Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV

Inclusion Criteria:

- Documented HIV-1 infection

- Adults age 18-65 years

- On ART for a minimum of 18 months.

- CD4+ T cell count >500 at screening

- HIV-1 RNA plasma level of < 50 copies/mL by standard assays for at least 15 months (a
single viral load measurement > 50 but < 500 copies/mL during this time period is
allowable).

- Able to give informed consent

- Viral reservoir sensitivity to 3BNC117 and 10-1074. (Sensitivity of the viral
reservoir to neutralization by 3BNC117 and 10-1074 will be tested following the
screening visit (i.e. prior to randomization)).

Exclusion Criteria:

- Any significant acute medical illness requiring hospitalization in the past 4 weeks

- Any evidence of an active AIDS-defining opportunistic infection

- Any condition that, in the Investigator's opinion, will prevent adequate compliance
with study therapy

- The following laboratory values at screening, the values can be repeated within the
screening period, but test results must be available before baseline (Day 0) and
checked for eligibility: Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal
(ULN) // Serum total bilirubin ≥3 ULN // Estimated glomerular filtration rate (eGFR)
≤50 mL/min (based on serum creatinine) // Platelet count ≤100 x109/L // Absolute
neutrophil count ≤1x109/L

- Hepatitis B or C infection

- History of: Malignancy, excluding non-melanoma skin cancers, or organ transplantation

- Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days
prior to study entry

- Known resistance to >2 classes of ART

- Known hypersensitivity to the components of lefitolimod, 3BNC117, 10-1074 or their
analogues

- Pre-existing autoimmune or antibody-mediated diseases

- Women who are pregnant or breastfeeding, or unwilling/ unable to use an acceptable
method of contraception (if of child bearing potential)

- Males or females who are unwilling or unable to use barrier contraception during
sexual intercourse until plasma HIV-1 RNA is undetectable using standard assays