Mentored Scientist Award

The proposed study will test the effect of herbal extracts commonly used in Iran by various HIV and cellular based assays available at UCSF, and provide important information to develop effective and affordable anti-HIV latency therapies to those who have limited access to expensive modern medicine. Also, I will maintain the collaboration with Dr. Peterlin after completion of the proposed study during my sabbatical stay at UCSF, which will contribute to potential new discovery of cellular pathways to regulate HIV transcription and latency.

HIV-1 induced B cell dysfunction typically presents as a loss of memory B cells and attenuated antibody responses, paradoxically with concomitant increases in activated B cells and hypergammaglobulinaemia. While some loss of functionality could be due to the loss T cell help, T cell triggering of inhibitory signaling pathways has also been implicated. Of these pathways, members of the TNF-receptor superfamily and subsequent downstream signaling events appear to have a prominent impact on regulating B cell function.

Cardiovascular disease (CVD) is the leading cause of mortality in Latin America and the Caribbean (LAC), and has arisen as a major clinical and public health challenge in HIV. Social and economic vulnerability may potentiate increased CVD risk among PLHIV by reducing access to a healthy diet, increasing stress, and increasing maladaptive coping behaviors (e.g. alcohol consumption and smoking). In particular, research suggests food insecurity as a key structural barrier that may undermine CVD prevention efforts among PLHIV.

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.