| Abstract |
This is a pilot project to study the
changes in the intestinal microenvironment that are associated
with HIV malabsorption and weight loss. Both intestinal malabsorption
and weight loss are prevalent in HIV disease, and have a significant
negative impact on outcome. In vitro studies have shown that
the presence of HIV in intestinal epithelium results in increased
levels of the pro-inflammatory cytokines TNF-alpha, IL1-beta,
and IFN-gamma. Incubation of intestinal epithelial cells with
these cytokines results in changes in both epithelial barrier
and transport function. No study has assessed these changes
clinically in subjects with intestinal malabsorption. In addition,
there have been no studies looking at local viral expression
and viral subtypes in association with intestinal malabsorption.
The proposed study will utilize a nested and matched case-control
study design to identify subjects with and without malabsorption
and weight loss within Nutrition for Healthy Living (NFHL).
NFHL is a large cohort of HIV seropositive subjects that is
being followed for changes in nutritional and dietary parameters
as well as HIV disease progression. Intestinal biopsies will
be obtained from these subjects. Morphometric studies for
inflammatory changes, RT-PCR for relative local mRNA expression
of cytokines, PCR studies for biologic viral phenotype, and
assessment of intestinal HIV viral load will be performed.
Aims: Measure pro-inflammatory cytokines IFN-gamma message,
HIV viral load, and presence of syncytium-inducting (SI) virus
in the intestinal tissues of subjects with and without D-xylose
malabsorption and weight loss.
Methods: Subjects will be selected from within the Nutrition
for Healthy Living Cohort. Twenty subjects with laboratory
defined D-xylose malabsorption and clinically experiencing
unintentional weight loss of over 5% of baseline body weight
will be selected as cases. Twenty controls with neither of
these parameters will be chosen as controls. Controls will
be matched to cases according to broad categories of age (within
10 years), sex, viral load, clinical AIDS status, and use
of anti-retroviral therapy. Intestinal biopsies will be obtained
via upper intestinal endoscopy. These samples will be analyzed
for morphometric inflammatory changes, relative pro-inflammatory
cytokine expression via RT-PCR, intestinal HIV viral load,
and HIV biologic subtype. Intestinal malabsorption will be
characterized by a 72-hour fecal fat collection and a 5 hour
urine collection for mannitol, lactulose, and d-sylose absorption.
Difference will be measured by Student’s two-sample
t-test and Fisher’s exact test.
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