Pilot Award

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.

Retention in care is important for the health and well-being of HIV-infected persons. However, we do not know which measures of retention best predict key clinical outcomes such as mortality. In addition, existing studies of retention have only established an association between retention and mortality, rather than a causal effect.

Objectives: 1) accurately measure alcohol and drug use, especially amphetamine-type stimulants (ATS) and HIV prevalence, among female sex workers (FSW) and male clients of FSW in Preah Sihanouk Province, Cambodia, and; 2) assess the synergy between alcohol and/or drug exposures and HIV risks according to the type of sex work venues.

HIV infection can result in a breakdown in intestinal immunity associated with the translocation of immunostimulatory microbial products from the gut lumen to systemic circulation, which initiates and sustains the persistent inflammation that drives progression to AIDS ¹ . In particular, we and others have shown that HIV infection induces a significant loss of IL-17-producing cells, including TH17 cells, that are critical for maintaining the mucosal barrier ^2,3 .

A point-of-care (POC) test that could be implemented at peripheral levels of the health system in low-income countries has been predicted to reduce tuberculosis (TB)-related mortality by one-third. However, no truly POC test is in the diagnostic pipeline. For maximum impact, a POC test should have high specificity such that a positive test result can be followed by the immediate initiation of treatment. However, a highly sensitive but less specific POC test is a more realistic short-term goal and could be used as an important screening tool in peripheral health care settings ?

A point-of-care (POC) test that could be implemented at peripheral levels of the health system in low-income countries has been predicted to reduce tuberculosis (TB)-related mortality by one-third. However, no truly POC test is in the diagnostic pipeline. For maximum impact, a POC test should have high specificity such that a positive test result can be followed by the immediate initiation of treatment. However, a highly sensitive but less specific POC test is a more realistic short-term goal and could be used as an important screening tool in peripheral health care settings ?

Remarkable advances have helped to determine how immune responses act to contain HIV-1 infection, but precise immune correlates of protection still remain largely uncharacterized. The HLA region is a major determinant of genetics linked to viral control. HLA-B*57+ individuals are known to progress slowly to disease, and this allele is overrepresented in elite controllers. My preliminary results show a reduced replicative capacity of HIV-1 in PBMC from seronegative HLA-B*57+ subjects, in comparison to PBMC from subjects carrying HLA-B*35, an allele associated with rapid disease progression.

Remarkable advances have helped to determine how immune responses act to contain HIV-1 infection, but precise immune correlates of protection still remain largely uncharacterized. The HLA region is a major determinant of genetics linked to viral control. HLA-B*57+ individuals are known to progress slowly to disease, and this allele is overrepresented in elite controllers. My preliminary results show a reduced replicative capacity of HIV-1 in PBMC from seronegative HLA-B*57+ subjects, in comparison to PBMC from subjects carrying HLA-B*35, an allele associated with rapid disease progression.

A key challenge of large-scale intervention trials is to adequately describe the social, cultural and operational factors that influence study findings. Qualitative research methods are particularly useful for elucidating the processes through which such trials may affect primary clinical outcomes through social and behavioral change at the community level. This pilot award would launch the qualitative evaluation of a large "test and treat" intervention, the Sustainable East Africa Research in Community Health (SEARCH) trial.