Study not started as the IMP is re-worked by the manufacturer

The UNIVERSAL2 study is a research project designed to evaluate a newly developed formulation of an approved drug for children living with HIV aged over 3 years and weighing between 10 and 25 kg. The aim of UNIVERSAL2 is to determine the right dosage of this new formulation.

The UNIVERSAL2 study is a research project designed to evaluate a newly developed formulation of an approved drug for children living with HIV aged over 3 years and weighing between 10 and 25 kg. The aim of UNIVERSAL2 is to determine the right dosage of this new formulation.

It is a combination of two anti-HIV medicines called darunavir (DRV) and ritonavir (RTV). The DRV/RTV combination is well known and has been used for a long time in adults and children to treat HIV infection but there is no combined pediatric formulation that has been adapted to the needs of children ("child friendly" formulation).

The new combination has been developed in the form of fixed-dose combination tablets with a dose of 120 mg of DRV and 20 mg of RTV (DRV/RTV 120/20) in each tablet. Depending on their weight and the need to take the medication once or twice a day, children may receive 2, 3 or 4 DRV/RTV 120/20 tablets at any given time.

The aim of UNIVERSAL2 is to determine the correct dosage and to assess the safety and acceptability of the new drug for children living with HIV.

The study will focus on two groups of children.

• Group A will include children with one or two specific viral genetic mutations linked to DRV resistance and will receive DRV/RTV twice daily.
• Group B will include children without DRV resistance viral gene mutations who will receive DRV/RTV once daily.

All children will start taking the DRV/r at the beginning of the study. After two weeks, participants will be invited to stay at the clinic for blood samples to be taken at different times of the day in order to understand how the drug is absorbed, metabolised and excreted in the body (pharmacokinetic tests). They will then continue to be monitored at the clinic several times over a 24-week period, with additional blood tests to be sure children are tolerating the drug well and that it helps to control HIV replication. Participants and their carers will also be asked to answer some questions to determine how acceptable the new tablets are to children and carers.

Inclusion Criteria:

• • Confirmed HIV-1 infection

  • Aged ≥ 3 years
  • With unsuppressed viral load (HIV-1 RNA viral load > 1000 c/mL) on ART-regimen and eligible to switch to new DRV/r 120/20 mg-based regimen per investigator's judgement
  • Able to swallow the 120/20 mg DRV/r tablets
  • Willing to receive the 120/20 mg DRV/r tablets
  • Parents or guardians, and children where appropriate, willing and able to give informed consent and to adhere to the protocol
  • Cohort-specific inclusion criteria:

Cohort A:

• Have 1 or 2 DRV resistance-associated mutations (RAMs)*
• Weigh 10 to <25 kg at screening

Cohort B:

• Have no DRV RAMs*
• Weigh 10 to <20 kg at screening. *DRV RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V

Exclusion Criteria:

• Presence of >2 darunavir RAMs*

  • Failure of protease genotypic resistance testing at baseline, except if treatment history indicates that it is very unlikely
  • Resistance to all NRTI available in the country or impossibility to define an OBT
  • Intercurrent illness (enrolment can take place after the illness resolves)
  • Creatinine ≥ 1.8 Upper Limit of Normal (ULN) or ALT ≥ 5 ULN or (ALT ≥ 3 ULN and bilirubin ≥2 ULN) at screening.
  • Severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • History or presence of known allergy or other contraindication to DRV/r or their components as described in the Summary of Product Characteristics (SmPC)
  • Concomitant medications that may interact with the current antiretroviral treatment, in particular TB drugs (i.e: rifampicin, rifabutin, rifapentine, …).