Pilot Award

The Women's Interagency HIV Study (WIHS) is a longitudinal cohort study of women with HIV, and a risk-set match control group; the women enrolled are primarily African American and Latina, with a small number of Asian and Caucasian non-Hispanic women. In Fall of 2011, the WIHS National Community Advisory Board (NCAB) requested to receive their individual estimates of ancestry admixture that are being used as covariates in genomic studies.

The increasing call for community-level evaluation of "combination HIV prevention" (packages of our best evidence-based HIV prevention interventions) has brought to the forefront the need to develop novel methods of both evaluating these combinations of interventions in aggregate and estimating the relative contributions of individual components of the combined intervention. However, such comprehensive methods do not exist.

The Women's Interagency HIV Study (WIHS) is a longitudinal cohort study of women with HIV, and a risk-set match control group; the women enrolled are primarily African American and Latina, with a small number of Asian and Caucasian non-Hispanic women. In Fall of 2011, the WIHS National Community Advisory Board (NCAB) requested to receive their individual estimates of ancestry admixture that are being used as covariates in genomic studies.

The increasing call for community-level evaluation of "combination HIV prevention" (packages of our best evidence-based HIV prevention interventions) has brought to the forefront the need to develop novel methods of both evaluating these combinations of interventions in aggregate and estimating the relative contributions of individual components of the combined intervention. However, such comprehensive methods do not exist.

Chronic immune activation is a significant determinant of HIV-mediated CD4+ T cell loss and disease progression. Despite effective viral suppression, chronic inflammation persists at levels higher than in uninfected people, yet the inflammatory stimuli and the mechanisms by which inflammation persists and promotes disease pathology are not completely understood. Many mechanisms likely contribute to chronic immune activation including persistent antigenemia, depletion of T regulatory cells (Tregs), and stimulation of toll-like receptors.

My research has consistently focused on the effects of poverty and of social/cultural context on the health of our most disadvantaged youth, particularly homeless youth in San Francisco and street children in Kisumu, Kenya. Through my work in San Francisco since 2001, I demonstrated the feasibility of longitudinal epidemiological work with street youth, demonstrated the role of street culture, social networks and race in HIV risk of street youth, and developed a community collaborative project for street-based STI testing of street youth.

Chronic immune activation is a significant determinant of HIV-mediated CD4+ T cell loss and disease progression. Despite effective viral suppression, chronic inflammation persists at levels higher than in uninfected people, yet the inflammatory stimuli and the mechanisms by which inflammation persists and promotes disease pathology are not completely understood. Many mechanisms likely contribute to chronic immune activation including persistent antigenemia, depletion of T regulatory cells (Tregs), and stimulation of toll-like receptors.

My research has consistently focused on the effects of poverty and of social/cultural context on the health of our most disadvantaged youth, particularly homeless youth in San Francisco and street children in Kisumu, Kenya. Through my work in San Francisco since 2001, I demonstrated the feasibility of longitudinal epidemiological work with street youth, demonstrated the role of street culture, social networks and race in HIV risk of street youth, and developed a community collaborative project for street-based STI testing of street youth.

CD4+ T cell depletion is a hallmark of HIV infection and the CD4+ T cell count is useful for staging patients as they progress to AIDS. However, a bulk lymphocyte count does not take into account the diversity of recognition specificities these T cells have. Using a novel quantitative assay of T cell receptor (TCR) genetic diversity, called AmpliCot, we have found that untreated HIV infection is associated with an order of magnitude decrease in blood T cell diversity and that these decreases correlate with CD4+ counts.

One reason HIV-1-infected subjects fail to control viremia is due to the high rate of mutation of HIV-1, with consequent escape from the immune response, especially from neutralizing antibodies. Approximately 8% of the human genome is composed of human endogenous retroviruses (HERVs). Most HERVs are fixed in the human genome, defective in replication, and transcriptionally silent in normal cells. Previous studies have shown members of the HERV-K (HK) family are reactivated during HIV-1 infection.