresses the specific needs and circumstances of individuals living with HIV.

Background: Women who inject drugs face vast disparities in health outcomes relative to their counterparts in the general population, most notably in HIV. Intimate partner violence (IPV) victimisation has a detrimental individual effect on women's HIV risk behaviour. Furthermore, IPV often co-occurs with substance use and poor mental health among women in high-income countries, but little is known about the cumulative and interactive effects of these conditions on women's HIV risk behaviour in low- and middle-income countries. This thesis applied an ecological approach guided primarily by syndemics theory to understand influences on women's HIV behavioural outcomes. It examined associations and mechanisms linking IPV, substance use, and depression, with HIV sexual and injecting risk outcomes in the first quantitative study of Indonesian women who inject drugs, the Women Speak Out study. Methods: This study combined community-based participatory approaches and extensive formative research with quantitative survey methods. 731 women, ≥18 years of age, and injecting illicit drugs in the preceding year were recruited using respondent-driven sampling (RDS) from urban settings in Greater Jakarta and Bandung, Indonesia. Network characteristics of the sample were assessed using the RDS software package for Stata 14. Data were analysed using multivariate logistic regressions, marginal effects models, and interaction analyses on the additive and multiplicative scales. The study was conducted in collaboration with the Indonesian Drug User Network. Results: Paper 1: Past-year IPV victimisation doubled the odds of engaging in one or more sexual HIV risk behaviours. Several covariates were associated with higher odds of sexual risk behaviour: HIV-positive status, non-injection crystal methamphetamine (crystal meth) use, low educational attainment, younger age, and being single. Co-occurrence of psychological, physical and/or injurious, and sexual forms of IPV had cumulative effects: sexual risk behaviour was reported by 62% of women who did not experience any form of IPV, but increased to 89% among those exposed to all three forms. Paper 2: Past-year IPV elevated women's odds of receptive syringe sharing. These effects remained after controlling for socio-demographic confounders. Two covariates, injecting illicit pharmaceuticals (vs heroin only) and housing instability and/or homelessness, remained associated with receptive syringe sharing in multivariate analyses. Paper 3: More than 1 in 4 women experienced concurrent IPV, depressive symptoms, and crystal meth use. All three exposures had independent negative effects on HIV sexual risk outcomes. The co-occurrence of all three factors produced a 4-fold increase in rates of survival sex work, 5-fold increase in STI symptomatology, and a 7-fold increase in inconsistent condom use. The joint effect of depressive symptoms and crystal meth use together was greater than the product of the estimated effects of each exposure alone on STI symptomatology, indicating an interaction on the multiplicative scale. Statistically-significant positive additive interaction was detected between IPV victimisation and crystal meth on inconsistent condom use; depression and crystal meth on STI symptomatology and on survival sex work; and IPV and depression on STI symptomatology and survival sex work. Conclusion: This thesis provides new evidence of the individual and cumulative effects of IPV, methamphetamine use, and depression on HIV risk outcomes among Indonesian women who inject drugs. The interaction analyses are the first to empirically test the assertion that these co-occurring conditions interact synergistically to increase drug-using women's HIV risk. This thesis furthers our understanding of how syndemics function within women who inject drugs to produce health disparities, and contributes to the problem theory for HIV risk behaviour in this population. The findings of this study have great public health significance and important implications for future longitudinal research, interventions, and policy.

Background: Sub-Saharan Africa is home to 85% of the world's HIV-positive adolescents: an estimated 1.3-2.2 million 10-19 year olds. Adolescents living with HIV face multiple sexual and reproductive health risks: unwanted pregnancies and the risk of mother-to-child-transmission, risk of infecting partners, co-infection with other STIs, and the rising but undocumented risk of re-infection by potentially resistant HI-virus strains. Using contraception, especially condoms, is particularly challenging for all adolescents. It is even more difficult for HIV-positive adolescents due to HIV-related factors such as learning their HIV-positive status, withholding or disclosing their HIV-status to sexual partners, and accessing services in the home, clinics, and schools. This thesis aims to understand which factors shape sexual risk-taking among HIV-positive adolescents to inform the development of interventions that promote safe sexual practices in this population. Methodology: This thesis applies a socio-ecological model to investigate factors associated with sexual risk-taking among HIV-positive adolescents. It consists of three stand-alone papers: a systematic review and two quantitative papers based on a cross-sectional epidemiological and aetiological study of unprotected sex among HIV-positive adolescents and community controls in South Africa. Paper 1 is a systematic review of rates, correlates, and interventions to reduce sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa. Paper 2 looks at associations between HIV-status knowledge and disclosure and protective sexual practices in the cross-sectional study sample. Paper 3 explores the relationship between various social protection provisions and unprotected sex among HIV-positive adolescents. The candidate co-developed and conducted a community-traced study of adolescents in the Eastern Cape, in South Africa: 1,060 HIV-positive adolescents and 467 community controls. HIV-positive 10-19 year old adolescents were recruited from 53 government facilities in a health sub-district with antenatal HIV prevalence of over 30%. 90.1% of the eligible sample was traced, with only 4.1% refusing to take part. Community controls were neighbouring or co-habiting 10-19 year old adolescents, 92% of whom agreed to take part. Voluntary informed consent was obtained from adolescents and caregivers in the language of their choice: English or Xhosa. Questionnaires were administered by trained research assistants using mobile devices (tablets) with adolescent-friendly graphic content to ensure participant interest and reduce participant burden through skip-patterns. The systematic review (Paper 1) included studies located through electronic databases and grey literature. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Quantitative studies reporting on HIV-positive participants (10-24 year old) included data on at least one of eight outcomes (early sexual debut, inconsistent condom use, older sexual partner, transactional sex, multiple sexual partners, sex while intoxicated, sexually transmitted infections, and pregnancy). Only studies conducted in sub-Saharan Africa were included. The candidate and a second author independently piloted all processes, screened studies, extracted data independently, and resolved any discrepancies. Due to variance in reported rates and correlates, no meta-analyses was conducted. The systematic review informed the analyses conducted for the two quantitative papers. Analyses for Papers 2 and 3 used condom use at last sexual encounter (dichotomised either as safe sex/abstinence or unprotected sex) as the outcome, controlling for a series of covariates. Analyses used SPSS 22 and STATA 11. For each paper, the hypothesised factors were entered as independent variables in multivariate logistic regressions controlling for potential confounders. Based on the findings of the systematic review, gender moderation analyses was run entering a 2-way interaction term of gender*correlate in multivariate logistic regressions, controlling for covariates. Marginal effect models explored the effect of combinations of risk/ protective factors. Predicted probabilities for safe sex/ unprotected sex were computed for different two- and three-way combinations of the independent variables, controlling for covariates significantly associated with the outcome. Paper 2 tested the effect of three types of disclosure on protective sexual practices: (i) knowledge of one's own HIV-positive status, (ii) disclosing one's HIV-status to a partner, and (iii) knowing a partner's HIV-status. It compared HIV-positive status aware adolescents (n=794) with the rest of the sample (n=733). Paper 3 investigated associations between nine types of social protection provisions and unprotected sex. In line with UNICEF's definition, social protection was defined as any provision aimed at preventing, reducing and eliminating economic and social vulnerabilities to poverty and deprivation among HIV-positive adolescents. The nine social protection provisions tested by the analyses included ‘cash' and ‘care' factors accessed in the home, school, and community. Results: Paper 1 – ‘Sexual Risk-Taking among HIV-Positive Adolescents and Youth in Sub-Saharan Africa: A systematic review of prevalence rates, risk factors, and interventions.' The systematic review (Chapter 4) found that, despite their heightened vulnerabilities and high rates of sexual risk-taking, there is a dearth of evidence on interventions which may help HIV-positive adolescents engage in safe sexual practices. The review included 35 studies, four of which were interventions aiming to reduce sexual risk-taking. The quality of the included studies was low with most studies (k=31) reporting findings from cross-sectional data. HIV-positive adolescents and youth reported high rates of sexual risk-taking, however findings were inconsistent about potential factors associated with sexual risk-taking. Factors consistently associated with sexual risk-taking in multivariate analyses included: food insecurity, living alone, living with a partner, and gender-based violence. No significant associations were reported for: rural residence, informal housing, anxiety, religious guidance, STI prevention knowledge, poor birth outcomes, orphanhood, parental monitoring, having a supportive family, social support, maternal education level, poverty, disclosing one's HIV-status to a partner, time on ART, ART adherence, receiving care at a hospital, opportunistic infections. However, most of the above associations were reported by only one study, therefore further analyses is needed to build the evidence base on potential determinants of sexual risk-taking among HIV-positive adolescents and youth. The included interventions consist of three individual- and group-based psychosocial interventions evaluated in three small-scale trials (n<150) and one large trial of combination interventions for HIV-positive orphaned adolescent girls (n=710). Three of these interventions had positive effects in reducing sexual risk-taking: an individual based 18-session counselling intervention in Uganda, a support group intervention in South Africa, and a combination intervention in Zimbabwe. Quantitative data analyses of cross-sectional study data: Overall, adolescents in the full sample (n=1,527) reported high rates of sexual activity (34.9%) and high rates of unprotected sex (22%), with adolescent girls reporting higher rates of unprotected sex than boys (33% vs. 7%).

Low- and middle-income countries are increasingly under pressure to determine how to integrate their donor-driven health programs into locally-run health programs. Voluntary Medical Male Circumcision (VMMC) is a cost-effective, evidence-based HIV prevention strategy. It has been shown to reduce female to male transmission of HIV by 60%. The World Health Organization and UNAIDS recommend VMMC in 15 countries. These East and Southern African countries have high HIV prevalence rates, where heterosexual sex is the main driver of HIV transmission, and there are low circumcision prevalence rates in some or all populations. External donors such as the United States President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, TB, and Malaria (GFATM) are seeking to withdraw financial support for the VMMC program, despite its potential contribution to ending the HIV/AIDS epidemic, because they feel that national governments should be able to continue the program at steady-state. According to PEPFAR, mathematical modeling shows that reaching high levels of VMMC coverage can “…dramatically reduce community-level HIV incidence and save billions of dollars in HIV care and treatment costs. The imminent withdrawal of donor funding has stimulated national governments to mobilize domestic resources and take responsibility for the oversight and operations of the program from NGOs. In Zimbabwe, there is political will from the government to take on the VMMC program, as evidenced by the national VMMC Sustainability Transition Implementation Plan. According to this plan, the sustainability of the VMMC program calls for an integrated, decentralized, and locally owned program. The vertical (or stand-alone) program will be integrated into existing health services. The availability of the procedure at primary health centers will depend on training of more service providers. Decentralization will require a transfer of management responsibilities from implementing partners to subnational government stakeholders, a consolidation of roles, and greater community engagement. In the first paper, Managing change to integrate and sustain a vertical, donor-funded program: a case study on Voluntary Medical Male Circumcision in Zimbabwe, I develop a business-school-style teaching case study that uses an example of a health program that is undergoing a transition from a vertical program to a horizontal health program. The VMMC program in Zimbabwe must make changes to its operating model to sustain the program in preparation for the eventual withdrawal of donor funding. It must also transition from a program that is donor and implementing partner led to one that is government owned and operated. This case study illustrates how a health program pivots after a period of disruption (in this case the COVID-19 pandemic); the likelihood of successful change when leadership is shared rather than dependent upon one individual; and how a team can participate in a process to prioritize addressing a problem and mobilize collective action to resolve it. In the second paper, Sustainable integration of a vertical Voluntary Medical Male Circumcision program into routine health services in Zimbabwe: a mixed methods process evaluation of a participatory change intervention, I address whether a systems change intervention called the LEAD Framework furthered the integration and sustainability of the VMMC program. I focus on how the intervention facilitated the transition of VMMC within five pilot districts into a locally-owned and managed program while also strengthening individual and team capacity. District team actions included greater engagement of multisectoral stakeholders, better use of existing resources, and changes to operating models. I observed improvements across all World Health Organization health system building blocks, suggesting that the intervention strengthened the overall health system. A sustainability survey showed a reduction in funding stability but a significant increase in communications, program adaptation, and organizational capacity. In the third paper, Understanding stakeholder perspectives on integrating and sustaining voluntary medical male circumcision into routine health services in Zimbabwe: a qualitative study, I describe the range of psychological and structural barriers and facilitators faced by a broad array of stakeholders engaged in integrating and sustaining the VMMC program. Notably, staffing and financing barriers, particularly the obstacles posed by staff attrition, limited domestic resources, and the transition from a fee-for-service to a facility-based performance model, will make decentralized service delivery and maintaining high levels of productivity challenging. Respondents also mentioned resistance to changing the program's operations as a significant barrier, especially as donors and partners continued to control the funding, thereby limiting the Ministry of Health and Child Care's (MoHCC) decision-making power. However, stakeholders saw an opportunity for increased responsibility and a greater sense of ownership at the subnational level through the decentralization of governance. As a whole, this dissertation provides a description of how a transition of the VMMC program in Zimbabwe from a vertical program to a horizontal program can be facilitated through a participatory, bottom-up systems change intervention called the LEAD Framework, answering research questions not previously addressed in the literature and suggesting next steps for countries undergoing similar processes.

Background: Since the onset of the HIV epidemic, antiretroviral therapy (ART) has lengthened the lives of people living with HIV (PLWH). More than half of the population of PLWH are 50 years and older, and as the aging population of PLWH expands it is important to consider the environmental, socio-structural, and biological factors and pathways that impact aging with HIV (Centers for Disease Control and Prevention [CDC], 2018). It is estimated that about a third to one half of HIV-seropositive individuals have some degree of cognitive impairment (Heaton et al., 2010), though prevalence may be lower in populations with sustained viral suppression (V. Valcour, personal communication, December 2018). Studies show that various measures of loneliness and social isolation are associated with risk for cognitive impairment and dementias among the general population (Kuiper et al., 2015, 2019). Literature also indicates that, on average, PLWH experience more loneliness and social isolation than HIV-seronegative individuals (Greene et al., 2018; Grov et al., 2010; Poindexter & Shippy, 2008). In addition to the environmental and social factors that impact risk for cognitive impairment among PLWH, the study of inflammatory processes and biomarkers—and whether these are important for the development of HAND—is an important area of current research (Office of AIDS Research [OAR] Working Group on HIV and Aging, 2012). Current evidence demonstrates an overall increased risk of morbidity and mortality in HIV-positive individuals whose CD4/CD8 ratio fails to normalize above 1.0 (Mussini et al., 2015; Serrano-Villar et al., 2013, 2014). Additionally, a small number of studies show that inverted CD4/CD8 ratio is associated with the development of neurocognitive disorders (Correa et al., 2014; Grauer et al., 2015; Rawson et al., 2015; Vassallo et al., 2017). Problem Statement: The central hypotheses motivating this dissertation research is that loneliness and social isolation represent two distinct and uniquely important factors in the risk of cognitive impairment among people aging with HIV, and that CD4/CD8 ratio is an endophenotype that may help elucidate the pathways by which physical health, mental health, and environmental factors impact cognitive impairment among PLWH. Chapter 2: The 2nd chapter of this dissertation systematically examined the current body of quantitative literature about social support and loneliness and cognitive impairment among PLWH. We used meta-analysis to summarize the association of these variables and used meta-regression to identify moderating variables in N=11 studies. Among the 11 studies reviewed, many were limited by the use of un-validated measures of loneliness and/or social support as well as heterogeneous measures of cognitive symptoms and cognitive performance. The meta-analysis (n=10) showed a positive association between social isolation or loneliness and cognitive impairment. Though there was moderate heterogeneity among the studies analyzed, there was not substantial publication bias. Meta-regression showed moderation of the association by study quality, older age (≥55 years), and study country but not by sample mean CD4 cell count. This paper highlights knowledge gaps in the current body of research and reflects distinctions between performance-based and self-reported measures of cognitive impairment as well as various dimensions of social connectedness. Chapter 3: Building on the knowledge gaps identified in the second dissertation chapter, the 3rd chapter of this dissertation examined the association of both loneliness and social isolation with performance based cognitive impairment and subjective cognitive complaints in a sample of older adults living with HIV and confirmed HIV-Associated Neurocognitive Disorders (HAND). We performed a cross-sectional, secondary data analysis in a cohort of older adults living with HIV recruited at the Memory and Aging Center (N=171). This paper revealed that loneliness was correlated with mental health variables (depression, anxiety, and perceived stress) while social isolation was correlated with other marginalized conditions and socioeconomic factors (lower years of education, history of Hepatitis C (HCV), history of a substance use disorder, and Black/African American race, and area-level socioeconomic environment). This paper also showed that social isolation, but not loneliness, was associated with higher odds of impairment in two cognitive domains (Attention and Executive function [ATT] and Speed of Processing [SPD]). We concluded that social isolation may be conceptualized as a pathway of embodiment, reflecting experiences of marginality that could impact risk of HAND. Chapter 4: The 4th chapter of the dissertation used an exploratory, cross-sectional secondary analysis of the the Hawaii Aging with HIV Cardiovascular Study (HAHCS) cohort-Public Data Set. We aimed to examine the relationships between CD4/CD8 and biomarkers of inflammation among middle-aged and older adults living with HIV (N=103). This study revealed that the lowest tertile of CD4/CD8 ratio (Median: 0.346, range 0.123-0.501) was associated with a higher inflammation profile and higher concentration of mature monocytes in the blood. In elucidating the CD4/CD8 cell ratio among PLWH, this paper contributes to the body of evidence that suggests a link between CD4/CD8 ratio and established risk factors for HAND among middle-aged and older adults with HIV. Chapter 5: The 5th chapter of the dissertation was a longitudinal study of the Women’s Interagency Health Study (WIHS) public data set to examine the intra-individual variability of the CD4/CD8 ratio over 10 years as well as clinical and sociodemographic correlates of CD4/CD8 ratio among women living with HIV (n=1462). This study revealed that, over 10 years, the CD4/CD8 ratio remained relatively stable. Over time, decreased CD4/CD8 ratio was associated with higher age, detectable viral load, and sub-optimal ART adherence. We then examined associations of clinical and sociodemographic with “inverted” CD4/CD8 ratio (≤ 1.0 versus >1.0) and “low” CD4/CD8 ratio (≤ 0.70 versus >0.70). This paper revealed that inverted and low CD4/CD8 ratio were both associated with detectable viral load and fewer years of educational attainment. Because much of the WIHS sample had a CD4/CD8 ratio that was below 0.50, in addition to the findings from chapter 4 that indicate inflammation is association with the lowest tertile of CD4/CD8 ratio (0.123-0.501), we subsequently performed a follow-up analysis to examine variables associated with “very low” CD4/CD8 ratio (≤0.50 versus >0.50). We found that very low CD4/CD8 ratio was associated with older age, detectable viral load, past/current Hepatitis C, white racial group, and lower educational attainment. Overall, the findings from this paper show that CD4/CD8 ratio was relatively stable over time, but was significantly influenced by age, viral load, and adherence to ART medications. We also found that inverted, low, and very CD4/CD8 ratio were all associated with fewer years of education. In linking CD4/CD8 ratio to lower educational attainment, our study implicates immune function as a pathway by which root causes and social determinants of health (SDOH) may impact risk of cognitive impairment among women with HIV.

The government regularly outs information concerning people's sexuality, gender identity, and HIV status. Notwithstanding the implications of such outings, the Supreme Court has yet to resolve whether the Constitution contains a right to informational privacy - a right to limit the government's ability to collect and disseminate personal information. This Article probes informational privacy theory and jurisprudence to better understand the judiciary's reluctance to fully embrace a constitutional right to informational privacy. The Article argues that while existing scholarly theories of informational privacy encourage us to broadly imagine the right and its possibilities, often focusing on informational privacy's ability to promote individual dignity and autonomy, there is a disconnect when courts attempt to translate those theories into workable doctrine. The extant theories are products of Fourth Amendment and decisional privacy law, and bear a more attenuated relationship to informational privacy problems, hindering recognition of the right. This Article reorients and hones the focus of the purported informational privacy right toward what the Due Process Clause suggests as the right's two principal and more concrete values: preventing intimate information from serving as the basis for potential discrimination and creating space for the formation of political thought. By so doing, not only is a more precise theory of informational privacy constructed, but instrumentally (and perhaps most importantly), courts will be more apt to recognize a constitutional informational privacy right thereby better insulating individuals from discrimination or marginalization.

Preventing the spread of blood-borne infectious diseases is vital to improving global health outcomes, particularly for low- and middle-income countries (LMICs). Sensitive and accurate diagnosis of infections is vital to this effort. Nucleic acid amplification tests (NAATs), which amplify pathogen nucleic acids, are gold-standard techniques for detection and quantification of pathogen levels. However, standard NAATs such as polymerase chain reaction (PCR) require expensive equipment for blood sample processing and DNA/RNA amplification, making them challenging to implement in resource-limited areas of LMICs. In this work, I developed two methods to simplify sample processing and amplification to make NAATs more accessible for use at the point of care in resource-limited areas of LMICs. The first method enables instrument-free nucleic acid extraction from whole blood. A room temperature lysis chemistry and a paper-and-plastic sample capture device were developed to isolate, purify, and store pathogen DNA and RNA on a paper capture membrane. Extracted nucleic acids can be eluted and used in standard NAATs or in developmental amplification assays. I demonstrated successful isolation of HIV virion RNA and P. falciparum parasite DNA from whole blood samples over several concentrations with >60% recovery. Extracted RNA remains stable on the capture membrane for two weeks at room temperature and 37°C, alleviating the need for cold storage after sample collection. These results are a promising step toward using this method for simplified sample extraction and storage in low-resource settings in LMICs. The second method I developed is a novel isothermal amplification technique for P. falciparum DNA. Sensitive diagnosis of P. falciparum infection is vital to identify and treat low-density, asymptomatic infections and move closer to eliminating malaria. Highly sensitive PCR assays are difficult to deploy in resource-limited areas of LMICs and existing isothermal methods require complex assay design and are often not sensitive enough to diagnose asymptomatic infections. Here, I developed a novel isothermal technique which amplifies multiple regions of the P. falciparum genome, generating a large amount of DNA for better analytical sensitivity. The assay achieves a lower limit of detection of ~23.4 fg P. falciparum gDNA/µL (~1 parasite/µL) in 30 minutes, similar gold-standard PCR assay while using a fraction of the resources required for PCR. Lastly, I adapted the assay for implementation at the point of care. I showed that the assay directly amplifies P. falciparum parasite DNA captured on paper with the paper-and-plastic device previously developed. I also incorporated visual assay readout with lateral flow strips, eliminating the need for specialized equipment to detect amplified DNA. I explored methods to eliminate cold storage of reagents by stabilizing amplification enzymes at room temperature. The work described in this thesis represents two enhanced methods for point of care detection of blood borne pathogens. By simplifying sample extraction, amplification, and detection, the methods described here make NAATs more accessible to low-resource areas of LMICs. The whole blood nucleic acid extraction device and isothermal assay described in this work can be used together for sensitive diagnosis of P. falciparum malaria. The methods can also be used independently, or in combination with other techniques routinely used in the field. The flexibility built in to these methods enables easier integration into existing workflows in LMICs.

Certain populations are disproportionately affected by HIV, irrespective of epidemic type. In Uganda, female sex workers (FSW) and men who have sex with men (MSM) are two highly stigmatised, criminalised populations. As Ugandan FSW and MSM populations have been understudied in the context of the generalised epidemic, and current HIV responses are directed towards the general Ugandan population, it is difficult to assess the magnitude of HIV in these key populations. To address this gap, two qualitative studies and one quantitative study were conducted in 2019. The first study involved in-depth interviews with 16 MSM that explored contexts of HIV risks and experiences of accessing HIV testing, care, and treatment in a rural setting in Uganda. The second study was a quantitative analysis of 524 FSW on PrEP that used structured paper-based interviews to explore real-world experiences of PrEP use, HIV risk and sexual behaviours. The third study was a qualitative sub-study of the second study. It comprised 20 in-depth interviews with FSW in a rural Ugandan setting. This study explored knowledge, perceptions, adherence and attitudes to PrEP use. Key findings illustrated high HIV risk among MSM with a diverse range of barriers and facilitators affecting access to HIV prevention services. Both FSW and MSM employed a range of strategies to reduce their HIV risk. Other important findings among FSW included high protective adherence levels to PrEP as measured by pill count and self report and that sex was reported to be more pleasurable with PrEP use, with concurrent reduced HIV-related worry. This thesis contributes to the knowledge of HIV risk and prevention strategies among criminalised and highly stigmatised key populations in generalised HIV epidemics. It draws on a socio-ecological framework to understand how these key populations navigate health care services, providing useful information on real-world PrEP use as an important biomedical prevention strategy. The conclusion supports a combination HIV prevention strategy to generate sustained reductions in HIV incidence among stigmatised populations in Uganda.

Antiretroviral therapy (ART) has played a key role in extending the longevity of individuals infected with HIV. Although life expectancy increased significantly, aging with the virus has presented a new study of interest as neurocognitive impairments begin manifestations in individuals living with HIV. These manifestations lead researchers to investigate the involvement of HIV and HIV-associated neurodegeneration (HAND). As interest in this area grows, researchers demonstrate the current pathology of neuro-HIV and the damage manifests in HAND patients. The current neuropathology of HIV neuronal damage demonstrates the initiation of CD4 and chemokine coreceptors, CCR5 and CXCR4 in the brain to activate macrophages and microglia for the release of neurotoxic substances to neurons. The use of ART has provided a decreased incidence of extreme neurological impairments in HIV patients, yet, there were no significant changes to the overall incidence of HAND with ART, producing a gap for treatment against neuro-HIV. Many researchers are currently investigating different targets in neuro-HIV pathogenesis, such as chemokines, cytokines, leukotrienes, etc., to inhibit inflammatory responses that could be used as potential treatments for neuroprotection. Montelukast is a cysteinyl-leukotriene receptor 1 antagonist, initially used as an anti-inflammatory drug for asthma. Cysteinyl leukotrienes have been shown to correlate with the inflammatory response of neuro-HIV, which is why we want to see if the drug will inhibit this response and demonstrate neuroprotection in HIV-infected brains. In this paper, we will investigate the effects of a cysteinyl leukotriene receptor 1 antagonist, Montelukast in HIV gp120 mice We will conduct a 2-month administration of Montelukast and saline to HIV-gp120 transgenic and wild-type mice and then analyze the effects of the Montelukast through immunofluorescence staining and statistical analysis. Our findings suggest the neuroprotective effects of Montelukast on MAP-2-positive neuronal dendrites, presynaptic synaptophysin-positive terminals, and Iba-1-positive microglia in the cortex. Iba-1 also demonstrated a significant decrease of microglia in the hippocampus, an indication of neuroprotection in the brain. However, no other significant changes indicating neuroprotection were observed in HIV-gp120 transgenic mice treated with Montelukast.

Adherence to medications for HIV prevention and treatment is essential to reducing HIV transmission risk and improving health outcomes. Adherence to these medications remain insufficient in several key populations, however. Understanding how partnership types and dynamics may encourage or hinder HIV medication adherence is necessary to improving adherence rates among important sub-groups, including young men who have sex with men (YMSM), serodiscordant couples, and adolescent girls.My first paper identified the partnership and housing factors associated with adherence to oral PrEP among YMSM. PrEP adherence was relatively low in the study, declining from 46% at baseline to 39% at study conclusion. PrEP adherence was significantly associated with increasing age (OR=1.35; 95% CI: 1.14, 1.60), and race (African-Americans vs. other OR=0.37, 95% CI: 0.21, 0.66). Relationship type, length, and depth, number of partners, and partner’s HIV status were not significantly associated with adherence. PrEP adherence was associated with housing insecurity, including ever being kicked out of the home (AOR=0.43; 95% CI: 0.18, 1.04), and the Housing Insecurity Index (AOR=0.64; 95% CI: 0.44, 0.93). PrEP adherence was also associated with privacy, including number of people living in the residence (AOR=0.82; 95% CI: 0.71, 0.95), sleeping in a private bedroom (AOR=2.10, 95% CI: 1.01, 4.40), and the Lack of Privacy Index (AOR=0.82; 95% CI: 0.71, 0.95). YMSM did not modify their PrEP-taking depending on relationship risk. Housing insecurity and lack of privacy may hinder PrEP adherence among YMSM.My second paper determined whether HIV viral suppression was associated with partnership status and partnership support among HIV-positive individuals and serodiscordant couples in Brazil. Viral suppression did not significantly differ between HIV-positive partnered (79% virally suppressed) and unpartnered (76% virally suppressed) individuals. Among individuals in partnerships, viral load suppression was significantly associated with having partners who attended monthly visits (AOR=2.99; 95% CI: 1.00, 8.93); among women in partnerships, viral load suppression was significantly associated with having a partner who actively reminded them to take ART (AOR=2.67; 95% CI: 1.04, 6.88). Practical measures of social support, including attending monthly visits and reminding a partner to take ART, may improve viral suppression among HIV-positive individuals in serodiscordant partnerships.My third paper assessed the product, relationship, and sex factors that affect acceptability of a vaginal ring (VR) for HIV prevention among adolescent girls aged 15 to 17 years. Product factors were most frequently mentioned as barriers to VR acceptability. Many participants reported concerns about the large size of the VR upon first impression, and some reported pain with VR insertion. Several participants reported concerns regarding cleanliness of the VR, particularly during menstruation. Relationship factors rarely appeared to act as barriers to VR acceptability; the majority of participants disclosed VR use to their sexual partners, and positive reactions from sexual partners regarding the VR were common. Emotional and/or physical discomfort surrounding VR use during sex was mentioned occasionally as a potentially barrier to VR acceptability.Relationship factors appear to be important in several populations for adherence to HIV-related medications. YMSM in high-risk sexual relationships may not modify PrEP-taking, leaving them at risk for HIV acquisition. Among serodiscordant couples, practical measures of partnership support may improve ART adherence and promote viral suppression. While adolescent girls most often reported that product-related factors inhibited VR acceptability, lack of partnership disclosure, negative partner reactions, and discomfort during sex may hinder VR acceptability among some girls.

Among Aboriginal people of Australia, diagnosis rates of sexually transmissible infections (STIs) are an example of the health disadvantage faced by this population. Diagnosis rates are between three and 50 fold higher than non-Indigenous Australians. Further there is a trend of divergence in HIV diagnosis rates, and in 2015 rates were more than double in the Aboriginal population than non-Indigenous rates. Despite much effort to reduce both incidence and prevalence of STIs in the Aboriginal population, there have been limited success. To contribute to addressing the gaps in research, this thesis examined both causes and impact of interventions to reduce STIs in this population. Chapter 1 is a review of STI epidemiology literature among Indigenous populations. Chapters 2 and 3 are papers from a national survey of 2,877 young Aboriginal people regarding sexual health. Chapter 2 describes the methods, implementation and demographics of the study. Chapter 3 is an analysis of this study, describing prevalence and correlates of participants who reported ever been diagnosed with an STI. Early sexual debut, inconsistent condom use and identifying as gay were significantly associated with a previous diagnosis. Chapter 4 describes Aboriginal peoples’ attendance, testing and positivity outcomes for chlamydia obtained from four primary health care settings. We found highest testing rates in sexual health clinics (80%) and lowest in general practice (5%) and higher positivity rates among Aboriginal people across all settings. Chapter 5 is an analysis of data from the STRIVE study, showing low rates of HIV testing (32%) conducted after a positive diagnosis for other STIs (n=15,260), demonstrating the need for improved clinical governance in this setting. Chapter 6 is a review paper assessing HIV prevention efforts among Aboriginal people in the first 25 years of the epidemic in Australia, and highlights the trajectory forward in prevention. The STRIVE Study Protocol is included in Chapter 7. This stepped wedge cluster randomised trial developed and implemented a sexual health quality improvement program in 68 remote communities with a primary outcome of reduced STI prevalence. Final results are currently being analysed. Finally Chapter 8 contains a number of recommendations directed at research, policy and programmatic levels that may address disparate rates of STIs and HIV in Aboriginal communities.

Despite the availability of highly efficacious antiretroviral drug regimens for the prevention of mother-to-child HIV transmission (PMTCT), transmission rates remain higher than those achieved in clinical trials. Access to these efficacious drug regimens continues to expand rapidly in countries most affected by HIV. Such expansion is an important first step in dramatically reducing mother-to-child HIV transmission rates. However, beyond access to drug regimens, programs must also identify and address individual and structural factors impeding the utilization of and adherence to PMTCT services by the women they are designed to serve. Additional research into factors both positively or negatively associated with PMTCT service utilization could help improve PMTCT programs to further reduce transmission rates. Each of the three papers included in this dissertation examined different factors of PMTCT service utilization. The first two papers analyze secondary data from a large-scale impact evaluation of Zimbabwe’s PMTCT program. Specifically, the first paper explores the association between costs (service costs, travel time, and transportation costs) and utilization of all recommended PMTCT services. The second paper explores the relationship between the timing of a pregnant woman’s HIV-positive diagnosis, either prior to pregnancy or during antenatal care, and her utilization of PMTCT services. The hypotheses was that women who were diagnosed prior to pregnancy, having had more time to cope with their diagnosis, would complete more of the recommended PMTCT services. The final paper utilizes policy analysis methodology to examine two different implementation strategies Malawi could consider to improve lifelong adherence to antiretroviral therapy (ART) among women living with HIV who initiate treatment during pregnancy or breastfeeding. The two strategies proposed were: 1) for all pregnant/breastfeeding women to initiate and indefinitely receive treatment at maternal and child health clinics rather than be transferred to an ART specialty clinic, and 2) to expand access to lifelong ART, regardless of stage of disease, to any individual living with HIV in the pregnant/breastfeeding woman’s household.

In comparison with high income countries, people living with HIV (PLHIV) in low income countries initiated Antiretroviral Therapy (ART) at lower baseline CD4 cell counts (median 108 versus 234 cells/mm3), leading to higher mortality (414 deaths during 20,523 person years of observation versus 124 deaths during 2,236 person-years of observation). In Vietnam, an estimated 62% of PLHIV initiate ART with a baseline CD4 ≤100 cells/mm3. The primary aim of this thesis is to investigate a range of factors that could be modified or implemented to improve the cost-effectiveness of ART in Vietnam. Specifically, it aims to explore current structural barriers to timely initiation of ART (Paper 1), identify the factors associated with timely ART initiation and key outcomes after six months of treatment (Paper 2), describe the trends in, and determinants of, loss to follow up (LTFU) and early mortality in HIV patients who initiated ART in the first five years of Vietnam’s national ART programme (2005-2009) (Paper 3), and investigate the cost-effectiveness of different ART expansion strategies that could be implemented in the ten year period 2009-2019 (Paper 4). This thesis is presented for examination as a thesis by publication, which means it presents a series of papers that were published in the peer review literature between 2010 and 2014, or submitted for editorial review to a peer reviewed journal prior to thesis submission, rather than the traditional model of presenting thesis chapters. In line with the requirements of the University of New South Wales (UNSW), preambles have been added to the papers to facilitate a coherent logic flow across the whole thesis, but they are otherwise unaltered from the published versions. Papers 1, 2, 3 are published and the specific citations are listed at the start of each chapter. Paper 4 is currently under editorial review. The introduction, and implications and future directions chapters, provide a broader context for the papers included in this thesis.

Cryptococcal meningitis (CM) is a wide-spread, yet under-recognized, fungal opportunistic infection occurring primarily among people living with advanced HIV/AIDS. While vast advances in understanding the pathogenesis and treatment options for CM have reduced mortality, major gaps remain in understanding factors that contribute to mortality rates of 12-20% in the first two weeks. The intent of this dissertation was to contribute towards the efforts to address these gaps and provide evidence that could further improve short and long-term recovery from HIV-associated CM in sub-Saharan Africa. The first paper was focused on mortality in the days after CM diagnosis and understanding whether lumbar punctures (LPs) to reduce intracranial pressure also reduce mortality. Raised intracranial pressure is common in CM patients and contributes to many of the disease's signs and symptoms. Two hundred forty-eight HIV-positive, CM patients from Uganda and South Africa were evaluated for the occurrence of therapeutic LPs and mortality within 11 days of CM diagnosis. Analysis was conducted using a marginal structure model, with time-varying exposure. The results suggest that undergoing at least one repeat LP reduced 11-day mortality by 69% (95% CI: 18% to 88%), adjusted for heart rate, CSF fungal burden and altered mental status. This beneficial effect was independent of the baseline CSF opening pressure, demonstrating that increases in intracranial pressure may be common among all CM patients and that all patients may benefit from an additional LP during initial therapy. The second paper was aimed at investigating baseline demographic and clinical features predictive of CM treatment success. The recommended initial treatment regimen for CM rapidly reduces infection; however, nearly 50% of CM patients will continue to have viable fungus in their central nervous system at the end of therapy. Being able to predict patientutcomes has many advantages including optimizing treatment for each patient and reducing drug toxicities. One hundred seventy-seven HIV-positive, CM patients undergoing 2 weeks of antifungal treatment, including amphotericin B and fluconazole, were evaluated for sterility of a CSF culture by the end of therapy. The baseline CSF quantitative fungal burden was a strong and practical predictor of achieving CSF sterility, along with the rate of fungal clearance over the first week of treatment, and the baseline hemoglobin. Information on the baseline burden of infection could be used to tailor the duration of treatment, thus avoiding unnecessary toxicity and treatment costs for individuals with a lower burden of infection and potentially shifting resources to allow for more aggressive treatment of high-risk patients. The third paper aimed to understand the consequence of residual fungal infection at the end of initial antifungal therapy in terms of mortality in the first weeks and months after 2-week therapy ends. Among 154 HIV-positive individuals surviving the initial 2-week phase of therapy, there was no evidence that either the presence or the amount of residual cryptococcal infection in the CSF had an association with mortality in the following 3 weeks or 6 months. It is possible that a higher dose of fluconazole used at the end of amphotericin therapy in the present cohort may have contributed to the lack of association. The objective of this dissertation was to expand the understanding of CM treatment and recovery in resource-limited settings. The results suggest that additional benefits could be gained from the use of therapeutic lumbar punctures during the acute phase of treatment, the possibility of customizing therapy to further reduce treatment toxicities, and, finally, describing the relationship between residual infection and CM mortality with indirect support for higher doses of fluconazole during subsequent phases of CM therapy.

Over the past decade, myriad social and economic factors have fueled a burgeoning population of people who inject heroin in sub-Saharan Africa, creating an urgent need for HIV prevention and treatment services tailored to this marginalized group. While the epidemic in the region remains largely driven through heterosexual risk behavior, a higher probability of disease acquisition per exposure can lead to rapid transmission among people who inject drugs (PWID). Stigma and discrimination isolates PWID from accessing available HIV care services designed for the general population and has contributed to HIV prevalence in PWID up to four times greater than country averages. To address this crisis, a few trailblazing governments with support from international HIV/AIDS funders have begun to develop and in the case of Tanzania, implement, comprehensive national harm reduction services for people who use and inject drugs. This dissertation contributes to the growing body of implementation science literature on medication assisted treatment programs (MAT) for PWID in sub-Saharan Africa. This dissertation takes a three-paper model to identify programmatic and policy strategies to enroll, retain and support patients in MAT programs, focusing on Tanzania. The first paper, a systematic review of the literature on methadone as an HIV prevention intervention, describes evidence-based best practices and applies key findings to make recommendations about service delivery in a limited resource setting. Results suggest that enhanced outreach and increased dosing can help maximize service utilization. The second and third papers delve into the experiences of the first MAT program on mainland sub-Saharan Africa, located at Muhimbili National Hospital in Dar es Salaam, Tanzania. The program has successfully implemented a continuum of harm reduction care, culminating in methadone treatment for PWID. However, monitoring and evaluation data highlight a gender disparity in service utilization, with women comprising less than 10% of clients. Relying on in-depth interviews and observational data collected over three field visits from July 2011 to February 2013, the last two articles look at ongoing service needs for women in treatment and identify strategies to bring more women into care. Results suggest that women face distinct hardship in treatment, needing increased psychosocial support services and economic development interventions to help them heal histories of sexual trauma and regain custody of their children. Additionally, outreach tailored to women can help increase treatment enrollment. Findings from this dissertation have implications for MAT programs in Tanzania and in other areas in the region with similar epidemiological and cultural environments.

The dissertation examines the experience of living with stigmatized health conditions in the social context. The first paper examines the dynamic, bi-directional relationship between social support and HIV-related stigma. I use data from a prospective cohort of people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy in rural Uganda. I use multilevel regression to model the contemporaneous and time-lagged relationships between two dimensions of stigma and social support. The results suggest that the two dimensions of stigma may compromise the ability to maintain and access social support. I also found that social support may be protective against future experiences of discrimination. The second paper examines the trajectory and determinants of health-related quality of life (HRQOL) of PLWHA initiating antiretroviral therapy. Using the same data set as paper one, I compared two types of multilevel models for change in which HRQOL is specified as linear and quadratic functions of time. Analyses indicated that HRQOL follows a quadratic trajectory that is concave to the time axis. Self-reported symptoms, food insecurity, and HIV-related stigma are negatively correlated with HRQOL, suggesting the importance of addressing social and economic situations of PLWHA in addition to clinical symptoms. The third paper is an interdisciplinary review of health-related stigma. The social psychology literature describes stigma as a product of individual traits and personalities that has roots in the biological instinct to avoid poor partners of social exchange. In contrast, the historical, anthropological, and autobiographical literatures highlight the role of social forces outside of the individual in the production of stigma. I argue that health-related stigma is based on the ever-changing understandings about disease causality that reflects contemporary ideas about morality. Further, stigmatization is contingent on a social structure in which differential access to social, economic and political power determines who is stigmatized. Finally, stigmatization dehumanizes individuals who are already vulnerable, and erects barriers to health and social resources to further exacerbate social inequalities. Therefore, health-related stigma should not be used as a tool to promote public health, and societal efforts should focus on eliminating health-related stigma.

This paper examines the impact of spatial variation in HIV rates on female marriage rates in Zambia. I formulate a search model that predicts lower marriage rates of educated females relative to uneducated females in regions with higher HIV rates. I use exogenous geographic variation in HIV rates to identify the causal effect of HIV on female marriage. The risk of HIV infection causes marriage rates to fall for educated females but rise for uneducated females. One explanation is that in high HIV regions: (1) educated females take the time to find a partner who will use condoms and get HIV tested, which delays marriage, and (2) uneducated females marry sooner because youth and virginity are prized by males, and employment opportunities are scarce. These findings imply that returns to education for young females are likely underestimated since they miss conceivably substantial health-related benefits. Is widow remarriage beneficial to child school enrollment? Women are widowed at relatively young ages in high-HIV areas of Sub Saharan Africa and are likely to have school-aged children. A main finding in the parental death literature is that the death of a mother hurts child education more so than does the death of a father. This masks important differences in child school enrollment across households who have experienced a father's death. This paper estimates the effect of widow remarriage on child school enrollment by exploiting regional variation in HIV, religion, and the sex ratio. The cross-country empirical results indicate that remarriage is detrimental to child enrollment for widows with less than six years of schooling, yet beneficial to child enrollment for widows with six or more years of schooling. This is consistent with (1) marital sorting by education (correlation=.7), (2) intra-household bargaining, and (3) differences in tastes for remarriage and schooling. A policy implication is that investing in female education in high-HIV areas - among those likely to become widows - can have multiplier effects, as there is complementarity between the returns to education on marriage market outcomes and children's education.

Abstract: Over the past three decades, the HIV epidemic has gained a stranglehold in sub-Saharan Africa, where 10% of the world’s population comprises more than 60% of all people living with the disease. Recent initiatives to boost prevention and treatment interventions are beginning to yield modest but promising results, as infection rates slowly start to stabilize. However, continued improvement will require aggressive and unrelenting efforts to prepare and equip a workforce for the tremendous challenges that remain. The purpose of this critical ethnography was to explore the impact of an intensive 6-month HIV/AIDS education program on the lives of 24 Ugandan registered nurses and nurse-midwives who worked at a large referral hospital. The study began following completion of the course and involved participant observation and semi-structured interviews for 18 weeks over a 2-year period. The findings are presented in this dissertation, which consists of four published or publishable manuscripts along with introductory and concluding chapters. The first paper describes the impact of education on the personal, professional, and social lives of the participants, and provides an account of their new ways of viewing themselves as nurses, leaders, and advocates. The second paper addresses ethical issues concerning the conduct of research in international settings. The third paper identifies the phenomenon of moral distress as it manifested in the participants, and the effects of education on their ability to transform practice and attitudes. The final paper examines the congruence between the critical qualitative methodology used in the study and the concept of cultural safety in the context of international nursing research. The dissertation concludes with a discussion of the crucial role of continuing professional education for the development of a strong and responsive nursing workforce that is prepared to contribute leadership and vision to addressing the obstacles presented by HIV and AIDS. Dealing effectively with the epidemic requires numerous interventions at various levels; the potential synergies offered by a small investment in education may have far-reaching effects. Finally, implications for nursing practice are presented along with suggestions for further research.

Sex education policies and programs in Florida are largely dominated by the abstinence-only approach. This paper makes the case that abstinence-only education is a failing policy in Florida, and evaluates strategies advocates may use in order to accomplish reform. Three different strategies are evaluated: countywide school district reform, statewide rejection of federal abstinence-only funding, and statewide standardization of sex education via legislation. Contrasts are drawn between all three strategies with regard to their potential impact on sex education policy in Florida, viability, and the challenges they present to advocates. This paper concludes that statewide standardization of sex education in Florida represents the best way to remedy the problem of insufficient sex education, but is unlikely to occur without increased bipartisan support in the Florida legislature. Statewide rejection of Title V federal abstinence-only funds remains an important policy goal for the purpose of accomplishing an end to federal abstinence grants but would likely achieve very little for Florida's students. Countywide sex education changes are thus far the only substantive victory for sex education advocates in Florida and should be instituted across the state with advocates taking special care to engage teachers, medical professionals, parents and local community leaders.

It is well documented that Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome (HIV/AIDS) disproportionately affects Hispanics and Latinos in the United States (US). While Hispanics represented 17% of the US population in 2014, they accounted for nearly one-fourth (23%) of all new estimated HIV diagnoses. Furthermore, Hispanics/Latinos made up nearly one-fifth (21%) of all persons living with HIV infection in the United States (and six dependent areas). Hispanic/Latino populations face numerous barriers that negatively impact their outcomes along several steps of the HIV care continuum. This paper will discuss the HIV care continuum, particularly focusing on disparities that Hispanic and Latino populations may face progressing through several steps of the continuum. Furthermore, a focus on defining barriers that this population may face accessing and maintaining regular HIV care will be used to explore ways that providers can deliver culturally tailored, appropriate HIV care to this population. An emphasis on the social determinants of health on the HIV outcomes of Hispanics/Latinos will be crucial in addressing the disproportionate share of the HIV burden that this population encounters.

In this paper, the author uses country-level educational enrollment data parceled into primary-, secondary-, and tertiary-attainment, to delineate connections with specific development outcomes in low- and middle-income countries. The analyses are conducted using OLS Regression to assess education’s impact on total fertility rate, HIV prevalence, under-five mortality rate, life expectancy, GDP per capita growth rate, and the proportion of women in parliament. The author found that the levels of educational attainment have differentiated impacts on the development outcomes tested with secondary attainment having the strongest relationship to the total fertility rate while tertiary attainment has the strongest relationship of the attainment variables to under five mortality rate, HIV prevalence, and life expectancy. These results provide information for policy-makers looking to improve various indicators of wellbeing in their country.

The Botswana HIV/AIDS epidemic started in the early 1990s, with the proportion of the overall population infected with HIV (prevalence) rapidly escalating to 28.2% by the year 2000. Today, HIV prevalence has decreased to 23%, yet Botswana has the third highest percentage of HIV infected population in the world. The HIV epidemic in Botswana is in need of attention, but prevalence alone does not represent the full picture. HIV incidence (the rate of new infections and a critical indicator of success of HIV prevention programs) peaked in Botswana around 1996 at 5.7% and has declined to about 2.72% today. Botswana's two most effective programs in its response to the epidemic have been provision of universal HIV treatment and prevention of mother-to-child-transmission (PMTCT) programs, which have achieved over 95% coverage for all eligible patients. These two programs largely account for Botswana's rapid decline in HIV prevalence and incidence rates. However, females have continually had higher rates of prevalence and incidence than males throughout the course of Botswana's epidemic. In order to continue these declining rates of infection, Botswana may consider redoubling its efforts around HIV prevention. Women and young adolescent girls have not been the main beneficiaries of prevention programs. Women are more susceptible to HIV infection biologically and more vulnerable to infection due to social determinants, most notably their lack of empowerment and control in sexual partnerships. The main social drivers of the HIV epidemic in Botswana have been concurrent partnerships, sexual assault, cross-generational sex, and transactional sex. These drivers increase risk of HIV infection particularly for women. Botswana has implemented promising national prevention programs focused on HIV counseling and testing, consistent condom use, decreased concurrent partnerships, and male circumcision. However, the Botswana legal system reinforces gender inequalities, further increasing women's risk for HIV infection. In Botswana's law, martial rape, domestic violence, and intimate partner violence are not criminalized. Further, sex with minors and sexual assault are not strictly enforced. Sex work is illegal and stigmatized, and thus sex workers are not receiving appropriate support in HIV prevention. This high-risk population accounts for only 1.65% of the general population but will account for 6.38% of new HIV infections. The HIV treatment and PMTCT programs have decreased HIV incidence, but Botswana may consider increasing its behavioral prevention programs to regard gender norms and reforming legislation to protect women and young girls. This paper recommends behavioral prevention programs through increased youth education programs, women empowerment programs, access to sexual and reproductive health care, and male involvement in sexual and reproductive health. Further, it is recommended that policy makers focus on reforming civil legislation and bolstering enforcement of existing laws that protect women from violence. The key to successful scale-up of behavioral prevention in Botswana will be community-driven HIV initiatives and strong leadership from community leaders and members of parliament, including women.

Mounting evidence that the global climate is changing has motivated a growing body of work seeking to understand the likely impacts of these changes on economic outcomes of interest. This dissertation studies the effects of variation in climate on three different outcomes: agricultural productivity in the United States, HIV in Africa, and human conflict around the world. Along with the co-authors on these papers, I find that both short- and long-run increases in temperature are harmful to agricultural productivity in the US, that increased exposure to drought increases HIV prevalence in rural parts of Africa, and that increases in temperature and extreme rainfall are associated with substantial increases in a variety of types of human conflict. These findings have implications both for our understanding of the economics of disease and conflict, and for how much societies might be willing to invest in emissions mitigation and adaptation in the face of future climate change.

As an epidemic in the increasingly image-conscious and media-driven twenty-first century, the course of HIV/AIDS has been shaped by both mass media's portrayal of the disease and public perception of it. Russia currently has the highest HIV infection rate outside of Sub-Saharan Africa. In St. Petersburg, HIV infection rates are continuing to rise---the primary mode of transmission is changing from Injection Drug Use (IDU) to heterosexual intercourse, and fastest growing age group of infected persons is 30-40. As the epidemic begins to spill over from IDUs and homosexual communities into the general population, new attitudes are arising within St. Petersburg society and mass media. This paper analyses the role of mass media in HIV/AIDS prevention campaigns around the world, before presenting the author's research on the effects of mass media presentations of HIV on the St. Petersburg population. Through a three-part research study involving in-depth interviews, qualitative surveys, and a media analysis, the author portrays the media landscape in St. Petersburg in 2013 with an eye towards resolving media agendas, government policies, and public attitudes.

This study examined household food security (HFS) and physical activity (PA among individuals living with HIV/AIDS living in rural Appalachia (West Virginia, Appalachian Ohio, Kentucky, and Pennsylvania). Participants (n = 82) completed an online or paper survey that included validated measures of HFS (USDA short form) and physical activity. Data were analyzed using PASW statistical software (version 18.0,) to determine the relationship between the variables (Mann-Whitney U). The majority of participants (n = 82) were: male (n = 63) and Caucasian (n = 59). For all patients, 28 (34.1%), 10 (12.2%), 12 (14.56%), and 32 (39.0%) were living in households characterized as being high, marginal, low, and very low HFS, respectively. There was no significant difference in distribution of IPAQ scores (Mann-Whitney U, p = .161), and total MET-min per week of physical activity between the HIV and AIDS groups (t-test, p = 0.200). There was no significant difference between distribution of IPAQ scores (Mann-Whitney U, p = 0.929), and total MET-min per week (t-test, p = 0.944) between food security groups. Further exploration is warranted in other rural regions.

Outcomes for children depend importantly on parental decisions regarding inputs. This relationship is perhaps most obvious in developing countries where families face liquidity constraints and income uncertainty. To better understand potential risk sharing mechanisms within the household, I first present theoretical evidence of the relationship between a parent’s risk aversion and child quality in the context of a collective household model. I then estimate the effect of an experimental measure of risk aversion on a child’s well-being using the Mexican Family Life Survey. I find that a mother and father’s risk aversion increase investments in male children and decrease investments in female children, which is consistent with the patterns of old age support in Mexico.In my second chapter, I examine whether HIV testing leads to revisions in the subjective likelihood of being HIV positive as well as the likelihood of surviving across various time horizons. This study is based on the Malawi Diffusion and Ideational Change Project (MDICP), which allows me to use randomized financial incentives as instrumental variables for the decision to learn one’s HIV status. I find that women who learn their HIV negative status believe they are negative at the time of testing but appear to overestimate their likelihood of having contracted HIV in the two-year period after learning their HIV status. My third chapter examines the relationship between learning one’s HIV negative status and decisions made within households in the MDICP. Using the financial incentives as instrumental variables for the decision to learn one’s HIV status, we find that there is no effect on marital stability two years after a woman learns her HIV negative status, but that the marriage is less likely to stay intact if the husband discovers he is HIV negative. We also find a significant increase in the share of expenditures that are spent on children's schooling and a decrease in the share spent on children's medical expenditures. This paper illustrates that HIV testing can be an effective policy tool for increasing the incentives to invest in children’s welfare and human capital.

This dissertation combines three studies from East Africa, each investigating a different way in which individuals respond to institutional changes, and how this response shapes the broader impact of these policy levers. Each paper develops and explains one or more theories of individual behavior and combines data from a wide range of sources to test hypotheses generated from the original theories.The first chapter measures the impact of provision of ARVs on risky sexual behavior among young women in Kenya, and estimates how this response will shape future HIV infection rates. Access to antiretroviral (ARV) drugs in Sub-Saharan Africa has rapidly expanded - from fewer than 10,000 people treated in 2000 to more than 8 million in 2011. To measure the impact of this expansion, it is necessary to identify the behavioral response of individuals to drug access. This chapter combines geocoded information about the timing of introduc- tion of ARVs in all Kenyan health facilities with two waves of geocoded population surveys to estimate the impact of proximity to an ARV provider on risky sexual behavior. Using a difference in differences strategy that matches survey clusters geographically across waves, I find a relative increase in risky behavior as reflected in pregnancy rates (increase of 82%) and self-reported recent sexual activity (increase of 40%) among young women in areas in which ARVs were introduced between 2004 and 2008. The full impact of ARV access on new infections is estimated through a simulation procedure that combines estimated behavioral responses to ARVs with medical evidence regarding HIV transmission. An increase in ARV drug access is predicted to reduce the rate of new infections despite the induced increase in risk-taking.The second chapter looks at the impact of corruption on the effectiveness of antiretroviral drugs in preventing deaths due to HIV and the potential channels that generate this relationship. This is based on a unique panel dataset of countries in sub-Saharan Africa, which combines information on all imported antiretroviral drugs from the World Health Organiza- tion's Global Price Reporting Mechanism with measures of corruption and estimates of the HIV prevalence and the number of deaths in each year and in each country. Countries with higher levels of corruption experience a significantly smaller drop in HIV deaths as a result of the same quantity of ARVs imported. This is followed up with a single case-study from Kenya to illustrate one potential mechanism for the observed effect, demonstrating that disproportionately more clinics begin distributing ARVs in areas that are predominantly represented by the new leader's ethnic group.The third chapter uses new data on participation to examine how local economic conditions shaped within-country variation in willingness to participate in violent activities during the Rwandan genocide. It discusses and tests the predictions of three sets of theories about the causes of violence. The data provide strong evidence that higher rates of both unemployment and education among Hutu are associated with increased participation. I find no evidence that the employment or education of the Tutsi population reduce participation rates. I also find suggestive evidence of a positive association between violence and the interaction of Hutu unemployment and education both at the commune level and at the individual level. These results are consistent with theories of opportunity costs discouraging violence, and they provide additional evidence of a connection between education, unemployment, and violence.

HIV is a virus currently affecting approximately 33.3 million people worldwide. Since it's discovery in the early 1980s, researchers have strived to find treatment that helps the immune system eradicate the virus from the human body. A great deal of advances have been made in helping HIV infected individuals from advancing to AIDS, but no cure has yet been found. Researchers have found that the immune system is in a chronic state of activation during HIV infection and believe this could be a major contributor to the decline of immune system cell populations. Using analysis of systems of Ordinary Differential Equations, this paper serves to better understand the dynamics of the activated immune system during HIV infection. Both current and possible future therapies are considered.

Abstract: There is a real relationship between the HIV/AIDS pandemic and the world of work. The complexities in the relationship are strengthened by the long asymptomatic period of the disease and its significant presence among a certain age group that forms a major part of the work force. The presence of HIV/AIDS in a workplace, if not effectively managed, leads to unpleasant effects such as an increase in the cost of production, which translates into income loss and capital depletion. Superficial knowledge of these factors often makes the workplace hostile and leads to a culture of discrimination in which the well-being and rights of those affected by the virus are either undermined or out rightly ignored. An effective way of mitigating these negative effects is the provision of workplace reasonable accommodation measures. This paper proposes pragmatic legal ways of meeting the reasonable accommodation needs of people living with HIV/AIDS in Canada.

For decades, medical perspectives have dominated the literature studying HIV/AIDS. More recently, issues related to HIV concerning the behavioral and psychological well-being of persons with AIDS (PWA) have surfaced. Much of the research in this field focuses on the coping strategies of PWA as they relate to the race, gender, and age of the infected individual. Additionally, studies examining how families cope with HIV focus on family functioning and caring for PWA. Still missing from this literature however, is an understanding of the different ways in which PWA cope with their illness, and how they come to use particular coping strategies. This paper examines the ways in which individuals cope with HIV. I speculate that the mode of transmission will influence the mechanisms individuals use cope. For example, individuals who contract HIV from a blood transfusion will use coping strategies that are different from an individual who has contracted HIV from having shared infected needles or from having sexual relations with members of the same sex. I link this difference in coping to the different kinds of stigma attached to these behaviors. This study finds that coping with HIV is complex and takes many forms. The men in this study use a variety of coping strategies, often at the same time. Social support and stigma are particularly important in the choosing and implementation of particular coping strategies. I argue that because coping takes many forms, we need to approach coping as not always being only “active” or only “passive”. Doing so will allow a better understanding of coping as it relates to stigma and social support.

The main goal of this study, in the field of the Anthropology of Policy, was to analyze the social construction of the AIDS vulnerability of truck drivers in the South of Brazil, examining the national HIV/AIDS prevention policies. The discourse of three social actors were analyzed using the Medical Anthropology framework: (i) the national gonvernmental AIDS agency, (ii) the Non Governmental Organizations supported by the National AIDS Program to execute prevention projects targeting truck drivers, and (iii) the truck drivers themselves, passing through Rio Grande do Sul state. Three important themes traverse this study: (i) globalization (and the global/local relations), (ii) the identity of a social group or a community, and (iii) the construction of a sexual culture. To understand the social construction of the truck drivers’ vulnerability, I followed the route that this idea went through different institutions and levels. Beginning at international intergovernmental agencies such as the World Health Organization, the United Nations AIDS Program (UNAIDS) and the World Bank, the course followed through the analysis of scientific research on the theme, and finally the national AIDS agency’s discourse. The route finally came to how NGOs seize and use the idea that truck drivers are a vulnerable group, ending with how the truckers themselves perceive their vulnerability to HIV, AIDS and sexually transmitted infections. The study was limited in scope by the action of NGOs who had developed publicly funded projects targeting truck drivers. Methodologically, the study collected and analyzed data of different origins, types and qualities. Official documents, grey literature, scientific papers on truckers and HIV/AIDS, as well as NGO project proposals were studied. Data collection also involved an ethnography and a survey (N=854) of truck drivers. Both qualitative and quantitative studies of truckers were developed in Rio Grande do Sul, southernmost state of Brazil, in the cities of Porto Alegre, Gravataí, Canoas, Rio Grande and Chuí. Truckers are immersed in a social network, both in the truck stops (fuel stations and customs) and in their places of origin (where family relations prevail). The social universe of the truckstops is not a simply a transitory place: there are rules of conduct, leaderships, social spaces which are symbolic and geographically marked, and a number of persons who maintain diverse relations amongst themselves for a long time. Truck drivers did mention inconsistent use of condoms, specially with regular or fixed partners, that certainly increases their vulnerability to HIV and sexually transmitted infections. However, inconsistent condom use, and the availability of commercial sex workers, is not exclusive to truckers or truck stops. Emphasis is given to the programmatic or institutional vulnerability of truck drivers.

The study of attitudes towards those with AIDS is relatively recent. Most studies have examined attitudes concerning health and medical concerns. Little research has focused on attitudes toward social and behavior concerns. The few that have focused on such attitudes have employed relatively small samples collected primarily out of convenience. The studies that have used national samples have primarily addressed public policy issues. Using national data from the 1988 General Social Survey, this paper examines the effects of personal knowledge about the AIDS virus and other attitudinal variables on four dimensions of social and behavioral concern for those with AIDS in American society. Sociodemographic variables, which prior studies have demonstrated as important predictors of attitudes toward AIDS, are included as controls in this research that presents findings from a multivariate analysis. Results suggests that the impact of personal knowledge of someone with AIDS does not strongly lead to more supportive attitudes regarding the rights of people with AIDS, except when the economic costs of AIDS care is concerned. Directions for future research are presented and discussed.