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Study of Baricitinib and Sirolimus to Maintain HIV Infection Control After Antiretroviral Treatment Interruption in Adults

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on people living with HIV-1 Infection who are currently taking antiretroviral medication (ART). It tests two existing drugs, an mTORC1 inhibitor called sirolimus and a JAK1/JAK2 inhibitor called baricitinib, either alone or together, and compares them with an inactive tablet (placebo). The purpose is to see whether these medicines can help keep the virus under control without the need to resume ART after a planned break.

Participants who meet the study criteria stop their regular ART for a short, supervised period. During this time they are randomly assigned to receive either sirolimus, baricitinib, the two drugs combined, or a placebo. Regular clinic visits include simple blood tests to check the amount of virus (viral load) and the number of important immune cells called CD4 T cells, which help the body fight infections. If the virus level rises sharply (viral rebound) or CD4 T cells drop too low, the participant restarts ART as advised by the medical team.

The trial follows each person for several months, tracking how long they stay off ART, changes in virus levels, and any side effects from the study drugs. Safety checks are performed throughout, and the overall goal is to determine whether the experimental immunotherapies are safe and can keep the infection controlled without continuous ART.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Baseline Visit and Randomization (Week 0)

    At the first visit you will have blood drawn to measure your CD4 count and viral load. After these tests you will be randomly assigned to receive either sirolimus, baricitinib, the combination of both, or matching placebos. Your regular antiretroviral therapy (ART) will be stopped at this time, beginning the treatment interruption.

  2. Step 2

    Start of Study Medication (Week 0)

    If you are assigned to an active arm, you will begin taking the study drug(s) immediately after the baseline visit. Sirolimus is taken orally at a dose of 2 mg once daily. Baricitinib is taken orally at a dose of 2 mg once daily. If you are in the combination arm, you will take both tablets each day. The medication is continued daily until the end of the study period or until your doctor advises stopping it.

  3. Step 3

    Safety Check (Week 2)

    Two weeks after starting the medication you will return for a safety visit. Blood samples will be collected to monitor your CD4 count, viral load, and any possible side effects. The study team will decide whether you should continue the medication as planned.

  4. Step 4

    Mid‑Study Assessment (Week 10)

    At week 10 you will have another clinic visit. The visit includes blood tests to evaluate changes in CD4 and CD8 counts, and to measure your viral load. The results help determine how the medication is affecting your immune system and the virus. You will continue taking the study drug(s) unless a safety concern requires discontinuation.

  5. Step 5

    Primary Evaluation (Week 26)

    Week 26 is the primary evaluation point of the trial. Blood tests are performed again to assess CD4 count, viral load, and other immune markers. If your viral load rises sharply (viral rebound) or your CD4 count falls below the predefined safety threshold, you will be instructed to restart ART. The decision to continue or stop the study medication is also reviewed at this visit.

  6. Step 6

    Extended Follow‑Up (Week 50)

    At week 50 you will attend a final follow‑up visit. This visit repeats the laboratory assessments performed at earlier visits and records any long‑term effects of the medication. If you have remained off ART and the medication has not been discontinued, you will continue taking the study drug(s) until this visit.

  7. Step 7

    Restart of ART (If Required)

    At any point during the study, if your viral load reaches 1,000 copies per milliliter or higher, or if your CD4 count drops to a level that raises safety concerns, you will be asked to restart your regular antiretroviral therapy (ART). Restarting ART ends the treatment interruption phase for you, but you will continue to be monitored according to the study schedule.

Who can join the trial?

18 criteria

  • Must be able to understand what the study involves and sign a consent form.
  • Must be taking HIV medicines (called ART) that include dolutegravir (DTG), bictegravir (BIC), raltegravir (RAL) or rilpivirine (RPV) together with at least one other type of HIV drug, or a combination of DTG and RPV. If you are using other HIV medicines (such as protease inhibitors, elvitegravir, nevirapine, efavirenz, etravirine, or doravirine), you must switch to one of the listed medicines by week 8.
  • Your blood must show a CD4 T‑cell count of at least 500 cells per microliter on the two most recent tests. (CD4 cells are a type of immune cell that HIV can affect.)
  • You must be willing to stop your HIV medicines temporarily (called an analytical treatment interruption) and, if needed, change them before receiving the study drug to avoid interactions.
  • You must agree to take one tablet of valaciclovir 500 mg each day from the start of the study (week 0) through week 10 to help prevent herpes or shingles.
  • You must use a reliable method to lower the risk of HIV transmission with sexual partners (such as condoms or having your partner use PrEP) during the treatment interruption and until your viral level is undetectable again.
  • If you were assigned female at birth and could become pregnant, you must agree to regular pregnancy tests (β‑HCG testing) before the study, at the start, and at least each month thereafter, and you must use highly effective birth control from the start until 12 weeks after stopping the study drug. You also must avoid trying to become pregnant, including using assisted reproductive technologies, during this time.
  • If you were assigned male at birth and are sexually active with women, you must agree to use condoms or ensure your partner uses effective birth control (and PrEP if needed) from the start until 12 weeks after stopping the study drug, and you must not donate sperm during this period.
  • You must be willing to attend all scheduled study visits and have blood drawn as required.
  • You must have health coverage through social security insurance.
  • You must sign a written informed consent form together with the study investigator before any study procedures begin.
  • You must be between 18 and 65 years old.
  • Your body weight must be between 50 kg and 100 kg.
  • You must have been diagnosed with HIV‑1 during the very early (primary) infection stage, with a viral load (amount of virus in the blood) higher than 1,000 copies/mL, and you must have had a negative or incomplete Western blot (WB), immunoblot (IB) or ELISA test within the past 3 months.
  • You must have started HIV treatment (ART) within 2 months after that early diagnosis.
  • You must have taken your HIV medicines continuously without any breaks.
  • You must have been on HIV treatment for at least 1 year before joining the study (changing medicines is allowed as long as the virus does not rebound).
  • Your HIV viral load must have been less than 50 copies/mL for at least 6 months before joining, with at least two separate tests showing this level. One small temporary increase (called a “blip”) up to 200 copies/mL is allowed if it returns to below 50 copies/mL within 15 days.

Who cannot join the trial?

32 criteria

  • Participant unlikely, in the investigator’s view, to follow study steps or whose overall health makes participation unsafe.
  • Pregnant or breastfeeding woman.
  • Woman who plans to become pregnant during the study period.
  • History or other condition that makes stopping HIV medication (ART) unsafe.
  • History of heart disease, stroke, blood clots (venous or arterial thrombosis), clotting disorders (thrombophilia), or other risk factors for clotting (combined estrogen‑progestin birth control is allowed).
  • High risk of heart problems measured by SCORE2 (>7.5% if under 50 years old, or >10% if 50‑65 years old).
  • Active cancer or past cancer, except certain skin cancers or cancers cured by surgery more than 5 years ago; also any history of chemotherapy or radiation.
  • Active opportunistic infection (infection that takes advantage of a weakened immune system).
  • History of HIV‑associated dementia or the rare brain infection called progressive multifocal leukoencephalopathy.
  • Active or untreated tuberculosis (TB), except if already treated for latent TB; a TB screen is required before joining.
  • Chronic hepatitis B (positive surface antigen), past hepatitis B infection (specific blood test pattern), chronic hepatitis C (detectable virus), or any liver scarring (cirrhosis).
  • HIV‑2 infection.
  • Use of systemic steroids, other immune‑suppressing medicines, immune‑modulating drugs, or continuous NSAIDs within 12 weeks before randomization; also anyone who ever received an anti‑CD20 antibody (a type of cancer drug).
  • History of solid organ transplantation (e.g., kidney, liver) or bone‑marrow transplantation.
  • Any vaccination received within the last 30 days or planned during the study.
  • Previous participation in an experimental HIV vaccine trial.
  • Use of medicines that affect liver enzymes CYP3A4 or transporter P‑gp, or any drug that changes how the study medicines are processed, within 2 weeks before randomization.
  • Known allergy to macrolide antibiotics.
  • Rare inherited problems with processing certain sugars (e.g., fructose intolerance, galactose intolerance, glucose‑galactose malabsorption, sucrase‑isomaltase deficiency, Lapp lactase deficiency).
  • Ongoing treatment at the start of the study with any of the following: medicines that speed up gut movement (such as metoclopramide), strong OAT3 inhibitors (e.g., probenecid), cimetidine (which can interact with valaciclovir), or cannabidiol (which can interact with sirolimus).
  • Allergy to sirolimus, baricitinib, valaciclovir, acyclovir, or any ingredient in the study drugs.
  • Receiving State Medical Aid (AME) benefits.
  • History of stopping HIV medication (ART) in the past.
  • Under legal guardianship or detained by a court decision (unless there is a justified reason).
  • Participation in another interventional clinical trial at the same time (observational studies without blood draws are allowed).
  • Laboratory results outside allowed ranges before joining: very low neutrophils, low hemoglobin, low platelets, severely reduced kidney function (eGFR <30 mL/min/1.73 m²), low blood clotting time (prothrombin <50%), very high liver enzymes (ALT/AST >5 × upper limit), or very high bilirubin (>3 × upper limit).
  • HIV viral load failure: more than 200 copies/mL confirmed on two tests, except a single small rise (50‑200 copies/mL) within the past 6 months that was quickly controlled.
  • Use of long‑acting HIV medicines such as cabotegravir/rilpivirine, lenacapavir, islatravir, or ibalizumab.
  • Taking HIV medication only on 4‑5 days per week instead of daily.
  • Current HIV regimen includes certain drugs (protease inhibitors, EVG/c, nevirapine, efavirenz, etravirine, or doravirine) after week‑8.
  • No alternative HIV treatment options besides the current regimen.
  • Lowest ever recorded CD4 count (CD4 nadir) below 200 cells per microliter.
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Investigated drugs

Sirolimus is a medication that works by gently slowing down a part of the immune system called mTORC1. In this trial, it is being tested to see if it can help keep the amount of HIV in the body low after a person stops their regular antiretroviral medicines. By adjusting the immune response, researchers hope it may reduce the virus’s ability to multiply.

Baricitinib is a drug that blocks signals from proteins known as JAK1 and JAK2, which are involved in how immune cells react. The study is checking whether this medication can help control HIV replication after stopping antiretroviral treatment by moderating the immune system’s activity.

The combination therapy uses both Sirolimus and Baricitinib together. The idea is that the two different ways of influencing the immune system might work better side‑by‑side, giving a stronger or more lasting control of HIV when a person is off their regular HIV medicines.

What is already known about the treatment

  • Sirolimus

    This medication is taken by mouth as a tablet, usually 2 mg taken once daily. It is an approved drug used to prevent organ transplant rejection and to treat certain rare cancers, and it is also being studied for its potential to control HIV when treatment is stopped. Sirolimus works by blocking a protein called mTOR, which slows down cell growth and the activity of the immune system. It belongs to the class of medicines known as mTOR inhibitors and is considered an immunosuppressant.

  • Baricitinib

    Baricitinib is an oral, film‑coated tablet taken at a dose of 2 mg once daily. It is already approved for treating rheumatoid arthritis and is being examined for its ability to help keep HIV under control after stopping standard therapy. The drug blocks the activity of JAK1 and JAK2 enzymes, which reduces signals that cause inflammation and immune activation. Baricitinib is classified as a JAK inhibitor and is a type of disease‑modifying antirheumatic drug (DMARD).

Investigated diseases

HIV-1 infection - HIV-1 infection is a viral disease caused by the human immunodeficiency virus type 1. The virus primarily targets immune cells called CD4 T‑lymphocytes, entering and replicating inside them. Over time the number of functional CD4 cells declines, which reduces the body's ability to fight common infections. As the immune system weakens, individuals may experience more frequent or severe infections, inflammation, and other health changes.
Trial detailsLast updated 29 Oct 2026
Age18+ yearsPhasePhase IITrial ID2025-523118-97-00Protocol code0668s RHIVIERA-03Estimated enrolment195 patientsSponsorANRS Maladies Infectieuses Emergentes

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