Mentored Scientist Award

Trans women bear a disproportionate burden of HIV worldwide. Within this population, Black trans women face a disparity within this disparity, with higher prevalence of HIV and worse clinical outcomes. The extraordinarily high burden of HIV among Black trans women merits urgent investigation. This study proposes to investigate racial/ethnic disparities in the population most severely affected by HIV worldwide – Black trans women, with inclusion of African-Americans and Afro-Brazilians as part of the wider African diaspora.

Levels of cerebrospinal fluid (CSF) HIV antibodies are theorized as a broad marker of central nervous system (CNS) HIV reservoir size. In the proposed work, I will determine CSF HIV antibody levels and their antigenic targets in virally suppressed HIV+ elders with (n=30) and without (n=15) HIV-associated neurocognitive disorder (HAND).

The current limitations of antiretroviral therapy is driving interest in alternative therapeutics which fully resolve inflammation and achieve complete eradication of HIV latently-infected cells. Exosomes are nano-sized membrane vesicles and key players of intercellular signaling. Interestingly, exosomes have shown promise as engineerable therapeutic agents for a broad range of diseases. The objective of this grant is to surface engineer exosomes ex vivo using surface display technology and pack the decorated exosomes with cytotoxic cargo.

Evidence is mounting that gender-based violence (GBV) is a major barrier to engagement in HIV care and treatment, and viral suppression. Research has documented the powerful role of GBV on ART uptake and adherence, including a meta-analysis showing that intimate partner violence had a larger effect on adherence than other factors such as stigma, financial constraints, and pill burden. Yet four key gaps in knowledge remain.

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.