Pilot Award

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.

Antimalarial chemoprevention is an emerging modality to prevent deaths and morbidity from malaria in children living in highly endemic areas, but there are concerns that it will delay the natural acquisition of antimalarial immunity. Recent studies in mice and humans have challenged this paradigm, and suggest that selective blockade of blood stage infection with antimalarial drugs may paradoxically enhance the development of sterilizing antimalarial immunity, but this has not been tested in field settings.

Standard diagnostic strategies for tuberculosis (TB) are inadequate, and result in misuse of resources in public health programs; overutilization of hospital isolation facilities; and anxiety for patients. The reason for this waste is that standard diagnostic tests for TB are either inaccurate (smear microscopy) or slow (mycobacterial culture).

Antimalarial chemoprevention is an emerging modality to prevent deaths and morbidity from malaria in children living in highly endemic areas, but there are concerns that it will delay the natural acquisition of antimalarial immunity. Recent studies in mice and humans have challenged this paradigm, and suggest that selective blockade of blood stage infection with antimalarial drugs may paradoxically enhance the development of sterilizing antimalarial immunity, but this has not been tested in field settings.

Standard diagnostic strategies for tuberculosis (TB) are inadequate, and result in misuse of resources in public health programs; overutilization of hospital isolation facilities; and anxiety for patients. The reason for this waste is that standard diagnostic tests for TB are either inaccurate (smear microscopy) or slow (mycobacterial culture).

The overall objective of this study is to determine if active tuberculosis (TB) case finding among persons residing in the same household as a person with active pulmonary TB (household contact investigation) is an effective TB control intervention in a low-income setting with a high incidence of TB and a high prevalence of HIV infection.

In sub-Saharan Africa, HIV is predominantly transmitted via discordant sexual relationships. With the availability of antiretroviral (ARV) medications, individuals infected with HIV can live relatively normal productive lives. Societal and cultural expectations as well as personal reproductive intentions drive HIV positive women in discordant relationships to conceive. Approximately 50% of HIV infected couples desire children.

The overall objective of this study is to determine if active tuberculosis (TB) case finding among persons residing in the same household as a person with active pulmonary TB (household contact investigation) is an effective TB control intervention in a low-income setting with a high incidence of TB and a high prevalence of HIV infection.

In sub-Saharan Africa, HIV is predominantly transmitted via discordant sexual relationships. With the availability of antiretroviral (ARV) medications, individuals infected with HIV can live relatively normal productive lives. Societal and cultural expectations as well as personal reproductive intentions drive HIV positive women in discordant relationships to conceive. Approximately 50% of HIV infected couples desire children.