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IVERSAL2: Pharmacokinetics safety and acceptability of DRV/r for children living with HIV

Phase 2
Conditions
HIV/AIDS
Registration Number
PACTR202405769820746
Lead Sponsor
Fondazione Penta ETS
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Pending
Sex
All
Target Recruitment
50
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 DRV/r 120/20 mg tablets
•Willing to receive the DRV/r 120/20 mg 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:
oCohort A:
?Have 1 or 2 DRV resistance-associated mutations (RAMs)*
?Weigh 10 to <25 kg at screening
oCohort 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 darunavir RAMs are 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
•Concomitant medications that may interact with the current antiretroviral treatment, in particular TB drugs (i.e: rifampicin, rifabutin, rifapentine, …).

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
area under the concentration-time curve over the time interval from dosing to 12 hours (AUC0-12) (Cohort A) and from dosing to 24 hours (AUC0-24) (Cohort B);maximum plasma concentration (Cmax) and 12 hours or 24 hours post dose concentrations (C12 or C24) ;Occurrence of the following events:<br>•serious adverse events (SAEs); <br>•adverse events (AEs) of Grade 3 or higher;<br>•treatment related AEs;<br>•AEs leading to treatment discontinuation or modification.<br>
Secondary Outcome Measures
NameTimeMethod
•Acceptability of DRV/r tablets (120/20mg) to children and caregivers assessed through questionnaires and direct observation.;Efficacy: <br>•HIV-1 RNA <50 c/mL and <400 c/mL at week 24<br>•Occurrence of a new or recurrent WHO clinical stage 3 or 4 event<br>•Change in CD4 cell count and percentage from baseline to week 24<br>;Pharmacokinetics:<br>•RTV PK parameters and DRV unbound concentrations<br>
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