Pilot Award

There is wide agreement that street children carry a greater risk of HIV/AIDS infection than their peers, yet this sub-epidemic has been largely ignored by the HIV research community, in part due to their marginalized status. Our ability to design interventions that will improve the health of street children is compromised by the absence of answers to fundamental questions, including: What are their rates of HIV and STIs? What are the modifiable social and contextual factors that increase their risk for infection? Given their marginalized status, how can they best be reached and recruited?

Publications:

• PubMed# 19211029
• PubMed# 18950160
• PubMed# 19465070
• PubMed# 19265397
• PubMed# 19256497

Natural occurring CD4+CD25+ regulatory T (T-reg) cells have broad immunotherapeutic applications and a greater understanding of the factors influencing their function is important. During untreated early HIV-1 infection there is a progressive and preferential expansion of circulating T-reg cells and such accumulation plays an important role in the inability of the immune system to control viral replication. Despite renewed focus on suppressive T-reg cells, the existence of a reciprocal pathway of immune "contrasuppression" has been suggested by clonal studies in mice.

We propose that during the evolution of primary HIV-1 infection an expansion in the proportion of CD8 T cells expressing the inhibitory receptor, Tim-3, will result in failure to control viral replication. In those who initiate HAART we predict they will experience greater declines in Tim-3 expression. Accordingly, over a one year timeline, the approach will involve the use of sophisticated multiparameteric flow cytometry to assess the phenotype and function of such a CD8 T cell repertoire and assess for statistical significant differences between and within subjects.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the viral etiologic agent of Kaposi's sarcoma (KS). In sub-Saharan Africa, the catastrophic intersection between underlying endemic infection with KSHV and the HIV epidemic has resulted in KS becoming the most common malignancy among adults in many countries and a growing cause of cancer in children.

The dual pandemics of tuberculosis (TB) and human immunodeficiency virus (HIV) have coincided in sub-Saharan Africa. Kenya is a clear example of this situation with high regional HIV prevalence (as high as 17.4%) and highly endemic TB with an annual case rate of 329 per 100,000 people. Children have not been immune from the rise of these pandemics. In Kenya an estimated 200,000 children are HIV-infected and between 10-20% may be co-infected with TB. Children with HIV have 20 times the risk of TB and co-infected children face 3-6 fold increased mortality.

Publications:

• PubMed# 18796674
• PubMed# 19186350
• PubMed# 18688706
• PubMed# 19455012
• PubMed# 19477406