Early Administration of Romidepsin and 3BNC117 in Treatment-naïve HIV Patients Starting ART

The study will be conducted among ART naïve HIV-1-infected patients.

Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.

Inclusion criteria

• Documented HIV-1 infection
• CD4+ T cell count >200/µL on last visit prior to study entry
• ART naïve
• Able to give informed consent

Exclusion criteria

• Any significant acute medical illness (not including primary HIV infection) in the past 8 weeks
• Any evidence of an active AIDS-defining opportunistic infection
• Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy
• The following laboratory values at screening, but 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) ≤60 mL/min (based on serum creatinine or other appropriate validated markers)
• Platelet count ≤100 x10^9/L
• Absolute neutrophil count ≤1x10^9/L
• Serum potassium, magnesium, phosphorus outside ≥1.5 ULN/LLN
• Total calcium (corrected for serum albumin) or ionized calcium ≥1.5 ULN/LLN
• Hepatitis B or C infection as indicated by the presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood
• ECG at screening that shows QTc >450 ms when calculated using the Fridericia formula from either lead V3 or V4 [86]
• Use of:

• Warfarin or warfarin-derivatives
• HDACi
• An agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening
• Drugs that induce or inhibit CYP3A4 or P-gp
• History of:

• Clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)
• Malignancy or transplantation, including skin cancers or Kaposi sarcoma
• Diabetes mellitus
• 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 romidepsin, 3BNC117 or their analogues
• Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of non-estrogen containing contraceptions (according to the Danish Medicines Agency guidelines) to avoid pregnancy for the 3 week study period and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays
• Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the 3-week study period, and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays