Mentored Scientist Award

Tuberculosis (TB) is the leading cause of death in HIV-infected people in sub-Saharan Africa. Intermittent or shortened TB therapy in patients with HIV leads to poor outcomes, but the duration of TB therapy - 6-8 months for drug-sensitive disease - makes it logistically challenging in low-income countries. A reliable marker of TB treatment response could improve outcomes by identifying patients likely to fail or develop drug resistance early. In addition, it could speed the development of more potent drug combinations that would shorten therapy.

Atherosclerosis is more common in HIV-infected individuals and manifests at an earlier age. Loss of endothelial cell (EC) function increases the cardiovascular risk. A key vasoprotective molecule released by healthy endothelium is nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS).

Objective: To determine if and how NO bioavailability is altered in ECs of HIV-infected subjects on virally suppressed therapy.

HIV-related sexual risk behavior is commonly ascertained by collecting retrospectively enumerated sexual activities that span 3-month or 6-month periods. This approach is problematic because of recall bias, potentially leading to underreporting of key behaviors. We propose to design, and determine feasibility and acceptability, and validity of a novel sexual health-oriented mobile health (mHealth) application (app) to assist with daily reporting of sexual activities and thereby eliminate the problems associated with recall bias.

Objective: The purpose of this study is to investigate whether there is an association between HIV infection and atrial fibrillation (AF), the most common cardiac arrhythmia. Despite the importance of AF and its associated morbidity and mortality, the incidence, treatment and outcomes of AF in the setting of HIV infection have never been formally studied.

Millions of HIV-infected Africans now receive life-saving antiretroviral therapy (ART). However, mortality remains high, and persistent immune activation during early ART-mediated viral suppression is an independent predictor of mortality in this setting. Studies have shown that generalized immune activation accelerates clinical progression of untreated HIV disease, persists during therapy, predicts poor immune recovery during suppressive ART, and may lead to increased mortality. One potential inflammatory pathway mediating morbidity and mortality is the tryptophan oxidative (TOx) pathway.

Uganda has one of the highest per capita rates of alcohol consumption in the world coupled with a generalized HIV epidemic that affects 5-7% of the adult population. A growing body of research has shown that alcohol use is strongly correlated with sexual risk behavior, but the strength of this association among HIV+ adults remains unclear. Understanding the mechanisms by which alcohol use is related to unprotected sexual intercourse among HIV+ individuals is essential for developing effective secondary HIV prevention interventions.

Interventions are increasingly sensitive to the role of social networks and cultural dynamics on behavioral change, reflecting a shift in the focus of prevention strategies from individuals to communities. This study addresses the contextual issue of relationship power in young injection drug users (IDU), an at-risk population for HIV, hepatitis C virus (HCV) and other blood borne pathogens.

In high burden countries, isoniazid preventive therapy (IPT) is recommended for all HIV-infected individuals for whom active TB is deemed unlikely. However confident exclusion of active disease is required prior to initiation of this life-saving intervention. Although the highly sensitive WHO four-part symptom screen effectively rules-out active TB for those who screen-negative, up to two-thirds of HIV-infected individuals screen-positive and are therefore misclassified as ineligible for IPT.

With modern antiretroviral therapy (ART), HIV-infected individuals can now achieve durable viral suppression. Despite this, they continue to have higher rates of many chronic conditions including coronary artery disease and other cardiovascular conditions ^2,5 . Persistent immune activation and inflammation, likely mediated by ongoing HIV RNA replication and/or release in lymphoid tissues and persistent microbial translocation ⁶ , are strong predictors of these complications and have been proposed as important mediators of increased cardiovascular risk ⁷ .

As the HIV-infected population ages, it is critical to understand how geriatric principles can be applied to improve outcomes and quality of life for older HIV-infected adults. Geriatric syndromes, which include falls, incontinence, and cognitive impairment, are a fundamental construct in gerontology. These syndromes are the result of deficits in multiple organ systems, as well as psychosocial and environmental vulnerabilities.