Publications

BACKGROUND

Tuberculosis (TB) is the leading cause of death among people with HIV in sub-Saharan Africa. Expanding access to antiretroviral therapy (ART) may reduce the burden of TB, but to what extent is unknown.

METHODS

In a study of 1044 adults who initiated home-based ART in Tororo, Uganda between 1 May 2003 and 30 June 2005, participants were screened for active TB at baseline and then monitored at weekly home visits. Participants with TB at baseline or follow-up were compared with those without TB to determine factors associated with mortality in those with TB.

RESULTS

At baseline, 75 (7.2%) subjects had TB and a total of 53 (5.5%) were diagnosed with TB over a median of 1.4 years of follow-up (3.90 cases/100 person years). Cumulative mortality was 17.9/100 person-years for those with TB and 3.8/100 person-years for those without TB (P < 0.001). Mortality was associated with low baseline CD4 cell counts [relative hazard (RH), 0.99 per 1 cell/microl increase; P = 0.03] and marginally associated with a body mass index

CONCLUSION

TB remains an important cause of illness and death in patients receiving ART in Uganda. However, both appear to decline markedly, after 6 months of ART.

Adipocytokines are a subset of cytokines produced by adipose tissue and are associated with risk of type II diabetes and atherosclerosis. Levels of adipocytokines differ between Black and White Americans, even after adjustment for differences in adiposity, diseases associated with adipocytokines including type 2 diabetes and cardiovascular disease, and general socioeconomic status indicators such as income. We used a series of ancestry informative markers to estimate genetic ancestry in a population-based study of older Black Americans, and examined the association between genetic ancestry and adipocytokines and soluble receptors to help determine which of these may be most amenable to admixture mapping. We typed 35 ancestry informative markers in 1,241 self-reported Black Americans with available DNA from the Health, Aging, and Body Composition (Health ABC) study with available DNA and used a maximum likelihood approach to estimate percent European ancestry. We used linear regression models to determine the association between these adipocytokines and percent ancestry, and staged models to examine whether adiposity or other measures affected the associations of genetic ancestry and adipocytokines. Mean European ancestry was 22.3+/-15.9%. In multivariate adjusted models, the strongest associations observed were between higher European ancestry and interleukin-6 soluble receptor (IL-6 SR), C-reactive protein (CRP), and adiponectin levels, with interleukin-2 soluble receptor (IL-2 SR) and soluble tumor necrosis factor receptor II (TNF-alpha SR II) also showing more modest but significant associations. The association with adiponectin became stronger after adjustment for adiposity. These novel findings suggest that admixture mapping may identify genetic factors influencing the levels of IL-6 SR, CRP, IL-2 SR, and adiponectin.