Mentored Scientist Award

Tuberculosis (TB) remains the leading cause of death among people with HIV (PWH) globally and even among those with high CD4 counts during ART-mediated viral suppression. Evidence from animal studies indicate that interleukin (IL)-17 producing T cells (TH17) are likely beneficial in host immune response to Mycobacterium tuberculosis infection. TH17 cells are also important in HIV infection as loss of TH17 cells likely contributes to progression to AIDS through breakdown in mucosal immunity.

Dolutegravir was recently recommended as a component of first-line antiretroviral therapy (ART) for all adults living with HIV by the World Health Organization due to improved efficacy and tolerability over prior regimens. However, recent studies, including two randomized trials in sub-Saharan Africa, have shown significant weight gain associated with dolutegravir among ART-naïve patients newly initiating dolutegravir. It is not known whether switch to dolutegravir among ART-experienced patients will result in similar weight gain.

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.