Grant Details
Grant Number: |
3R01CA054053-10S1 Interpret this number |
Primary Investigator: |
Palefsky, Joel |
Organization: |
Univ Of California At San Francisco |
Project Title: |
Natural History of Anal Neoplasia in HIV Infected Men |
Fiscal Year: |
2002 |
Abstract
DESCRIPTION (adapted from the Abstract): This is a re-submission of a
competing renewal application for continuing support of a grant entitled
"Natural History of Anal Neoplasia in HIV-infected Men" (R01 CA54053). Data
from the first five years of the study show a high baseline prevalence of
anal disease among HIV-positive men and a very high incidence of anal
squamous intra-epithelial lesions (ASIL), including high-grade squamous
intra-epithelial lesions (HSIL). With the recent advent of "highly active
and retroviral therapy" (HAART), which includes protease inhibitors,
possibly HIV-positive individuals will live longer, and may show a shift in
the HIV epidemic from morbidity and mortality from opportunistic infections
to those of more chronic diseases with a slow natural history, such as
cancer. Because anal HSIL likely represents the precursor lesion to
invasive anal cancer, and progression to cancer may take a number of years,
the increased longevity of HIV-positive individuals due to HAART may,
therefore, increase their risk of anal cancer. This is especially of
concern given the preliminary data which suggest that the improved immune
function associated with HAART does not lead to anal disease regression
among men with ASIL before they began HAART. Thus, with the use of HAART a
substantial number of HIV-positive men may be at risk of invasive anal
cancer. In this renewal, the Investigator has three specific aims: (1) to
study the natural history of ASIL and anal human papilloma virus (HPV)
infection among patients on HAART; (2) to compare the natural history of
ASIL and anal HPV infection to those not on HAART; and (3) to continue
follow-up of the HIV- patients to define more fully the natural history of
ASIL and anal HPV infection in these men. To reconstitute their cohort,
this research group will recruit 350 new HIV-positive patients without HSIL
and will continue to follow their existing HIV-positive and HIV-negative
patients. The researchers will examine the men at 6-month intervals with an
interview, an anal examination including cytology, HPV testing, and anoscopy
with biopsy of visible disease. Blood will be obtained from HIV-positive
patients for CD4/CD8 counts and HIV viral load at each visit. In all
patients, additional anal examinations will be performed at 3-month
intervals if anal disease is detected on cytology or histology. All
patients diagnosed with HSIL will be referred for therapy. Similar to
cervical cancer but unlike other malignancies related to HIV, invasive anal
cancer is most likely a preventable disease. Because a large proportion of
HIV-positive individuals will soon be on HAART, an understanding of the
effect of these drugs on the natural history of anal disease and anal HPV
infection will be essential in order to design a screening program for high
risk individuals as well as better treatment and prevention efforts.
Publications
None. See parent grant details.