Mentored Scientist Award

The population of HIV+ individuals achieving viral suppression on combination antiretroviral therapy (cART) is growing, aging, and experiencing a widening spectrum of diseases and conditions that compromise optimal health. Research on aging with HIV is not well characterized and is especially lacking for older HIV+ racial/ethnic and sexual minorities who face particular social and structural barriers to healthy aging. Mobile technology is a tremendously promising tool for integrating access to care and social support that transcends social and structural barriers.

The SUPrEMe Study: Substance Use and PrEP adherence among Men who have sex with men, will examine the prevalence and pattern of substance use over time (Aim 1) and evaluate the association between substance use and PrEP adherence and persistence (Aim 2) among MSM on PrEP in Manila, Philippines. To advance these aims, I will partner with LYS and the WHO Division of Communicable Diseases in the Western Pacific (see letters of support) to conduct a secondary data analysis of the longitudinal data from Project PrEPPY, the first PrEP implementation project in the Philippines.

Rhesus CMV-vectored SIV (RhCMV/SIV) vaccines have been shown to protect half of vaccinated adult macaques against progressive infection. The vectors elicit unconventional Mamu class II- or Mamu E-restricted CD8+ T cells. The viral backbone of RhCMV/SIV vaccines, cytomegalovirus (CMV), is known to have a panoply of immunologic effects including generation of effector-memory CTLs and “memory” NK cells—innate cells with adaptive features.

Pre-exposure prophylaxis (PrEP) has demonstrated effectiveness for daily use to prevent HIV-infection. Despite PrEP being a promising approach for preventing HIV acquisition, the bulk of the empirical literature has focused on men who have sex with men and heterosexual women in sub-Saharan Africa. Women at high-risk of HIV infection in the United States (US) are largely absent from this body of literature.

Tuberculosis (TB) is the leading cause of death among people living with HIV (PLHIV), responsible for over one-third of all HIV deaths worldwide. Eliminating TB in this setting is a necessary step in improving overall morbidity and mortality for PLHIV. The new End TB Strategy put forward by the World Health Organization (WHO) outlines key targets required for achieving global TB control including increasing detection of TB cases in Africa by 50%. However, the process of TB diagnosis can be burdensome on patients due to the potentially catastrophic costs associated with accessing TB care.

Pregnancy-associated malaria, including placental malaria (PM), causes ~100,000 infant deaths per year and maternal HIV infection significantly increases the risk of severe infant morbidity and mortality. Epidemiological studies have reported that children born to mothers with PM have an increased susceptibility to malaria infection. In addition, children born to HIV positive mothers, even those on anti-retroviral therapy (ART), are more prone to severe PM and develop poor vaccine responses.

Untreated HIV infection is distinguished by two major clinical hallmarks: progressive depletion of CD4 T cells, and chronic inflammation. We now know that resting “bystander” CD4 T cells in lymphoid tissue undergo a process of abortive HIV infection where incomplete reverse transcripts are formed and detected by the host DNA sensor, interferon gamma-inducible protein 16 (IFI16). This activation of IFI16 causes the assembly of an inflammasome, which cleaves caspase-1 and causes pyroptosis in the CD4 T cell.

Pre-exposure prophylaxis (PrEP) with once-daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
prevents acquisition of HIV infection [1-4]. Although well tolerated, [5, 6] cases of nephrotoxicity have occurred
during TDF use, especially in HIV-infected individuals. [7-23] Such cases have resolved in most [7, 22, 24-26] but
not all [15, 19, 23, 27] persons after drug discontinuation, and may involve proximal tubular dysfunction [7-13, 16,
17, 19-22, 24, 26, 28], Fanconi syndrome, [16, 24, 25], or glomerular dysfunction.[7, 10, 11, 14, 15, 21-23, 26, 27].

Gastrointestinal (GI) tract tissues harbor a large pool of cells latently infected with HIV. However, their exact identity and the mechanisms of latency are unknown. Transforming growth factor (TGF)-β has several functions in gut homeostasis, including the formation and maintenance of tissue-resident memory (TRM) CD8 T cells. Signaling by TGF-β induces expression of CD103, an αE integrin that binds to epithelial E-cadherin. CD4 TRMs also exist, but only a small proportion express CD103, and the role of TGF-β in their formation, function, and maintenance is unknown.