Combining Latency Reversing Agents to Address the HIV Reservoir

Starting soon · Phase 1/Phase 2

Conditions studied: HIV (Human Immunodeficiency Virus), HIV -1 Infection

In brief

The PLUTO trial aims to contribute to the worldwide search for a functional cure of HIV. One the strategies ("shock and kill' strategy) aims to reverse the HIV-reservoir from latency by increasing cell-associated HIV-RNA, which will lead to increased antigen presentation, trigger immune recognition, and facilitate the elimination of reservoir cells. Participants of the trial are adults with HIV with undetectable viral load that are able to give informed consent to participate in the trial, in total 30 patients will be recruited. The investigational medical compounds in this trial are topiramate, lenalidomide and pyrimethamine, which will be combined. These are all licensed drugs for other conditions. The study consists of two phases. In phase I participants will receive a single dose of the IMPs, as combination therapy. Sampling will be performed before, during and after medical treatment to evaluate latency reversal and safety endpoints. In phase II, participants will receive the combination of IMPs which is the most potent and within safety limits selected from phase I during a four-week treatment. Sampling will take place on a weekly basis to assess latency reversal, reservoir reduction and safety. Participants will be recruited from the Erasmus MC, Amsterdam university Medical Center, Radboud University Medical Center and the University Medical Center Utrecht.

Key facts

Study ID: NCT07384624
Run by: Erasmus Medical Center
People needed: 30
Starts: 2026-04-01
Expected to finish: 2028-07-01
Last updated by the study team: 2026-02-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Documented HIV-1 infection, confirmed by 4th generation ELISA, Western Blot or PCR.
Age ≥ 18 years old.
Confirmed HIV1, subtype A, B, C or D.
Uninterrupted ART therapy for a minimum 6 months. .
Plasma HIV RNA <≤50 copies/ml prior to inclusion at two consecutive measurements at least three months apart.
No disclosed missed ART on more than 2 days per month.
Current blood CD4+T-cell count of ≥200 cells/mm3
No clinical signs of cellular immunodeficiency or AIDS.
Pre-ART plasma HIV RNA ≥1000 copies/mL.
Able to understand provided information and to give informed consent.

You may not qualify if…

Prior exposure to any of the studied LRAs in the previous 90 days
HIV-2 (double)infection
Co-infection with hepatitis B, unless resolved HBV (anti-HBc positive, anti-HBs positive and HBsAg negative) OR HBsAg positive and on continuous HBV-active antiviral therapy for ≥24 weeks prior to dosing, and HBV DNA undetectable or ≤ 200 IU/mL on two measurements (screening and within 4 weeks prior to enrolment), and no history of advanced fibrosis/cirrhosis (stage F2 and higher)
Co-infection with hepatitis C, measured by the presence of hepatitis C virus RNA in blood.
Co-medication with clinically significant interactions with LRA
mRNA vaccine or adjuvant vaccine (e.g. Shingrix) in the previous 8 weeks.
Megaloblastic anaemia due to folate deficiency and untreated haemolysis of any cause
Active malignancy during the past year with the exception of basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi's sarcoma treated with ART alone or other indolent malignancies.
History of suicide attempt or suicidal ideation.
History of ophthalmological medical problems leading to glaucoma or visual field disturbances (e.g. macula oedema). Refraction abnormalities that can be corrected by lenses are acceptable.
History of any medical condition with a causal relationship with hyperammonemia.
History of epileptic seizures in the previous year.
Registered allergies for any of the investigational medical products
Sexually active participants who do not fit any of the following:
a) Female subject of childbearing potential willing to comply with pregnancy tests before start and four weeks after end of treatment and willing to use of double contraceptive measures during and until 1 week after administration of study medication. Non-childbearing is defined by one of the following criteria: amenorrhoea for ≥ 1 year, premature ovarian failure, assigned male at birth, or having undergone bilateral salpingo-oophorectomy, or hysterectomy. b) Sexually active male PLWH who have sex with female partners of childbearing potential and willing to abstain from sex or willing to use condom protection during and until 1 week after administration of study medication.
c) Sexually active male PLWH who have sex with postmenopausal female partners and willing to abstain from sex or willing to use condom protection or with a postmenopausal female partner on pre-exposure prophylaxis during and until 1 week after administration of study medication.
d) Male PLWH who have sex with male partners and willing to abstain from sex or willing to use a condom protection during and until 1 week after administration of study medication.
e) Male PLWH who have sex with male partners on preexposure prophylaxis during and until 1 week after administration of study medication.
Any lab abnormalities at screening as listed below:
Moderate kidney impairment, defined as eGFR <50 mL/min. In PLWH on dolutegravir- or bictegravir-based ART regimens, cystatin C-based eGFR can be used, since possible drug interference with tubular creatinine excretion which leads to eGFR underestimation.
Moderate hepatic impairment, defined as bilirubin > 3 x upper limit of normal (ULN) or ALT > 3x ULN
Inadequate blood counts, defined as: haemoglobin <6.5 mmol/L (males) or <6.0 mmol/L (females), Absolute neutrophil count <1000 cells/mm3, thrombocytes <100 x109/L, international standardized ratio >1.6, activated partial thromboplastin time >40 seconds,

Where it is running

Amsterdam University Medical Center — Amsterdam, Netherlands
Radboud University Medical Center — Nijmegen, Netherlands
Erasmus MC — Rotterdam, Netherlands
University Medical Center Utrecht — Utrecht, Netherlands

Full record on ClinicalTrials.gov

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