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.

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

Individual deidentified participant data (including data dictionaries) will be shared following the publication of the primary and secondary endpoints as outlined in this protocol. Data to be shared includes deidentified data points in published, peer-reviewed articles. Additional, related documents will also be available (study protocol, informed consent form). Data will become available following publication with no planned end date.

Individual deidentified participant data (including data dictionaries) will be shared following the publication of the primary and secondary endpoints as outlined in this protocol. Data will become available following publication with no planned end date.

Access to the data sharing will be given to researchers who provide a methodologically sound proposal for any type of analysis and requires IRB/Ethics committee approval (if applicable). Proposal should be addressed to olesoega@rm.dk.