Effect of an Anti-Inflammatory Drug on Gut Mucosa in HIV Infected Patients

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00069498

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

The lining of the gastrointestinal tract contains specialized lymphoid tissue that is part of the immune system. Like other parts of the immune system, HIV attacks this lymphoid tissue. This study will evaluate the effect of an anti-inflammatory drug on the lymphoid tissue in the gastrointestinal tracts of people with HIV.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: 5-aminosalicylic acid	Phase 1

Detailed Description

The gastrointestinal tract is the body's largest lymphoid organ. Because it contains significant numbers of activated memory T lymphocytes, it is a prime site for HIV infection and amplification. Mucosal T cells are extremely vulnerable to HIV infection due, in part, to a marked increase in CCR5 co-receptors. Understanding the impact of HIV on the gastrointestinal-associated lymphoid tissue (GALT) is essential and may provide insight into the profound drop in mucosal lymphocytes during early infection, persistence of tissue viral replication in the setting of undetectable plasma viral activity, and compartmentalization of HIV.

Pre-clinical studies have demonstrated that the mucosal compartment in HIV uninfected individuals is characterized by features which enhance vulnerability to HIV infection compared to blood. Once infected, the mucosal response to HIV is inflammation. This study will further evaluate the inflammatory response of mucosal tissue to HIV by examining the effect of the anti-inflammatory drug 5-aminosalicylic acid (5-ASA) on the gut mucosa.

Participants in this study will be randomly assigned to receive either 5-ASA or placebo. Participants will be enrolled in the study for 8 weeks; participants may then elect to continue on 5-ASA for an additional 16 weeks. Participants will have four screening visits in the month prior to beginning the study and four study visits during the 8-week study. Assessments will include medical interviews and physical exams, sigmoidoscopy with mucosal biopsy, and blood tests.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

Impact of Co-Receptor and HIV Viral Burden on Gut Mucosa

Study Start Date :

Oct 1, 1999

Outcome Measures

Primary Outcome Measures

Safety of 4.8 g/day 5-ASA in HIV infected patients with detectable viral load []

Secondary Outcome Measures

Time/trend decrease in mucosal viral RNA load and plasma viral RNA load, compared to placebo []
reduction in cellular infiltration in treated patients versus those taking placebo []
change in inflammation, as measured by tissue destruction []
reduction in soluble inflammation (RANTES), CCR5 expression, and cellular infiltration of CD8 []
changes in certain activation markers in gut []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria

HIV infected
Stable plasma viral load between 500 and 100,000 copies/ml for 3 months prior to study entry
Stable antiretroviral therapy for at least 3 months prior to study entry
CD4 cell count greater than or equal to 200 cells/mm3
Mucosal viral RNA greater than or equal to 100 copies/microg total RNA within 2 weeks of study entry

Exclusion Criteria

Allergy or intolerance to salicylates
Gastrointestinal tract infection causing diarrhea or colonic inflammation
Renal or hepatic disease
Current opportunistic infection
History of extensive small bowel resection (greater than 1/2 the length of the small intestine)
History of intestinal mucosal disease (except HIV)
Chronic, regular use of aspirin and/or anti-inflammatory agents within 7 weeks prior to study entry
Oral, topical, or rectal steroids or 5-ASA within 3 months prior to study entry
Certain laboratory abnormalities
Significant neuropsychiatric symptoms that in the opinion of the study official could impact the conduct or outcome of the study