Safety and Immunotherapeutic Activity of an Anti-PD-1 Antibody (Cemiplimab) in HIV-1-infected Participants on Suppressive cART

This study will evaluate the safety and immunotherapeutic activity of an anti-PD-1 antibody
(cemiplimab) in HIV-1-infected participants on combination antiretroviral therapy (cART) who
have HIV-1 RNA below the limit of quantification and CD4+ T cell counts greater than or equal
to 350/mm^3.

Participants will be enrolled into three sequential dose-rising cohorts. Participants in each
cohort will receive infusions of either cemiplimab or placebo at study entry (Day 0) and Week
6, for a total of two infusions. All participants will also continue their non-study provided
ART regimen. Enrollment in the cohorts will be sequential, with the second and third cohorts
receiving the first infusion after all participants in the previous cohort have reached week
12 and an evaluation of safety outcomes is completed.

Participants will attend study visits on Day 0 and Weeks 1, 2, 4, 6, 7, 8, 10, 12, 16, 20,
24, 28, 36, and 48. These visits may include a medical history, physical examination, urine
and blood collection, and adherence assessments. Participants will be followed for 48 weeks.

Inclusion Criteria:

- HIV-1 infection

- On ART for at least 24 months

- Receiving ART with no changes of the components of ART medications within 90 days
prior to study entry

- Changes within drug class, in drug formulation or dose are allowed more than 30
days prior to study entry.

- CD4+ T cell count greater than or equal to 350 cells/mm^3

- At least two plasma HIV-1 RNA below quantifiable limit within 18 months

- A single detectable HIV-1 RNA but less than 1000 copies/mL is allowed if followed
by HIV-1 RNA below quantifiable limits.

- HIV-1 RNA level less than the quantification limit within 90 days prior to study entry

- The following laboratory values within 90 days prior to entry:

- Absolute neutrophil count (ANC) greater than or equal to 1500 cells/mm^3

- Hemoglobin greater than or equal to 14.0 g/dL for men and greater than or equal
to 12.0 g/dL for women

- Platelet count greater than or equal to 150,000/mm^3

- Creatinine clearance greater than or equal to 60 mL/min

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
limits

- Normal thyroid, adrenal and diabetes testing

- Negative tuberculosis (TB) test result, OR documentation of completed TB prophylaxis
treatment

- HCV antibody negative result or, if HCV antibody positive, undetectable HCV RNA result

- Negative HBsAg result

- 18 - 64 years of age

- Ability and willingness to provide informed consent.

- Ability and willingness to continue cART throughout the study.

- Female participants must have a negative pregnancy test. Agree not to participate in a
conception process (e.g., active attempt to become pregnant or to impregnate, sperm
donation, in vitro fertilization, egg donation) during the study.

- When participating in sexual activity that could lead to pregnancy, agree to use at
least two reliable forms of contraception simultaneously during the study through week
48.

- Participants who are not of reproductive potential (women who have been
post-menopausal for at least 24 consecutive months or have undergone hysterectomy
and/or bilateral oophorectomy or salpingectomy or men who have documented azoospermia
or undergone vasectomy) are eligible without requiring the use of contraceptives.

- Weight greater than or equal to 50 kg (110 pounds)

Exclusion Criteria:

- History of malignancy within the last 5 years.

- Prior non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin
cancer) is not exclusionary with documentation of complete resection at least 3
months prior to enrollment.

- HIV-related opportunistic infections within the last 5 years

- Chronic obstructive pulmonary disease (COPD).

- Prior radiation therapy.

- Active or previously treated active TB.

- Active asthma requiring any treatment in the prior 2 years, Type I or type II diabetes
mellitus.

- History of or active autoimmune disorders including but not limited to inflammatory
bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis,
systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis,
adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis,
hypophysitis, or sarcoidosis.

- Immune deficiency other than that caused by HIV infection.

- Currently breastfeeding or pregnant.

- Known allergy/sensitivity or any hypersensitivity to mAb-based biologics, cemiplimab
(anti-PD-1) 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.

- Received investigational drug or device within 6 months prior to study entry.

- Use of or intent to use immunomodulators (e.g., interleukins, interferons,
cyclosporine, systemic corticosteroids exceeding physiologic doses), HIV vaccine, or
systemic cytotoxic chemotherapy within 60 days prior to study entry.

- NOTE: Participants receiving stable physiologic glucocorticoid doses, defined as
prednisone less than or equal to 10 mg/day or the equivalent, will not be
excluded. Stable physiologic glucocorticoid doses should not be discontinued for
the duration of the study. In addition, participants receiving topical
corticosteroids will not be excluded.

- Any vaccination within 30 days

- HCV treatment within 6 months

- Prior immunoglobulin (IgG) therapy.

- Current use or intent to use biotin greater than or equal to 5 mg/day, including
within dietary supplements.

- A history of chronic congestive heart failure or other significant cardiac conditions.

- Any active clinically significant medical condition that, in the opinion of the site
investigator, would place the participant at increased risk.