PD-1 Inhibition to Determine CNS Reservoir of HIV-Infection
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
Intervention: Pembrolizumab
Intervention description: Participants will receive one dose of 2mg/kg of pembrolizumab IV at Week 0.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: HIV; Brain; Immunotherapy

Summary:

      Background:

      HIV affects millions of people. The disease may "hide" in the brain, even in people with
      well-controlled HIV without cancer. Then it may "wake up" and continue. The drug
      pembrolizumab uses the body's immune system to fight cells like cancer cells. It is approved
      to treat some cancers but not HIV. Researchers want to see if it is safe for HIV-positive
      people without cancer. This study is not for HIV treatment; only one dose of the drug will be
      used.

      Objective:

      To learn if the drug pembrolizumab, used to treat certain cancers, is safe for HIV-positive
      people.

      Eligibility:

      Adults ages 18 and older with HIV who are in another NIH protocol

      Design:

      Participants will be screened with:

        -  Medical history

        -  Physical and neurological exams

        -  Blood tests

        -  Lumbar puncture. The lower back will be numbed. A needle will remove fluid from between
           back bones.

        -  FDG-PET/CT. A radioactive sugar will be injected in a thin plastic tube (catheter)
           inserted in an arm vein. Participants will rest for an hour, urinate, then lie in the
           scanner. A mask will hold the head still.

        -  Leukapheresis. An optional procedure at baseline. White blood cells are removed from you
           using a serum cell separator machine

      Women who can become pregnant cannot take pembrolizumab. Men who take it must use 2 kinds of
      contraception.

      Participants will have up to 7 more visits, which repeat some screening tests.

      At 1 visit, participants will get one dose of pembrolizumab by catheter for 30 minutes. They
      will get allergy and pain medicines.

      At 2 visits, participants will have a brain MRI. They will get a contrast agent by catheter.
      They will lie in a metal cylinder that takes pictures for 1-2 hours. They will get earplugs
      for loud sounds.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  18 years or older

          -  Diagnosis of HIV-1 infection, with positive HIV 1 antibody testing

          -  HIV RNA less than or equal to 40 copies/mL in plasma in the last 12 or greater months

          -  CD4 count above 350 cells/uL

          -  Antiretroviral therapy for 12 months prior to trial

          -  Fully vaccinated against SARS-CoV-2. Fully vaccinated is defined as:

               -  Two weeks out from the second dose of a two-dose vaccine series (Moderna,
                  Pfizer-BioNTech); or

               -  Two weeks out from a single-dose vaccine (Johnson & Johnson/Janssen)

          -  Patient must be willing and able to comply with all the aspects of trial design and
             follow-up.

          -  Patients must be able to provide informed consent

          -  Women of childbearing potential must agree to use contraception (defined as two forms
             of effective birth control), from the time of enrollment until 4 months after the last
             exposure to pembrolizumab

          -  Participants who are physically able to father a child must agree to use 2 effective
             methods of contraception (birth control) from the time you enroll in the study until 4
             months after your last exposure to pembrolizumab

               -  Effective methods of contraception for this study include:

                    -  hormonal contraception (birth control pills, birth control patches, injected
                       hormones, hormonal implants or vaginal ring),

                    -  Intrauterine device,

                    -  Barrier methods (condom or diaphragm) combined with spermicide, and

                    -  Surgical sterilization (hysterectomy, tubal ligation, or vasectomy).

                    -  If you have had a hysterectomy, tubal ligation, or vasectomy (or have a
                       partner with a hysterectomy, tubal ligation or vasectomy), you do not have
                       to use 2 methods of birth control.

        EXCLUSION CRITERIA:

          -  Clinically significant medical disorders that might expose the patient to undue risk
             of harm confound study outcomes or prevent the patient from completing the study as
             identified on screening studies and by patient history. Examples of such conditions
             include known cardiac disease such as congestive heart failure, chronic obstructive
             pulmonary disease, uncontrolled hypertension, kidney disease, liver disease, endocrine
             disease, pulmonary disease, heart disease, progressive CNS disease such as Parkinson s
             disease, dementia, prior tuberculosis infection or ongoing CNS opportunistic
             infection.

          -  Patient has received immunomodulatory/immunosuppressive therapy (including IV steroids
             but excluding local injections) in the preceding 6 months.

          -  Patient with known autoimmunity that would include but is not limited to disorders
             such as hypo/hyperthyroidism, myasthenia gravis, diabetes mellitus type 1, hemolytic
             anemia, and immune mediated hepatitis (but excluding patients with hypothyroidism
             already on thyroid replacement therapy).

          -  Prior history of cancer (excluding non-invasive squamous and basal cell carcinoma)

          -  Any opportunistic infection in the prior 2 years (excluding thrush) including latent
             TB (or a positive TB Quantiferon Gold test)

          -  Patient has received other investigational drugs within 3 months before enrollment

          -  Positive serological or PCR evidence of active or prior infection with HTLV-1/II,
             Hepatitis B or C. Patients with hepatitis B core (+), surface antibody (+), surface
             antigen ( ) and hepatitis B DNA (-) eligible to participate in the study (provided
             they are on tenofovir, lamivudine or TAF). Participants with prior hepatitis C who are
             hepatitis C antibody (+) but hepatitis C RNA (-) with normal liver enzymes and no
             evidence of cirrhosis on clinical liver ultrasound are eligible to participate in the
             study.

          -  Metal in the body which would make having an MRI scan unsafe, such as pacemakers,
             stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves,
             cochlear implants or shrapnel fragments, or history of welding or metal worker

          -  Claustrophobia

          -  Inability to lie comfortably on the back for up to two hours.

          -  Abnormal anti-thyroid panel (anti-TPO and anti-TG) test at screening visit.

          -  Abnormal screening/baseline blood tests exceeding any of the limits defined below or
             as deemed exclusionary by the investigators on review:

               -  AST and ALT values >1.1 times ULN

               -  Fasting triglyceride > 300 mg/dL

               -  Total bilirubin >1.1 times ULN (unless participant is taking atazanavir or has
                  Gilbert syndrome)

               -  Creatinine Clearance or eGFR <60 ml/minute (adjusted for race)

               -  Hemoglobin < 10 g/dL

               -  Absolute neutrophil count < 1000/microliter

               -  Platelet count <130,000/mm(3) (if platelet clumping is present on hematology
                  slide review, platelet count <100,000/mm3 is considered exclusionary to study)

               -  Hemoglobin A1c greater than or equal to 6%

               -  Thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) within
                  normal limits. If TSH is not within normal limits then the participant may be
                  eligible if thyroxine (T4) is within normal limits. Participants are not excluded
                  if they are on a stable dose of replacement thyroid medication; dose may be
                  adjusted as needed.

          -  An employee or staff of the NIH