Mentored Scientist Award

Tuberculosis (TB) is the leading cause of mortality in people living with HIV. To reduce the burden of disease, a non-sputum biomarker-based diagnostic for tuberculosis (TB) is urgently needed. Urine-based testing is promising, but current assays that detect the Mycobacterium tuberculosis (MTB) antigen lipoarabinomannan (LAM) have poor performance and are only recommended in HIV-infected individuals who are severely ill or have advanced AIDS. There is a need to improve the sensitivity of these assays, and for approaches to detect other low abundant TB biomarkers in urine.

Antiretroviral therapy (ART) has transformed HIV into a chronic disease, dramatically extending the lifespan of people living with HIV (PLWH). As such, the burden of cardiovascular disease (CVD) in PLWH is expected to increase significantly as the current generation ages. PLWH have been shown to be at increased risk for CVD, including sudden cardiac death, acute myocardial infarction, stroke, peripheral arterial disease, and heart failure. The mechanism of elevated risk of CVD in HIV remains unknown, but chronic inflammation is suspected to play a role.

Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV) worldwide. Improving the diagnosis and treatment of TB in ‘high-risk’ groups will be critical to the Global End TB strategy. It is not well appreciated that men account for two-thirds of the 9 million new adult TB cases globally. Similar to PLHIV, men represent a high-risk TB population as they are also more likely to develop TB, remain undiagnosed, and experience poor TB-related outcomes.

Despite combination antiretroviral therapy (cART), HIV persists as an integrated provirus in latently infected cells, preventing cure. Recent work in our laboratory suggests that HIV latency in circulating CD4+ T cells is likely due to a series of reversible blocks to HIV transcriptional elongation, distal transcription/polyadenylation, and especially splicing.

In the United States, nearly a third of those diagnosed with HIV were diagnosed late, meaning that they were diagnosed with AIDS at the same time as or within one year of their HIV diagnosis. Late HIV diagnosis is associated with poor treatment outcomes and, in turn, less viral suppression, greater transmission of HIV to those who are not infected, and increased HIV-related morbidity and mortality. The United States’ goal of reducing HIV in part by increasing peoples’ awareness of their HIV status cannot be achieved without addressing late diagnosis.

Prevention of mother to child transmission of HIV is now possible through evidence-based strategies that reduce the risk of transmission to less than 2%. However, the effectiveness of these strategies depends on the mothers living with HIV adhering to HIV treatment and being retained in care. Difficulties in adhering to prevention strategies has resulted in mother to child transmission (MTCT) rates that remain unacceptably high. In Kenya, MTCT rates are still estimated at around 14% with over 6,000 newly infected children in 2016.

38 million people are currently living with HIV/AIDS. Although the progress in developing antiretroviral therapies (ART) has been enormous, ART is too expensive or inaccessible for a large fraction of infected individuals, and requires lifelong adherence to a treatment regimen. An HIV cure would address many of these problems, but is still missing.

HIV-infected patients undergoing kidney transplantation are a unique patient subset with significantly increased episodes of graft rejection compared to non-infected transplant recipients. Biomarker development for monitoring of transplant rejection is a critically unmet need, particularly in HIV-infected individuals. Epigenetic mechanisms, including changes in DNA 5-methylcytosine (5mC), contribute to AR and can be used for HIV-infected kidney transplant recipients (HIVKT). screening.

Food insecurity (FI) impacts health via biological, psychological, behavioral, and social-structural pathways. As such, the study of FI in the etiology of poor health has helped illuminate synergistic and multidimensional pathways by which to intervene. For older women of color living with HIV, FI presents a multidimensional challenge and highlights a “Gordian knot” of interactions between aging and living with HIV. For example, HIV accelerates aging-related inflammation that impacts the central nervous system, leading to neurocognitive decline.

Latently infected CD4+ T cells, thought to be the main barrier to HIV cure, are indistinguishable from uninfected cells and are exceedingly rare, rendering the study of HIV latency in vivo particularly challenging. The development of more tractable systems such as in vitro primary cell models of latency has greatly advanced our understanding of the establishment, maintenance and reactivation of HIV latency, since these models permit higher infection frequencies and some employ reporter viruses to readily distinguish latent and productively infected populations.