A Single Dose of Pembrolizumab in HIV-Infected People

This is an interventional treatment trial for Human Immunodeficiency Virus focused on measuring Immunotherapy, Immunologic Non-Responder, Immunologic Response, Randomized, PD-1 Read More

• INCLUSION CRITERIA:

Individuals must meet all of the following criteria to be eligible for study participation:

Greater than or equal to 18 years of age.

Documented HIV-1 infection (eg, positive standard enzyme-linked immunosorbent assay or rapid HIV-1/HIV-2

antibody test with a confirmatory test such as western blot, or documentation of repeated HIV RNA of > 1000 copies/mL). Outside documentation will be acceptable.

Absolute neutrophil count > 1000/microliter.

Platelet count > 125,000/microliter.

Hemoglobin > 10 g/dL.

Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 1.1 times the upper limit of normal (ULN). Total bilirubin < 1.1 x ULN (unless participant is taking atazanavir or has Gilbert syndrome).

Calculated creatinine clearance (estimated glomerular filtration rate) greater than or equal to 60 mL/min/1.73 m2.

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 will not be excluded if they are on a stable dose of replacement thyroid medication; dose may be adjusted as needed.

No significant underlying pulmonary, cardiac, renal, or hepatic disease, as defined by a need for drug treatment or ongoing physician care.

Under the care of a primary care physician.

Willing to comply with study requirements and procedures including storage of biological specimens for future use in medical research.

Willing to allow genetic testing.

Able to provide informed consent.

Participants of reproductive potential must agree to not become pregnant or to impregnate a partner beginning 30 days before the dose of pembrolizumab through 120 days post dose.

Participants must meet criteria for INR, defined as follows:

1. Has been on a cART regimen for at least 12 months and on a stable regimen for at least 4 weeks.

2. Has HIV suppression, defined as viral load < 40 copies/mL, and documented suppression (below

   detection limits of the utilized assay) for at least 12 months. A viral load of < 500 copies/mL once in the

   year preceding screening will be allowed if there is documentation of a viral load < 40 copies/mL on

   subsequent testing and at screening.

3. CD4+ T-cell count > 100 cells/mm3 and less than or equal to 350 cells/mm3.

EXCLUSION CRITERIA:

Females who are pregnant or breastfeeding.

Has used an investigational drug agent or investigational device within 12 weeks of baseline.

Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Known allergy to any component of the pembrolizumab formulation.

Systemic steroid therapy or other immunosuppressive therapy in the 3 months prior to enrollment. (Inhaled or topical corticosteroids are permitted.)

Has used an immunotherapeutic agent within 6 months of baseline.

Plans to receive any vaccine within 16 weeks of receiving pembrolizumab.

Has active autoimmune disease or a history of autoimmune disease that has required systemic treatment (eg, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, T4) is not considered a form of systemic treatment.

Has known history of, or any evidence of active, non-infectious pneumonitis.

Malignancy requiring systemic therapy, or a history of malignancy that required systemic therapy within the past 5 years. However, cutaneous basal cell carcinoma or cutaneous Kaposi sarcoma not requiring systemic therapy will not be exclusionary.

Has known active hepatitis B (HBV) or potential for HBV reactivation (eg, hepatitis B surface antigen [HBS] reactive, HBV DNA positive, or isolated anti-core antibody positive; individuals who are anti-HBS antibody positive with or without anti-core Ab are eligible).

Has known active hepatitis C (HCV; eg, HCV RNA [qualitative] is detected). Patients who have sustained virologic response (SVR) to anti-HCV treatment are eligible if at least 24 weeks have passed since achieving SVR.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements

of the study.

History or other clinical evidence of:

1. Significant or unstable cardiac disease
2. Significant pulmonary disease
3. Severe illness, chronic liver disease, malignancy, immunodeficiency other than HIV, active systemic infection (other than HIV) requiring therapy.

Opportunistic infection requiring maintenance therapy, including toxoplasmosis, fungal infections other than candida (eg, cryptococcosis, histoplasmosis, coccidioidomycosis), atypical mycobacterial infection. Secondary Pneumocystis, candida, and HSV prophylaxis will be permitted.

Active or history of tuberculosis (TB), or positive TB QuantiFERON Gold test.

Known osteoporosis or diabetes mellitus.

Hemoglobin A1c > 6%.

Fasting triglyceride > 300 mg/dL.

Any condition that, in the opinion of the investigator, would make the participant unsuitable for the study.

Co-enrollment in other trials is restricted, other than enrollment on observational studies or expanded access studies for

antiretroviral agents, during the first 48 weeks of the study.