Evaluating a combination of two HIV treatments for patients with undetectable viral load

A Pilot Open Label Phase I Trial to Evaluate the Safety and the Tolerability of a Combination of Two HIV-1 Inducers in HIV+ Sub-type B Patients Under cART With Undetectable Viral Load

This study is testing a combination of two HIV treatments to see if they can safely help men with undetectable viral loads reduce the virus in their bodies and possibly take breaks from treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 69 Years
• Sex: Male
• Sponsor: ANRS, Emerging Infectious Diseases (Government)
• Drugs / interventions: cART, chemotherapy, radiation
• Locations: 1 site (Bruxelles)
• Trial ID: NCT05230368 on ClinicalTrials.gov

What this trial studies

This pilot phase I trial aims to assess the safety and tolerability of a combination of two HIV inducers in men with subtype B HIV-1 who have maintained an undetectable viral load. The study will involve three cohorts, with treatment and enrollment in subsequent cohorts contingent upon the absence of severe adverse events in previous groups. The goal is to explore new methods for reducing HIV-1 reservoirs, which could potentially allow for treatment-free periods in patients. Participants will receive cycles of Decitabine and Romidepsin as part of the intervention.

Who should consider this trial

Good fit: Ideal candidates are men aged 18-69 with documented subtype B HIV-1 infection who have been on stable antiretroviral therapy for over 36 months and have maintained an undetectable viral load.

Not a fit: Patients with other subtypes of HIV or those who have not maintained an undetectable viral load for the required duration may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to new strategies for managing HIV-1 infection, potentially allowing patients to have treatment-free periods.

How similar studies have performed: While this approach is novel, previous studies have explored similar strategies for targeting HIV reservoirs, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Man aged 18-69 years;
* Man with documented infection with sub-type B HIV-1;
* On cART since more than 36 months before pre- screening and at a stable regimen for at least 2 months before pre-screening and until inclusion;
* HIV plasma viral load persistently \< the threshold (of the local test used) and undetectable during the 12 months prior to pre-screening and until inclusion;
* CD4+ T-cells count nadir ≥ 200 cells per mm3 documented in the medical file; Transient CD4+ T-cells count \< 200 cells per mm3 is allowed for a short period if the value is associated with a single isolated acute infection
* CD4+ T-cells count ≥ 500 cells per mm3 for at least 12 months before pre-screening and until inclusion;
* EBV viral load \< 1000 cp.mL-1, CMV viral load \< 10000 cp mL-1;
* Able and willing to comply with study visits and procedures as per protocol;
* Able to understand, sign and date the written voluntary informed consent form at the pre screening visit prior to any protocol-specific procedures.
* Free, informed and written consent signed by the person and the investigator (at the latest on the day of pre-screening and before any investigation carried out as part of the trial) (law of 7 May 2004. article 6)

Exclusion Criteria:

* Man who want to father a child or refuse contraception (condoms) while receiving treatment and for 3 months following completion of treatment; Man with a female partner of childbearing potential who refuses to use a highly effective contraceptive method during the same period (Experimental treatment period and for 3 months following completion of experimental treatment).
* Clinically significant cardiac disease including QTc-prolongation (QTc value \> 450msec);
* On PI based regimen or regimen containing NNRTI (except Doravirine which is allowed), Ritonavir or Cobicistat;
* Treated with CYP 450 inducer or inhibitor, in particular dexamethasone, carbamazepine, phenytoin, rifabutin, rifapentine and phenobarbital;
* Treated with anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation;
* Treated with warfarin or coumarin derivative;
* History of an AIDS-defining clinical illness (based on CDC classification);
* Active coinfection with viral hepatitis B;
* Active coinfection with viral hepatitis C;
* Received any vaccination within 4 weeks prior to the first administration of the study products and plan to receive throughout the study (with the exception of influenza and COVID-19 vaccines which can be injected 4 weeks after the last administration of the study products as well as the Monkeypox vaccination that will be allowed during trial if participant becomes a contact at risk for monkeypox infection (according to national recommendations));
* Treated with sexual hormone during the administration period of the study treatments (until CXD32);
* Active malignancy that may require chemotherapy or radiation therapy;
* Any significant acute medical illness in the 8 weeks prior to pre-screening and until inclusion;
* Haematological or biochemical laboratory parameters at pre-screening and screening : Hemoglobin (\<LLN), absolute neutrophil count (\<LLN), platelets (\<LLN), INR (\>1.2), Partial Thromboplastin Time (\>ULN); grade ≥ 2 for the following parameters: Total serum Creatinine, urea, uric acid, glycemia, total serum bilirubin, Alkaline Phosphatase (ALP) AST-ALT, gammaglutamyl transferase (GGT), lipasemia, LDH, Ionogram: Na, K, Ca, Mg, CRP, albumin, proteins, CPK;
* Liver insufficiency (Child Pugh score \>5);
* Kidney insufficiency (Estimation of glomerular filtration\<60mL/mn/1,73m2 ; evaluation with CKDepi formula, according to the 2012 French Haute autorité de santé recommandations);
* Participant under guardianship or curatorship or deprived of their liberty by a judicial or administrative decision
* Participant potentially inable to follow the protocol requirements (e.g. comprehension of the study requirements, ability to understand and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits).
* Participating to another interventional study or still in an exclusion period from another clinical trial ;
* Planning to participate in a study within 3 months after the end of the present trial.

Where this trial is running

Bruxelles

• CHU Saint-Pierre — Bruxelles, Belgium (Recruiting)

Study contacts

• Study coordinator: Manon Ollivier, PharmD

Conditions HIV-1-infection, Subtype b