Mentored Scientist Award

Persons living with HIV (PLWH) are twice as likely to develop cardiovascular disease (CVD), and this excess risk persists despite viral suppression with antiretroviral therapy (ART). In the past 20 years, the global burden of CVD in PLWH has tripled, accounting for significant disease burden. Dyslipidemia is one mechanism by which HIV infection is associated with atherosclerotic CVD (ASCVD), partly due to side effects of ART.

Persons living with HIV (PLWH) are twice as likely to develop cardiovascular disease (CVD), and this excess risk persists despite viral suppression with antiretroviral therapy (ART). In the past 20 years, the global burden of CVD in PLWH has tripled, accounting for significant disease burden. Dyslipidemia is one mechanism by which HIV infection is associated with atherosclerotic CVD (ASCVD), partly due to side effects of ART.

Inducible T-cell kinase (ITK) belongs to the Tec family of tyrosine kinases, and is expressed in mast cells and T lymphocytes. ITK functions downstream of the T-cell receptor (TCR) and regulates T-cell development, activation and differentiation. The role of ITK signaling in HIV persistence is yet unknown. In this proposal we aim to determine the impact of ITK on?HIV latency reversal and infected cell proliferation in primary CD4+?T cells and cell lines. In addition, we propose to investigate mechanisms regulating establishment of latency by regulating activation status of CD4+T cells.

Inducible T-cell kinase (ITK) belongs to the Tec family of tyrosine kinases, and is expressed in mast cells and T lymphocytes. ITK functions downstream of the T-cell receptor (TCR) and regulates T-cell development, activation and differentiation. The role of ITK signaling in HIV persistence is yet unknown. In this proposal we aim to determine the impact of ITK on?HIV latency reversal and infected cell proliferation in primary CD4+?T cells and cell lines. In addition, we propose to investigate mechanisms regulating establishment of latency by regulating activation status of CD4+T cells.

There is a high prevalence of unhealthy alcohol use (UAU) in sub-Saharan Africa, especially among persons living with HIV (PWH). Persons with UAU are at greater risk of HIV acquisition, while PWH with UAU are more likely to not know their HIV status, not be engaged in care, and experience poor outcomes. UAU also portends to a substantially higher risk of tuberculosis (TB) disease, regardless of HIV status.

There is a high prevalence of unhealthy alcohol use (UAU) in sub-Saharan Africa, especially among persons living with HIV (PWH). Persons with UAU are at greater risk of HIV acquisition, while PWH with UAU are more likely to not know their HIV status, not be engaged in care, and experience poor outcomes. UAU also portends to a substantially higher risk of tuberculosis (TB) disease, regardless of HIV status.

 Young men who have sex with men (YMSM) are disproportionally affected by HIV in the United States, accounting for nearly half of new HIV diagnoses among MSM. Pre-exposure prophylaxis (PrEP) has demonstrated high levels of efficacy for HIV prevention; however, uptake has been suboptimal with uptake barriers including cost; stigma; not wanting to take a daily pill; and difficulty locating providers. New PrEP options are now available for YMSM and have the potential to address many of barriers to PrEP uptake, especially non-daily options which are preferred by many YMSM.

 Young men who have sex with men (YMSM) are disproportionally affected by HIV in the United States, accounting for nearly half of new HIV diagnoses among MSM. Pre-exposure prophylaxis (PrEP) has demonstrated high levels of efficacy for HIV prevention; however, uptake has been suboptimal with uptake barriers including cost; stigma; not wanting to take a daily pill; and difficulty locating providers. New PrEP options are now available for YMSM and have the potential to address many of barriers to PrEP uptake, especially non-daily options which are preferred by many YMSM.

Tuberculosis (TB) remains a major cause of morbidity and mortality for people living with HIV (PWH) worldwide, particularly in low-income settings. HIV and TB are both associated with increased rates of obstructive lung disease (OLD), with post-TB lung disease being an increasingly recognized entity associated with both pulmonary dysfunction and persistent respiratory symptoms. Sex-based differences have been found in TB prevalence, with men demonstrating higher rates of TB in multinational studies. However, whether there are sex-based differences in post-TB OLD among PWH is unknown.

Tuberculosis (TB) remains a major cause of morbidity and mortality for people living with HIV (PWH) worldwide, particularly in low-income settings. HIV and TB are both associated with increased rates of obstructive lung disease (OLD), with post-TB lung disease being an increasingly recognized entity associated with both pulmonary dysfunction and persistent respiratory symptoms. Sex-based differences have been found in TB prevalence, with men demonstrating higher rates of TB in multinational studies. However, whether there are sex-based differences in post-TB OLD among PWH is unknown.