Human Immunodeficiency Virus (HIV) Postexposure Prophylaxis (PEP) With Darunavir/Ritonavir (DRV/r)

Phase 3

Completed

• Conditions: Human Immunodeficiency Virus (HIV)
• Interventions: Drug: Lopinavir in fixed combination with Ritonavir; Drug: Darunavir/Ritonavir (DRV/r); Drug: Zidovudine; Drug: NRTIs; Drug: Efavirenz

• Registration Number: NCT01516970
• Lead Sponsor: Janssen-Cilag G.m.b.H

Brief Summary

The primary purpose of this study is to assess the rate of early discontinuation from randomized Human Immunodeficiency Virus (HIV) Postexposure Prophylaxis (PEP) for any reason other than confirmation of the negative HIV infection status of the index person in patients receiving HIV PEP for at least 28 and a maximum of 30 days.

Detailed Description

This is a randomized (study medication assigned by chance), open-label (all people involved know the identity of the intervention), active-controlled (patients are assigned to either a recognized effective treatment or the study medication), parallel-group (each treatment group will be treated at the same time), multicenter study comparing DRV/r PEP (DRV/r administered with 2 NRTIs selected at the discretion of the investigator) to standard of care PEP (as per German-Austrian guidelines) in patients at risk of HIV infection due to HIV exposure through occupational injury and non-occupational exposure. This study consists of screening period, treatment period and a follow up period. HIV PEP will be administered for a total of at least 28 days and maximum of 30 days during treatment period, including any prestudy HIV PEP initiated before screening. Approximately 318 patients will be screened and enrolled to ensure that at least 131 patients are randomly assigned to receive DRV/r PEP or standard of care PEP. Safety will be evaluated during the entire study period. Data relating to a patient's functional impairment in conjunction with HIV PEP will be collected on Day 1 as baseline data, and further on Days 14 and 28 as well as at Month 3.

Study Timeline

• Study First Submitted: 2011-10-11
• Study Start: 2011-11-25
• Study First Submitted QC: 2012-01-20
• Study First Posted: 2012-01-25
• Primary Completion: 2013-08-01
• Study Completion: 2013-09-28
• Disposition First Submitted: 2014-06-27
• Disposition First Submitted QC: 2014-06-27
• Disposition First Posted: 2014-06-30
• Results First Submitted: 2016-06-20
• Results First Submitted QC: 2016-08-16
• Results First Posted: 2016-10-11
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-21
• Last Update Posted: 2017-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 312

Inclusion Criteria

• Occupational injury and non-occupational exposure with documented human immunodeficiency virus (HIV) exposure, or potential for HIV exposure
• Indication for HIV postexposure prophylaxis (PEP), as determined by the treating physician and/or the investigator
• Women must be: postmenopausal (for at least 2 years), surgically sterile, using oral contraceptives
• Willing to continue HIV PEP for 28 days

Exclusion Criteria

• Positive HIV rapid test
• History of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastro intestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
• Pregnant or breast-feeding
• Any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Comparator standard of care HIV PEP	Lopinavir in fixed combination with Ritonavir	Comparator standard of care HIV PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner.
Comparator standard of care HIV PEP	NRTIs	Comparator standard of care HIV PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner.
DRV/r with 2 NRTIs	Darunavir/Ritonavir (DRV/r)	DRV/r 800/100 mg q.d. with 2 NRTIs: darunavir (800 mg) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs).
DRV/r with 2 NRTIs	NRTIs	DRV/r 800/100 mg q.d. with 2 NRTIs: darunavir (800 mg) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs).
Comparator standard of care HIV PEP	Zidovudine	Comparator standard of care HIV PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner.
Comparator standard of care HIV PEP	Efavirenz	Comparator standard of care HIV PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Early Discontinuation From Randomized Human Immunodeficiency Virus Postexposure Prophylaxis (HIV PEP)	Up to 30 days	Number of participants with early discontinuation from randomized HIV PEP for any reason other than confirmation of the negative HIV infection status of the index person in participants receiving HIV PEP for at least 28 days and a maximum of 30 days was assessed. Per protocol (PP) population included all participants in modified intention-to-treat (mITT \[defined as all participants who were assigned to receive randomized HIV PEP and were not discontinued due to confirmation of the negative HIV infection status of the index person\]) excluding participants with: No indication for HIV PEP; Initiation of PEP \>72 hours after injury; Discontinuation of HIV PEP due to confirmation of HIV negative status of index person and if index person bears resistant virus against HIV PEP components prescribed; incorrect HIV PEP; no intake of medication.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Up to Month 3	An adverse event (AE) is defined to be non-treatment-emergent if the onset date of the AE was clearly before the date of first HIV PEP administration, otherwise it is considered treatment-emergent.
Worst Sheehan Disability Scale (SDS) Score for the Safety Population	Month 3	The Sheehan Disability Scale (SDS) assesses functional impairment in 3 inter-related domains: work/school, social and family life, using a rating scale for each item ranging from 0 (not at all) to 10 (extremely).
Percentage of Participants Who Developed Detectable HIV Antibodies	At Month 3	Seroconversion rate of HIV antibodies while receiving HIV PEP evaluated as the percentage of participants who developed detectable HIV antibodies (defined as positive) and percentage of participants who had not developed detectable HIV antibodies (defined as negative). Per protocol (PP) population included all participants in mITT (defined as all participants who were assigned to receive randomized HIV PEP and were not discontinued due to confirmation of the negative HIV infection status of the index person) excluding participants with: No indication for HIV PEP; Initiation of PEP \>72 hours after injury; Discontinuation of HIV PEP due to confirmation of HIV negative status of index person and if index person bears resistant virus against HIV PEP components prescribed; incorrect HIV PEP; no intake of medication.