Vedolizumab (Anti-alpha4beta7) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption

-INCLUSION CRITERIA:

1. Age, 18 - 65 years
2. Documented HIV-1 infection and clinically stable
3. In general good health, with an identified primary health care provider for medical management of HIV infection and willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study
4. CD4+ T cell count >450 cells/mm3 at screening

5. Documentation of continuous cART treatment with suppression of plasma viral level below the limit of detection for more than or equal 2 years. Subjects with blips (i.e., detectable viral levels on cART) prior to screening may be included provided they satisfy the following criteria:

   1. The blips are <400 copies/mL, and
   2. Succeeding viral levels return to levels below the limit of detection on subsequent testing
6. Willingness to undergo ATI

7. Laboratory values within pre-defined limits at screening:

   • Absolute neutrophil count >1,000/mm3
   • Hemoglobin (Hgb) levels >10.0 g/dL for men and >9.0 g/dL for women
   • Platelet count >100,000/mm3
   • Prothrombin time (PT) and partial thromboplastin time (PTT) <1.5 upper limit of normal (ULN)
   • Estimated glomerular filtration rate (eGFR) of greater than or equal to 50 mL/min as determined by the NIH Clinical Center laboratory
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of <1.1 x ULN. Total bilirubin <1.1 x ULN (unless subject is taking atazanavir or has Gilbert s Syndrome)
8. Willingness to have samples stored for future research

Participation of Women:

Contraception: The effects of vedolizumab on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

EXCLUSION CRITERIA:

1. Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
2. Documented nadir CD4+ T cell count <200 cells /mm3
3. Documented multiclass antiretroviral drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study
4. HIV immunotherapy or vaccine(s) received within 1 year prior to screening
5. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment
6. Receipt of other investigational study agent within 28 days of enrollment
7. Any active malignancy that may require systemic chemotherapy or radiation therapy
8. Systemic immunosuppressive medications received within 3 months prior to enrollment. The following are not excluded: [1] corticosteroid nasal spray or inhaler; [2] topical corticosteroids for mild, uncomplicated dermatitis; and [3] oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur (length of therapy less than or equal to 10 days, with completion in more than or equal to 30 days prior to enrollment)

9. History or other clinical evidence of:

   • Significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction)
   • Severe illness, chronic liver disease, malignancy, immunodeficiency other than HIV, active systemic infection other than HIV, or any other condition that, in the opinion of the investigator, would make the subject unsuitable for the study
   • Active or latent tuberculosis, regardless of treatment history
10. Neurologic or neuropsychiatric disorder, the symptoms of which mimic PML and could interfere with the assessment of safety (e.g. history of encephalitis with motor sequela, stroke with sequela, severe major depressive disorder, severe bipolar disorder, seizure disorder)
11. Active drug or alcohol abuse or any other pattern of behavior that, in the opinion of the investigator, would interfere with adherence to study requirements
12. Pregnancy or breast-feeding

Co-enrollment Guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies. Study staff should be notified of co-enrollment as it will require the approval of the Principal Investigator.