The objective of this study is to determine whether 12 weeks of mesalamine therapy added to a standard HIV treatment decreases systemic immune activation and inflammation in HIV-infected patients, possibly resulting in better recovery of the immune system. The study hypothesis is that decreasing inflammation directly in the gut may decrease both of these potential causes of chronic inflammation, potentially resulting in an immunologic benefit.

While most HIV-infected patients can now achieve nearly complete viral suppression on currently available HIV medications, they still have at least a 10-year shorter life expectancy than the general population and are at higher risk for diseases associated with accelerated aging including cardiovascular disease and non-AIDS-defining cancers. Persistent inflammation and immune activation are believed to drive this increased risk. Despite suppression of viral replication in peripheral blood by effective HIV medications, HIV may continue to be expressed at low levels by T cells in the lining of the gut and may also result in translocation of bacterial products across the lining of the gut, driving persistent inflammation. We believe that decreasing inflammation directly in the gut may decrease both of these potential causes of chronic inflammation, potentially resulting in an immunologic benefit. Mesalamine is an oral anti-inflammatory drug used to treat patients with inflammatory bowel disease, acts locally on the gut tissue to decrease inflammation, and is associated with very few side effects. If mesalamine therapy reduces immune activation and inflammation in our study, it would prompt larger studies to see if mesalamine decreases clinical outcomes like cardiovascular disease, cancer, and mortality in this setting.

Inclusion Criteria:

1. HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry.
2. Stable antiretroviral therapy for at least 6 months.
3. Screening CD4+ T cell count below 350 cells/mm3
4. All available CD4+ T cell counts in the last year and at screening <350 cells/mm3
5. Screening plasma HIV RNA levels below level of detection (< 40 copies RNA/mL).
6. All available plasma HIV RNA levels within past year below the level of detection. Isolated detectable values < 500 c/ml are allowed if HIV RNA levels before and after this time point are undetectable.
7. >90% adherence to therapy within the preceding 30 days, as determined by self-report.
8. Both male and female subjects are eligible. Females of childbearing potential must have negative pregnancy test at screening and agree to use a double-barrier method of contraception during the study.

Exclusion Criteria:

1. Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.
2. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
3. Exposure to any immunomodulatory drug in the past 16 weeks.
4. Active hepatitis C or hepatitis B which will require treatment in the subsequent 24 weeks.
5. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, Hgb < 8mg/dL
6. Pancreatitis or lipase greater than 2 times the upper limit of normal.
7. Renal insufficiency with creatinine clearance less than 50 ml/min
8. Elevated transaminases greater than 2.5 times the upper limit of normal.
9. Evidence of decompensated cirrhosis, heart failure.
10. Pregnant or breastfeeding women

24 weeks