Graduation Date

Spring 5-8-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Epidemiology

First Advisor

Dr. Lorena Baccaglini

Second Advisor

Dr. Christine M. Arcari

Third Advisor

Dr. Howard Fox

Fourth Advisor

Dr. Christopher S Wichman and Dr. Jane Meza

Abstract

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) persists in people living with HIV (PLWH) with clinical and public health implications. Studies have generated inconsistent results regarding etiological factors for NCI in PLWH and a brief user-friendly predictive tool is desirable in clinical practice to assess the probability of having NCI in PLWH. Furthermore, factors associated with clinically meaningful decline in neurocognitive status and survival disadvantage for patients with NCI are understudied in the post-cART era. The goal of this dissertation was to investigate factors associated with baseline NCI and neurocognitive decline and the association of baseline NCI with mortality in PLWH. Further, we aimed to construct a predictive tool for NCI and to examine the association between longitudinal changes in neurocognitive status and mortality in PLWH. We used two large databases, the National NeuroAIDS Tissue Consortium (NNTC) and the CNS HIV Antiretroviral Therapy Effects Research (CHARTER), to carry out this research project. Statistical procedures such as Bayesian network analysis, multiple logistic regression, joint modeling, and multivariable Cox proportional hazards modeling were employed.

Results of first study indicated that neurocognitive impairment had positive associations with older age, current unemployment, difficulty in bathing, dressing, eating, or using the toilet, impaired use of hands, history of high cholesterol, current psychotropic medication use, presence of any AIDS-defining illness and lifetime history of stroke. In the second study we noted that lifetime depression, hepatitis-C infection, lifetime methamphetamine and cannabis use Hispanic ethnicity, no baseline ARV use, and difficulty eating, dressing, bathing, or using the toilet were positively associated with neurocognitive decline. Finally, the third study exhibited a significant interaction between age and neurocognitive status in relation to mortality. Also, non-Hispanic ethnicity, lower baseline serum hemoglobin and higher baseline plasma viral load were positively associated with higher hazard of death. By knowing associated factors, the results of this study could assist clinicians identify patients needing comprehensive neuropsychological examination resulting in timely diagnosis and appropriate management. Furthermore, through targeted interventions, the results of this study may assist in improving the quality of life and disease outcomes (decline and mortality) among PLWH.

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