Sitagliptin for Reducing Inflammation and Immune Activation
Condition: HIV-1 Infection
MeSH terms: Inflammation
Intervention: Sitagliptin; Placebo for sitagliptin
Intervention description: 100 mg one tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up; One tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up.
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Sitagliptin; Inflammation; Immune activation; Viral suppression; HIV-1; Immunology biomarkers; sCD14

Summary:

      The purpose of the study is to evaluate whether sitagliptin (Januvia is the brand name for
      sitagliptin) reduces inflammation and immune activation markers in HIV-infected men and women
      when compared to a placebo (inactive medication like a dummy pill). The study evaluated
      whether taking 100 mg of sitagliptin by mouth daily for 16 weeks is safe and effective for
      HIV-infected persons on antiretroviral therapy (ART) who do not have diabetes. Sitagliptin is
      a medication that is used to treat people with diabetes (high blood sugar) but also may
      reduce inflammation in the body.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented HIV-1 infection.

          -  Currently on an antiretroviral regimen consisting of at least 2 NRTIs and either a
             protease inhibitor boosted with low dose ritonavir, an integrase inhibitor, or an
             NNRTI. (Other ART regimens may be acceptable. Sites must consult the protocol team for
             approval)

          -  Currently on continuous ART for ≥48 weeks prior to study entry with no interruption
             longer than 7 consecutive days during that period.

          -  Plasma HIV-1 RNA levels below 75 copies/mL for at least 48 weeks prior to study entry.
             The participant must have a minimum of two values in the last 48 weeks obtained >30
             days apart, with the most recent value obtained within 90 days prior to entry. (Single
             determinations that are between the assay quantification limit and 500 copies/mL
             (i.e., "blips") are allowed as long as the preceding and subsequent determinations are
             below the level of quantification).

          -  CD4+ cell count ≥100 cells/mm^3 obtained within 90 days prior to study entry.

          -  The following laboratory values obtained within 90 days prior to entry.

               -  Absolute neutrophil count (ANC) ≥750/mm^3

               -  Hemoglobin ≥8.0 g/dL

               -  Platelet count ≥50,000/mm^3

               -  Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the
                  Cockroft-Gault formula NOTE: Calculation for the Cockcroft-Gault equation is
                  available at https://www.fstrf.org/apps/cfmx/apps/common/Portal/index.cfm

               -  Aspartate aminotransferase (AST) (SGOT) ≤5 x upper limit of normal (ULN).

               -  alanine aminotransferase (ALT) (SGPT) ≤5 x ULN.

               -  alkaline phosphatase ≤5 x ULN.

               -  Total bilirubin ≤2.5 x ULN (if the participant is receiving atazanavir, a total
                  bilirubin of ≤5 x ULN is acceptable).

               -  Hemoglobin A1C ≤6.5%

          -  For females of reproductive potential, adequate contraception.

          -  Karnofsky performance score ≥70 within 90 days prior to entry.

          -  Ability and willingness of participant or legal guardian/representative to provide
             informed consent.

          -  Participants on statin therapy must be stable on the same dose for at least the prior
             12 weeks with no anticipated change in statin or dose during the intervention.

        Exclusion Criteria:

          -  Change in the ART regimen within the 12 weeks prior to study entry, or
             anticipated/intended modification of ART during the study period.

          -  Two or more HIV-1 RNA determinations >200 copies/mL within the 48 week period prior to
             study entry.

          -  History of clinical pancreatitis or diabetes mellitus diagnosed by a medical provider.

          -  Acute or chronic liver disease with evidence of cirrhosis or portal hypertension.

          -  Chronic hepatitis C (defined as HCV antibody positive and HCV RNA detectable).

          -  History of chronic hepatitis B (defined as surface antibody negative, surface antigen
             positive, and/or HBV DNA detectable).

          -  Use of any immunomodulator, HIV vaccine, investigational therapy, or anti-TNF
             therapies within 90 days prior to study entry.

          -  Active malignancy with expected need for systemic chemotherapy or radiation therapy
             during the study period.

          -  Use of human growth hormone, tesamorelin, testosterone or anabolic steroids within 90
             days prior to study entry (except chronic, stable, replacement dosages in men with
             diagnosed hypogonadism is allowed).

          -  Pregnant or breastfeeding.

          -  Use of any anti-diabetic medication or GLP-1 analogues within the 12 weeks prior to
             study entry.

          -  Current diagnosis of congestive heart failure.

          -  Known allergy/sensitivity or any hypersensitivity to components of the study drug or
             its formulation.

          -  Active drug or alcohol use or dependence that, in the opinion of the site
             investigator, would interfere with adherence to study requirements.

          -  Acute or serious illness requiring systemic treatment and/or hospitalization within 90
             days prior to entry.