Trial Outcomes & Findings for Human Immunodeficiency Virus (HIV) Postexposure Prophylaxis (PEP) With Darunavir/Ritonavir (DRV/r) (NCT NCT01516970)

Last Updated: 2017-07-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

312 participants

Primary outcome timeframe

Up to 30 days

Results posted on

2017-07-19

Participant Flow

Participant milestones

Participant milestones
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual SmPCs at the discretion of either the treating physician or Investigator.
Overall Study STARTED	159	153
Overall Study COMPLETED	141	132
Overall Study NOT COMPLETED	18	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual SmPCs at the discretion of either the treating physician or Investigator.
Overall Study Lost to Follow-up	7	8
Overall Study Adverse Event	1	5
Overall Study Withdrawal by Subject	1	1
Overall Study Other	9	7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) n=159 Participants Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) n=153 Participants Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual SmPCs at the discretion of either the treating physician or Investigator.	Total n=312 Participants Total of all reporting groups
Age, Continuous	34.2 years STANDARD_DEVIATION 9.2 • n=93 Participants	32.3 years STANDARD_DEVIATION 9.3 • n=4 Participants	33.3 years STANDARD_DEVIATION 9.3 • n=27 Participants
Sex: Female, Male Female	28 Participants n=93 Participants	28 Participants n=4 Participants	56 Participants n=27 Participants
Sex: Female, Male Male	131 Participants n=93 Participants	125 Participants n=4 Participants	256 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 30 days

Population: Analysis was performed on PP population.

Outcome measures

Outcome measures
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) n=155 Participants Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) n=150 Participants Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Number of Participants With Early Discontinuation From Randomized Human Immunodeficiency Virus Postexposure Prophylaxis (HIV PEP)	10 participants Interval 3.5 to 11.5	15 participants Interval 6.2 to 15.8

SECONDARY outcome

Timeframe: Up to Month 3

Population: The safety population included all participants who received at least 1 dose of randomized HIV PEP.

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.

Outcome measures

Outcome measures
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) n=159 Participants Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) n=153 Participants Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	131 participants	125 participants

SECONDARY outcome

Timeframe: Month 3

Population: The safety population included all participants who received at least 1 dose of randomized HIV PEP.

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).

Outcome measures

Outcome measures
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) n=159 Participants Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) n=153 Participants Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Worst Sheehan Disability Scale (SDS) Score for the Safety Population Impairment in work/school/studies	2.566 units on a scale Standard Deviation 2.775	3.503 units on a scale Standard Deviation 2.940
Worst Sheehan Disability Scale (SDS) Score for the Safety Population Impairment in social life	2.465 units on a scale Standard Deviation 2.594	3.464 units on a scale Standard Deviation 2.786
Worst Sheehan Disability Scale (SDS) Score for the Safety Population Impairment in family life	2.226 units on a scale Standard Deviation 2.624	2.954 units on a scale Standard Deviation 2.713

SECONDARY outcome

Timeframe: At Month 3

Population: Analysis was performed on PP population. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) n=138 Participants Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) n=133 Participants Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Percentage of Participants Who Developed Detectable HIV Antibodies Negative	99.3 percentage of participants	100 percentage of participants
Percentage of Participants Who Developed Detectable HIV Antibodies Positive	0.7 percentage of participants	0 percentage of participants

Adverse Events

Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP)

Serious events: 1 serious events

Other events: 96 other events

Deaths: 0 deaths

Standard of Care Postexposure Prophylaxis (SOCPEP)

Serious events: 0 serious events

Other events: 111 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) n=159 participants at risk Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) n=153 participants at risk Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual SmPCs at the discretion of either the treating physician or Investigator.
Psychiatric disorders Depression	0.63% 1/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	0.00% 0/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.

Other adverse events

Other adverse events
Measure	Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) n=159 participants at risk Darunavir (800 milligram \[mg\]) 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). The NRTIs (including tenofovir/emtricitabine \[Truvada\] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.	Standard of Care Postexposure Prophylaxis (SOCPEP) n=153 participants at risk Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) \[Kaletra\] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) \[Truvada\], AZT (zidovudine)/3TC (lamivudine) \[Combivir\]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual SmPCs at the discretion of either the treating physician or Investigator.
Nervous system disorders Dizziness	3.8% 6/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	1.3% 2/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Nervous system disorders Dysgeusia	0.63% 1/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	3.3% 5/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Nervous system disorders Headache	11.9% 19/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	5.2% 8/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
General disorders Asthenia	3.1% 5/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	0.65% 1/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
General disorders Fatigue	13.2% 21/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	18.3% 28/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Psychiatric disorders Sleep Disorder	0.00% 0/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	3.9% 6/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Gastrointestinal disorders Abdominal Pain Upper	8.8% 14/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	7.2% 11/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Gastrointestinal disorders Diarrhoea	28.3% 45/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	49.7% 76/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Gastrointestinal disorders Flatulence	3.1% 5/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	7.2% 11/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Gastrointestinal disorders Nausea	15.1% 24/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	26.8% 41/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Gastrointestinal disorders Vomiting	6.3% 10/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	5.9% 9/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Skin and subcutaneous tissue disorders Rash	4.4% 7/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	2.6% 4/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Metabolism and nutrition disorders Decreased Appetite	3.1% 5/159 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.	2.6% 4/153 • Up to Month 3 The safety population included all participants who received at least 1 dose of randomized HIV PEP.

Additional Information

Medical Leader, Medical Department

Janssen-Cilag GmbH

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER