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

To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (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.

Eligibility Criteria:
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