Evaluation of Low-dose Darunavir in a Switch Study
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a switch study to assess the non-inferiority (in terms of efficacy and safety) of
      darunavir (boosted with ritonavir, DRV/r 400mg/100mg daily) when compared with lopinavir
      (boosted with ritonavir, LPV/r total dose 800mg/200mg daily), in combination with a
      nucleoside backbone, administered as a second line therapy in HIV positive individuals.
    

Detailed description: 
      This is an open label randomised, parallel group, phase 3b, switch study to demonstrate
      non-inferiority of low-dose boosted darunavir (DRV/RTV 400/100 mg once daily) compared with
      boosted lopinavir-based (LPV/RTV 800/200 mg daily) second-line regimens when administered
      over 48 weeks in combination with two nucleos(t)ide reverse transcriptase inhibitors in
      patients infected with HIV-1 who are virologically suppressed and stable on a standard
      second-line regimen. All medications will be provided in an open-label design. Patients who
      are virologically suppressed and stable on a standard second-line regimen will be recruited
      for the study. There are concerns that switching these patients may result in virological
      failure as the study aimed at demonstrating non-inferiority of darunavir compared with
      Lopinavir. In such cases, the investigator will ensure that virological failures are
      investigated and patients are switched back to standard of care immediately. Participants
      will be patients who are receiving HIV treatment in public clinics. Interested patients will
      be invited to the study, information given, and only those who will give written informed
      consent will be screened, and if eligible enrolled into the study. Each enrolled participant
      will be follow-up at week 4, 12, 24, 36, and 48 (exit visit) from enrolment date. Data will
      be collected using ethics-approved worksheets, and captured into REDCap. The data manager
      will ensure data are correct and complete by performing data verifications - physical and
      electronic. Internal quality control will be performed by dedicated staff based on the study
      quality plan to be implemented. The external study monitor will perform 100% eligibility
      checks on all signed informed consents in addition to other source verifications during her
      periodic site visits according to the monitoring plan to be implemented. Findings from the
      monitor will be implemented in the form of data/procedure corrections per good clinical
      practice, and all relevant staff trained and documented accordingly. Participants' records
      will be coded and stored in a lockable cabinet. Only study staff will have access to
      participants' records. All electronic documents relating to the study will be stored in
      password-protected computers and only accessible to study staff. Study staff are not allowed
      to share password among themselves or with anyone outside the study team. Designed in
      non-inferiority fashion, this study will enrol approximately 300 participants for 80% power
      to detect a 10% non-inferiority margin in the per protocol (PP) analysis. A Data Safety
      Management Board (DSMB) will oversee and review the interim data report. At the close of the
      study, results will be disseminated to participants, and the scientific community, as well as
      updated on clinicaltrial.gov.
    

Intervention name(s): Darunavir; Lopinavir
Intervention type(s): Drug; Drug
Intervention description(s): Darunavir/ritonavir 400/100mg (DRV/r) once daily plus nucleoside/nucleotide reverse transcriptase inhibitors.; Lopinavir/ritonavir 400/100mg (LPV/r) twice daily plus nucleoside/nucleotide reverse transcriptase inhibitors.
Other intervention name(s): Boosted darunavir (DRV/r); Boosted lopinavir (LVP/r)
Intervention MeSH terms: Lopinavir; Darunavir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Antiretroviral Agents; Treatment; Viral Load