early administration of romidepsin and 3bnc117 in treatment-naïve hiv patients starting art

Conditions: Hiv

Summary: 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

Keywords: hiv-1 latency reversal agent immunotherapy