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.

These studies aimed to build prediction models for cardiovascular-related outcomes among people living with HIV and compared model performance with previous standard models. The three outcomes were new subclinical atherosclerotic plaques, all-cause mortality, and non-HIV mortality. The two standard models for comparison were the pooled cohort equations (PCE) and the Veteran Aging Cohort Study (VACS) Index. We used the MACS/WIHS Combined Cohort Study to build each model in the whole data and separately as sex-specific models. During the model building process, we incorporated machine learning techniques, including the elastic net regularization and the boosting ensemble approach, for better prediction. The results from the three studies point in the same direction that the new model offers better predictive performance than the previous benchmarking models. However, only the 10-year sex-specific models and the 10-year MWCCS model for all-cause mortality satisfied all the performance measures and would be recommended to further pursue external validation.

Background: Tuberculosis (TB) is one of the top ten causes of death by a single infectious agent. Extensively Drug-Resistant TB (XDR-TB) is a type of MDR TB, defined as TB resistant to at least isoniazid and rifampicin, plus any fluoroquinolone and at least one of three injectable second-line drugs. XDR-TB is considered a significant public health threat in Thailand because of the rising of reported XDR-TB cases, the more financial burden for both patient and provider sites, and more adverse events in XDR-TB treatment. This dissertation examines the biopsychosocial factors, such as a) whether non-adherence to the MDR-TB treatment regimen is a leading cause of development to XDR-TB, b) which NAT2 diplotype or HLA class 2 alleles associated with XDR-TB cases, c) the pattern of initial culture conversion in XDR-TB group while on MDR-TB treatment compare to MDR-TB group.

Methods: We conducted a matched case-control study and recruited all secondary XDR-TB cases that were reported to the Bureau of Tuberculosis from October 2014 to June 2019. A total of 45 secondary XDR-TB cases were enrolled at 32 original hospital sites, across 29 provinces in Thailand. MDR-TB controls were randomly selected from the same hospital, where XDR-TB cases were treated. The proportion of cases to controls was one XDR-TB to two MDR-TB matched by geographical region. In the first two studies (Chapter 2-3), nine of 45 secondary XDR-TB cases died before we started. Then, only 36 XDR-TB cases and 75 MDR-TB controls were available for interviews and genetic tests. The conditional logistic regression was used to assess the magnitude of the non-adherence effect. Fisher exact test and conditional logistic regression were also used to explore the association between NAT2 diplotype, HLA class 2 alleles, and XDR-TB cases. In the third study (Chapter 4), we could not find the record of sputum culture in seven of 45 secondary XDR-TB cases. We used Cox proportional hazard regression for the difference in time to initial culture conversion in 38 XDR-TB cases and 76 MDR-TB controls. We also used the sensitivity and specificity of initial culture conversion at the beginning of MDR-TB treatment to 15-month in the prediction of the XDR-TB susceptibility and MDR-TB treatment outcome.

Results: We found that patients with non-adherence while on MDR-TB treatment were ten times more likely to develop XDR-TB (AOR 10.08, 95%CL 1.36, 74.87) while adjusted for type of Directly Observed Treatment, age, gender, socioeconomic status, and harmful alcohol use which was less than the magnitude from improper regimen (AOR = 26.89, 95%CL 7.39, 97.81) while adjusted for culture sending and region. For the genetic study, NAT2*4/5B (OR 3.9, 95%CI 1.2 13.0) and the heterozygosity of HLA-DRB1 16:02 were about four times associated with XDR-TB cases (OR 3.7, 95%CI 1.2, 11.9). None of the associations was found in HLA DQB1. For the third study, the improper regimen for MDR-TB treatment was found to significantly reduce the chance of initial sputum culture conversion (aHR 0.24, 95%CL 0.15, 0.38) adjusted for wrong drug administration and dosage, and follow-up sputum culture. Furthermore, positive culture at the end of four-month of treatment was a good predictor for failure outcome (sensitivity 67.7%, specificity 93.8%) and the development of XDR-TB (sensitivity 63.2%, specificity 94.7%).

Conclusion: The main factor that causes XDR-TB was not non-adherence; the more significant factor was improper regimens for MDR-TB treatment, which mainly came from the provider site. From the aspect of host genetic, the result of this study was found significant in NAT2 *4/5B and heterozygosity of HLA-DRB1 16:02. There was no clinically significant for NAT2. However, HLA-DRB1 16:02 is associated with acquired immunodeficiency that can make the host more likely to develop XDR-TB. For the follow-up of sputum culture conversion, the improper MDR-TB treatment regimen also played a significant role in reducing the chance of sputum culture conversion. Also, the lack of sputum culture conversion at month four would give us the best prediction for the development of XDR-TB. Overall, the finding from these three studies suggested the probable risk and protective factors of XDR-TB. From a policy perspective, further work is needed to examine the impact of the new DR-TB guidelines on the actual MDR-TB treatment regimen and assess the effectiveness of the treatment audit system when it starts.

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Introduction: Myanmar has prioritized HIV testing services and prevention of mother-to-child transmission of HIV services to reach the milestone - 95% of people living with HIV know their status and eliminate mother-to-child transmission of HIV. Many people living with HIV had late diagnoses for HIV in many countries in the Southeast Asian region. This study assessed HIV testing and its associated factors among women aged 15-49 years in Myanmar and other selected Southeast Asian countries - Cambodia, the Philippines, and Timor-Leste.Methods: Multivariable logistic regression analyses were performed using the 2015-16 Myanmar Demographic and Health Survey (DHS) data to determine factors associated with lifetime HIV testing uptake by marital status and having an HIV test as part of antenatal care (ANC) among women in Myanmar. A comparative analysis of the four selected countries was conducted using data from the 2015-16 Myanmar DHS, the 2014 Cambodia DHS, the 2017 Philippines DHS, and the 2016 Timor-Leste DHS to assess lifetime HIV testing and associated factors among women. Literature review and the conceptual framework adopted from Anderson’s Behavioral Model of health services guided the inclusion of potential predictors in this study. Results: The proportions of lifetime HIV testing among women aged 15-49 years were significantly varied by marital status in Myanmar. Poorest wealth index, living in rural areas, lack of comprehensive knowledge of HIV, having < 4 ANC visits, and no counseling on HIV during ANC were negatively associated with having an HIV test as part of ANC in Myanmar. Lifetime HIV testing rate was highest in Cambodia and lowest in Timor-Leste. Marital status, education level, wealth index, places of residence, and comprehensive knowledge of HIV were significantly associated with lifetime HIV testing uptake among women in all selected Southeast Asian countries. Conclusion: Health education campaigns for HIV should target women and adolescent girls to increase comprehensive knowledge of HIV. Effective integration of HIV testing services to related healthcare services, and tailoring HIV testing services to rural communities and youth, financial assistance, and a multisectoral approach for creating more educational and employment opportunities are needed to reduce gaps in HIV testing among women.