HIV (Human Immunodeficiency Virus)Phase 1/2PLUTONCT07384624
Combining Latency Reversing Agents to Address the HIV Reservoir
A Phase 1/2 study testing Pyrimethamine (PYR), Lenalidomide and Topiramate (drug) in people with HIV (Human Immunodeficiency Virus) and HIV -1 Infection, run by Erasmus Medical Center at 4 sites in Netherlands.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV (Human Immunodeficiency Virus), HIV -1 Infection
- What is being tested?
- Pyrimethamine (PYR), Lenalidomide and Topiramate (drug)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesNetherlands
- Study dates
- Apr 2026to Jul 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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:
- 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.
- 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.
- 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.
- 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,
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Daniek Teijema, MD contact
Netherlands4 sites
Amsterdam University Medical Center
Amsterdam
Michelle Klouwens, MD, PhD
Michelle Klouwens, MD PhD
Radboud University Medical Center
Nijmegen
Rob Arts, MD, PhD
Rob Arts, MD PhD
Erasmus MC
Rotterdam
Casper Rokx, MD PhD, +31681336328, c.rokx@erasmusmc.nl
Daniek Teijema, MD, d.teijema@erasmusmc.nl
University Medical Center Utrecht
Utrecht
Annelies Verbon, MD PHD, a.verbon@umcutrecht.nl
Annelies Verbon, MD PhD
About this study
Official title: Curing HIV: Proof of Concept Randomized Clinical Trial With Pyrimethamine, Lenalidomide, TOpiramate
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.
Read the detailed description
Rationale Though combined antiretroviral therapy (ART) has made HIV a clinically manageable chronic illness by preventing viral replication, HIV poses great burdens on PLWH and society to this day. Due to the presence of a stable, latent viral reservoir, the virus rebounds when ART is stopped. Additionally this reservoir fuels inflammation with related comorbidities. Finding therapies to reduce the reservoir are therefore an important research objective. One strategy to shrink or eliminate the latent reservoir aims to reverse the reservoir from latency, leading to increased antigen presentation and trigger immune recognition (the "shock and kill" strategy). Several latency reversal agents (LRA) have been identified. Though single LRA treatment are effective to a limited extent, they have not resulted in significant HIV reservoir reduction. PLUTO, aims to study novel combinations of promising LRAs with different targets to reactivate and reduce the latent viral reservoir by identifying the combination with strongest latency reversal of phase I of our study and assessing latency reversal and reservoir decay after prolonged treatment in phase II of our study.
Objectives
Primary objectives phase I:
- To assess the efficacy of LRA combinations during a one day treatment on HIV reservoir reactivation in people living with HIV.
Primary objectives phase II:
- Efficacy of dual LRA combination treatments on HIV reservoir reduction.
Main trial endpoints
Phase I Primary endpoint:
- Fold change in cell-associated HIV-RNA at time points 6, and 24 hours compared to baseline
Phase II Primary endpoint:
- Log transformed HIV-DNA at T=4w compared to T=0
Trial design Proof of concept two-phase sequential randomized controlled trial. Phase I consists of three arms receiving a single dose combination treatment, with a 7-day follow-up.
Phase II consists of a single arm receiving a four-week treatment with the selected treatment from phase I, and a with a total follow-up duration of five weeks.
Trial population Phase I 30 people with HIV-1 with inclusion criteria: ≥18years of age, plasma HIV-RNA >1000c/mL before ART, current plasma HIV-RNA <50c/ml for at least two measurements on uninterrupted ART and current CD4+T-cells > 200/mm3.
Phase II A minimum of 16 people with HIV-1 with the same inclusion criteria. All participants from phase I are eligible, and may move on to, phase II with additional consent. In case the required number of participants are not reached from phase I, new participants can be recruited following the same selection procedure as in phase I.
Interventions Phase I The investigational drugs are Pyrimethamine, Lenalidomide, and Topiramate. Patients will be randomized 1:1:1 in one of three arms to receive a single dose of LRA combination of two investigational drugs
Phase II Compound combination with highest latency reversing potential, within safety limits and taking patient participant preference into account is the phase II intervention. Dosing is adjusted to achieve steady state concentrations similar to phase I.
- Being tested
- Pyrimethamine (PYR), Lenalidomide, Topiramate (drug)
- Keywords
- HIV, HIV reservoir, Latency Reversing Agent, HIV cure, Topiramate, Pyrimethamine, Lenalidomide
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyrimethamine (PYR)Drug
Pyrimethamine is a registered antiprotozoal agent, which is used for treating toxoplasmosis and malaria. As a latency reversing agent it exerts its effect by targeting the BAF chromatin remodeling complex involved in maintaining a transcriptional repression.
LenalidomideDrug
Lenalidomide is a registered immunomodulatory drug, registered for multipel myeloma, lymphoma's and Kaposi Sarcoma. As an LRA it targets transcription factor IKZF1, a transcriptional repressor.
Topiramate (drug)Drug
Topiramate is a drug registered to for migraine prophylaxis and epilepsy. It binds to GRIK5 at the proviral promotor and inhibits its function. GRIK5 derepresses virus transcription initiation with latency reversal as a result.
| Study group | Role | What they receive |
|---|---|---|
| PYR + LENA | Experimental | Pyrimethamine 200mg oral administration + Lenalidomide 25mg oral administration Receives: Drug: Pyrimethamine (PYR); Drug: Lenalidomide |
| PYR + TOPI | Experimental | Pyrimethamine 200mg oral administration + Topiramate 400mg oral administration Receives: Drug: Pyrimethamine (PYR); Drug: Topiramate (drug) |
| LENA + TOPI | Experimental | Lenalidomide 25mg oral administration + Topiramate 400 mg oral administration Receives: Drug: Lenalidomide; Drug: Topiramate (drug) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I primary outcome: Fold change in cell-associated HIV-RNA
The fold change in cell-associated HIV-RNA within and between the study arms
Measured: At time points 6 and 24 hours after treatment, compared to baseline
Phase II primary outcome: Log transformed HIV-DNA
The change in log transformed HIV-DNA within the treatment group. Measured using IPDA and SQuHIVLa
Measured: At time point 4 weeks compared to baseline
Secondary outcomes (19)
Phase I & II: Clinical safety and tolerability of the LRA drug combination.
The number and severity of clinical and biochemical adverse events assessed using Common Terminology Criteria for Adverse Events version 6
Measured: Phase I: 1 week Phase II: 5 weeks
Phase I: Participant preference on the latency reversing agent (LRA) combinations.
Participant preference for LRA combinations, quantitatively assessed using a pill diary with Likert scales 1-5 (higher scores meaning better outcome)
Measured: At 0 hours, 24 hours and 7 days
Phase I: Participant quality of life during combination LRA treatment
To evaluate qualitative patient reported outcomes of quality of life assessed by semi-structured interviews
Measured: Baseline, and at timepoint 7 days
Phase I: Plasma HIV-RNA kinetics during interventional treatment
Change in plasma HIV-RNA between and within arms
Measured: At time points 6 hours, 24 hours and 7 days compared to baseline
Phase I: Change of the functionality of immune cells
The change of the functionality of innate and adaptive immune cell subpopulations, specifically total T cells and HIV specific CD4+ and CD8+ T cells as well as HIV specific antibody profiles, between and within the groups
Measured: At 7 days, compared to baseline
Phase I: Change of the phenotype of immune cells
The change of the phenotype of innate and adaptive immune cell subpopulations, specifically total T cells and HIV specific CD4+ and CD8+ T cells as well as HIV specific antibody profiles, between and within the groups
Measured: At 7 days, compared to baseline
Phase I: Pharmacokinetics of LRA compounds
Plasmaconcentrations Cmax will be measured using validated methods and related to the primary endpoint
Measured: At time points 2 hours, 6 hours, 24 hours and 7 days compared to baseline
Phase I: Pharmacokinetics of LRA compounds
Plasmaconcentrations Cthrough will be measured using validated methods and related to the primary endpoint
Measured: At time points 2 hours, 6 hours, 24 hours and 7 days compared to baseline
Phase I: Drug plasma levels of ART
Plasma concentrations Cmax of ART (antiretroviral therapy) will be measured using validated methods and related to LRA compounds
Measured: At time points 0 hours, 6 hours, 24 hours and 7 days
Phase I: Drug plasma levels of ART
Description: Plasma concentrations Cthrough of ART (antiretroviral therapy) will be measured using validated methods and related to LRA compounds
Measured: At baseline and at time points 6 hours, 24 hours and 7 days
Phase I: Ex vivo/ In vivo correlation of reservoir reactivation
The correlation between ex vivo and in vivo fold change in cell-associated HIV-RNA
Measured: From time points baseline to 24 hours
Phase II: Participant quality of life during LRA combination treatment.
To evaluate qualitative patient reported outcomes of quality of life assessed by semi-structured interviews
Measured: At baseline and timepoint 4 weeks
Phase II: Plasma HIV-RNA kinetics during interventional treatment
Change in plasma HIV-RNA absolute copies/mL within groups
Measured: At timepoints 24 hours, 1 week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: functionality of innate and adaptive immune cells
The change of the functionality of innate and adaptive immune cell subpopulations, specifically total T cells and HIV specific CD4+ and CD8+ T cells as well as HIV specific antibody profiles, between and within the groups
Measured: At time points 1 week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: Phenotype of innate and adaptive immune cells
The change of the phenotype of innate and adaptive immune cell subpopulations, specifically total T cells and HIV specific CD4+ and CD8+ T cells as well as HIV specific antibody
Measured: At time points 1 week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: Pharmacokinetics LRA compounds
Plasmaconcentrations Cmax will be measured using validated methods and related to the primary endpoint
Measured: At time points 1 week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: Pharmacokinetics of LRA compounds
Plasmaconcentrations Cthrough will be measured using validated methods and related to the primary endpoint
Measured: At time points 1week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: Drug plasma levels of ART
Plasma concentrations Cmax of ART will be measured using validated methods. The pharmacokinetic profiles ART will be assessed in relation to the primary endpoint and LRA compounds
Measured: At time points 1 week, 2 weeks, 3 weeks and 4 weeks
Phase II: Drug plasma levels of ART
Description: Plasma concentrations Cthrough of ART will be measured using validated methods. The pharmacokinetic profiles ART will be assessed in relation to the primary endpoint and LRA compounds
Measured: At time points 1 week, 2 weeks, 3 weeks, 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2026
- Study startApr 2026 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV (Human Immunodeficiency Virus)Studies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Proof of concept two-phase sequential randomized controlled trial Phase I consists 3 arms of a single dose combination treatment, with a 7-day follow-up. Phase II consists of a single arm four-week treatment, with a total follow-up duration of five weeks.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Casper Rokx, Erasmus Medical Center
- Investigators
- Casper Rokx, MD PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07384624
- Sponsor's protocol ID
- 2026-525211-14-00.
- Other IDs
- 2026-525211-14-00
- Acronym
- PLUTO
- Status last verified
- Jan 2026
- First submitted
- 8 Jan 2026
- Last updated
- 3 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be stored under FAIR use principle for use in future research. Should external researchers want to use this dataset, they can contact the principal investigator. In the case of adequate privacy standards data can be shared under a specific new Data Sharing Agreement
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Curing HIV: Proof of Concept Randomized Clinical Trial With Pyrimethamine, Lenalidomide, TOpiramate
- ClinicalTrials.gov ID
- NCT07384624
- Acronym / sponsor ID
- PLUTO / 2026-525211-14-00.
- Keywords
- HIV, HIV reservoir, Latency Reversing Agent, HIV cure, Topiramate, Pyrimethamine, Lenalidomide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- Apr 2026 (estimated)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 3 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Rationale Though combined antiretroviral therapy (ART) has made HIV a clinically manageable chronic illness by preventing viral replication, HIV poses great burdens on PLWH and society to this day. Due to the presence of a stable, latent viral reservoir, the virus rebounds when ART is stopped. Additionally this reservoir fuels inflammation with related comorbidities. Finding therapies to reduce the reservoir are therefore an important research objective. One strategy to shrink or eliminate the latent reservoir aims to reverse the reservoir from latency, leading to increased antigen presentation and trigger immune recognition (the "shock and kill" strategy). Several latency reversal agents (LRA) have been identified. Though single LRA treatment are effective to a limited extent, they have not resulted in significant HIV reservoir reduction. PLUTO, aims to study novel combinations of promising LRAs with different targets to reactivate and reduce the latent viral reservoir by identifying the combination with strongest latency reversal of phase I of our study and assessing latency reversal and reservoir decay after prolonged treatment in phase II of our study.
Objectives
Primary objectives phase I:
- To assess the efficacy of LRA combinations during a one day treatment on HIV reservoir reactivation in people living with HIV.
Primary objectives phase II:
- Efficacy of dual LRA combination treatments on HIV reservoir reduction.
Main trial endpoints
Phase I Primary endpoint:
- Fold change in cell-associated HIV-RNA at time points 6, and 24 hours compared to baseline
Phase II Primary endpoint:
- Log transformed HIV-DNA at T=4w compared to T=0
Trial design Proof of concept two-phase sequential randomized controlled trial. Phase I consists of three arms receiving a single dose combination treatment, with a 7-day follow-up.
Phase II consists of a single arm receiving a four-week treatment with the selected treatment from phase I, and a with a total follow-up duration of five weeks.
Trial population Phase I 30 people with HIV-1 with inclusion criteria: ≥18years of age, plasma HIV-RNA >1000c/mL before ART, current plasma HIV-RNA <50c/ml for at least two measurements on uninterrupted ART and current CD4+T-cells > 200/mm3.
Phase II A minimum of 16 people with HIV-1 with the same inclusion criteria. All participants from phase I are eligible, and may move on to, phase II with additional consent. In case the required number of participants are not reached from phase I, new participants can be recruited following the same selection procedure as in phase I.
Interventions Phase I The investigational drugs are Pyrimethamine, Lenalidomide, and Topiramate. Patients will be randomized 1:1:1 in one of three arms to receive a single dose of LRA combination of two investigational drugs
Phase II Compound combination with highest latency reversing potential, within safety limits and taking patient participant preference into account is the phase II intervention. Dosing is adjusted to achieve steady state concentrations similar to phase I.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Proof of concept two-phase sequential randomized controlled trial Phase I consists 3 arms of a single dose combination treatment, with a 7-day follow-up. Phase II consists of a single arm four-week treatment, with a total follow-up duration of five weeks.
| Arm | Type | Receives |
|---|---|---|
| PYR + LENA | Experimental | Drug: Pyrimethamine (PYR), Drug: LenalidomidePyrimethamine 200mg oral administration + Lenalidomide 25mg oral administration |
| PYR + TOPI | Experimental | Drug: Pyrimethamine (PYR), Drug: Topiramate (drug)Pyrimethamine 200mg oral administration + Topiramate 400mg oral administration |
| LENA + TOPI | Experimental | Drug: Lenalidomide, Drug: Topiramate (drug)Lenalidomide 25mg oral administration + Topiramate 400 mg oral administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyrimethamine (PYR)Pyrimethamine is a registered antiprotozoal agent, which is used for treating toxoplasmosis and malaria. As a latency reversing agent it exerts its effect by targeting the BAF chromatin remodeling complex involved in maintaining a transcriptional repression. | Drug | PYR + LENA, PYR + TOPI |
| LenalidomideLenalidomide is a registered immunomodulatory drug, registered for multipel myeloma, lymphoma's and Kaposi Sarcoma. As an LRA it targets transcription factor IKZF1, a transcriptional repressor. | Drug | LENA + TOPI, PYR + LENA |
| Topiramate (drug)Topiramate is a drug registered to for migraine prophylaxis and epilepsy. It binds to GRIK5 at the proviral promotor and inhibits its function. GRIK5 derepresses virus transcription initiation with latency reversal as a result. | Drug | LENA + TOPI, PYR + TOPI |
Primary outcome
Phase I primary outcome: Fold change in cell-associated HIV-RNA
Time frame: At time points 6 and 24 hours after treatment, compared to baseline
The fold change in cell-associated HIV-RNA within and between the study arms
Phase II primary outcome: Log transformed HIV-DNA
Time frame: At time point 4 weeks compared to baseline
The change in log transformed HIV-DNA within the treatment group. Measured using IPDA and SQuHIVLa
19 secondary outcomes
Phase I & II: Clinical safety and tolerability of the LRA drug combination.
Time frame: Phase I: 1 week Phase II: 5 weeks
Phase I: Participant preference on the latency reversing agent (LRA) combinations.
Time frame: At 0 hours, 24 hours and 7 days
Phase I: Participant quality of life during combination LRA treatment
Time frame: Baseline, and at timepoint 7 days
Phase I: Plasma HIV-RNA kinetics during interventional treatment
Time frame: At time points 6 hours, 24 hours and 7 days compared to baseline
Phase I: Change of the functionality of immune cells
Time frame: At 7 days, compared to baseline
Phase I: Change of the phenotype of immune cells
Time frame: At 7 days, compared to baseline
Phase I: Pharmacokinetics of LRA compounds
Time frame: At time points 2 hours, 6 hours, 24 hours and 7 days compared to baseline
Phase I: Pharmacokinetics of LRA compounds
Time frame: At time points 2 hours, 6 hours, 24 hours and 7 days compared to baseline
Phase I: Drug plasma levels of ART
Time frame: At time points 0 hours, 6 hours, 24 hours and 7 days
Phase I: Drug plasma levels of ART
Time frame: At baseline and at time points 6 hours, 24 hours and 7 days
Phase I: Ex vivo/ In vivo correlation of reservoir reactivation
Time frame: From time points baseline to 24 hours
Phase II: Participant quality of life during LRA combination treatment.
Time frame: At baseline and timepoint 4 weeks
Phase II: Plasma HIV-RNA kinetics during interventional treatment
Time frame: At timepoints 24 hours, 1 week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: functionality of innate and adaptive immune cells
Time frame: At time points 1 week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: Phenotype of innate and adaptive immune cells
Time frame: At time points 1 week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: Pharmacokinetics LRA compounds
Time frame: At time points 1 week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: Pharmacokinetics of LRA compounds
Time frame: At time points 1week, 2 weeks, 3 weeks and 4 weeks compared to baseline
Phase II: Drug plasma levels of ART
Time frame: At time points 1 week, 2 weeks, 3 weeks and 4 weeks
Phase II: Drug plasma levels of ART
Time frame: At time points 1 week, 2 weeks, 3 weeks, 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2026.
- Individual participant dataSharing planned: Yes. Data will be stored under FAIR use principle for use in future research. Should external researchers want to use this dataset, they can contact the principal investigator. In the case of adequate privacy standards data can be shared under a specific new Data Sharing Agreement
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniek Teijema, MD contact
Casper Rokx, MD PhD principal investigator
Erasmus Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pyrimethamine (PYR), Lenalidomide and Topiramate (drug) in people with HIV (Human Immunodeficiency Virus) and HIV -1 Infection, run by Erasmus Medical Center at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Casper Rokx, MD PhD (+31681336328, c.rokx@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I primary outcome: Fold change in cell-associated HIV-RNA (time frame: At time points 6 and 24 hours after treatment, compared to baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2026.