The DC D-CFAR would like to congratulate the awards recipients for the spring cycle of the 2014 DC D-CFAR Pilot Awards Program.
The DC D-CFAR Pilot Awards Program is a competitive research award that provides pilot funds to HIV/AIDS investigators to assist them in the development of their NIH-funded research careers. This program is designed to encourage new and novel work by early stage investigators, underrepresented racial and ethnic minority groups and women, established investigators in other fields who wish to transition into HIV/AIDS research and investigators proposing translational or collaborative research projects. To date, the DC D-CFAR has funded 27 awards for a total of $1.1 million.
The fall 2014 DC D-CFAR Pilot Awards cycle will be announced shortly. Pre-submission forms will be due on September 26th, and full applications will be due December 5th.
Please join us in congratulating our award recipients in their HIV research achievements.
Sebel Kassaye, MD, MS
"HIV Transmission Dynamics and Drug Resistance in Washington, DC"
Public health efforts to prevent HIV transmission are tailored to the local epidemic, with specific interventions geared to specific risk groups. HIV reporting captures reported risk factors for HIV, but the risk for HIV is heavily influenced not only by individuals' behavior, but also by social and sexual contacts. Risk of transmission is not uniform - for example, 'high risk' sexual activity may not result in HIV transmission if all involved parties are HIV-negative and are not in the 'window period' during which identification of HIV infection requires special testing. However, high risk behavior within a group with a high proportion of HIV-positive individuals is more likely to result in a transmission event.
Dr. Kassaye and colleagues proposed that characterizing HIV transmission networks to identify large HIV transmission clusters by studying the virus will increase understanding of the local HIV epidemic and could potentially guide HIV prevention strategies. This project aims to study the patterns of HIV transmission and transmitted drug resistance in Washington, DC. Identification of large HIV clusters can inform public health efforts for targeted interventions to interrupt ongoing HIV transmission using new HIV treatment and prevention methods including treatment as prevention of HIV-positive individuals and use of pre-exposure prophylaxix (PrEP) among HIV-negative individuals.
Andre Rui Raposo, PhD
"Intrinsic Resistance Factors and the Latent HIV-1 Reservoir"
HLA-B*57 stands out as a major allele associated with lower viral loads in Caucasians. However, this host genetic trait only account for about 25% of the variance in HIV-1 viral load. It is also not well understood why some HLA-B*57 individuals progress at a more rapid rate compared to others who have the allele but are slow progressors. This suggests that additional anti-HIV-1 factors are at play in the control of viremia in individuals carrying protective HLA-B alleles.
Recently, a number of intrinsic immune factors have been identified which are expressed in HIV-1 target cells and restrict retroviral infection in vitro. Emerging data suggest that these factors may be attractive targets for curative approaches. Given these findings we hypothesize that HLA-B*57 HIV-1-infected individuals possess a better control of HIV-1 replication caused by the pre-existing overexpression of host restriction factors. This pre-mobilized defense against retroviral infection in HLA-B*57 individuals may be at the basis for the inefficient establishment of the latent viral reservoir.
Dr. Raposo and colleagues proposed a series of experiments to determine the relevance of host restriction factors in HIV-1 latency and reservoir size. This basic science to translational study should yield valuable insights into the relevance of intrinsic immune mechanisms to the eradication of HIV-1 and the investigators aim to develop an approach to boost the host's natural pre-mobilized defense against HIV-1, and potentially to convert HIV-1-infected individuals into elite controllers.
Marc Siegel, MD
"The Impact of HCV on Aging Through Immune Activation in HIV Infected Subjects"
The purpose of this pilot study is to obtain preliminary data from different groups of subjects in order to examine the influence of HCV infection on serum and cellular markers of immune activation in HCV/HIV co-infected patients. These results will be correlated with aging by assessing telomere length as a biomarker for biological aging in vivo.
Dr. Siegel and colleagues hypothesize that co-infection with HCV accelerates the rate of aging in HIV infected subjects by exaggerating the level of immune activation. The study will consist of 4 groups of age-matched subjects. Group 1 will include 15 HCV/HIV uninfected subjects who will be our control group. Group 2 will include 15 HIV infected subjects who are suppressed on antiretroviral therapy, Group 3 will include 15 noncirrhotic subjects with untreated chronic hepatitis C, and Group 4 will include 15 noncirrhotic HCV/HIV co-infected subjects who are suppressed on antiretroviral therapy but naïve to HCV therapy.
All of the subjects in each group will have serum inflammatory cytokines associated with the immune activation analyzed including sCD14, sCD163, IL-6, D-dimer, TNF-α, hsCRP, and IP-10. In addition, cellular markers of immune activation will be investigated by measuring the proportion of CD4+ and CD8+ T cells coexpressing HLA-DR, CD69 and CD38.
Finally, premature aging will be assessed by measuring telomere length and these results will be correlated to the levels of immune activation that was identified. The elevated markers of immune activation that are identified as being correlated with accelerated aging from this preliminary study will be looked at in a more extensive prospective study. The investigators plan on examining the effects of either statin therapy or HIV integrase therapy, both of which have been shown to decrease markers of immune activation, on the levels of these cytokines.