Human Immunodeficiency Virus (HIV)
Conditions
Keywords
Human Immunodeficiency Virus (HIV) Post exposure prophylaxis, DRV/r, Occupational injury, Non-occupational exposure, Prezista, Darunavir/r
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.
Interventions
Darunavir (DRV) type=exact number, unit=mg, number=800, form=tablet, route=oral use. Tablet is taken once a day, for 28 days; Ritonavir (r) type=exact number, unit=mg, number=100, form=tablet, route=oral use. Tablet is taken once a day, for at least 28 days and a maximum of 30 days.
DRUGLopinavir in fixed combination with Ritonavir
type=exact number, unit=mg, number=400/100, form=tablet, route=oral use. Tablet is taken once or twice a day, for at least 28 days and a maximum of 30 days.
DRUGZidovudine
type=exact number, unit=mg, number=250, form=tablet, route=oral use. Tablet is taken twice a day, for at least 28 days and a maximum of 30 days.
DRUGNRTIs
The NRTIs (including tenofovir/emtricitabine \[Truvada\], lamivudine/zidovudine \[Combivir\]) will be administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
DRUGEfavirenz
type=exact number, unit=mg, number=600, form=tablet, route=oral use. Tablet is taken once a day, for at least 28 days and a maximum of 30 days.
Sponsors
Janssen-Cilag G.m.b.H
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 159 |
| 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. | 153 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 |
| Overall Study | Lost to Follow-up | 7 | 8 |
| Overall Study | Other | 9 | 7 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) | Standard of Care Postexposure Prophylaxis (SOCPEP) | Total |
|---|---|---|---|
| Age, Continuous | 34.2 years STANDARD_DEVIATION 9.2 | 32.3 years STANDARD_DEVIATION 9.3 | 33.3 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 28 Participants | 28 Participants | 56 Participants |
| Sex: Female, Male Male | 131 Participants | 125 Participants | 256 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 96 / 159 | 111 / 153 |
| serious Total, serious adverse events | 1 / 159 | 0 / 153 |
Outcome results
Primary
Number of Participants With Early Discontinuation From Randomized Human Immunodeficiency Virus Postexposure Prophylaxis (HIV PEP)
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.
Time frame: Up to 30 days
Population: Analysis was performed on PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) | Number of Participants With Early Discontinuation From Randomized Human Immunodeficiency Virus Postexposure Prophylaxis (HIV PEP) | 10 participants |
| Standard of Care Postexposure Prophylaxis (SOCPEP) | Number of Participants With Early Discontinuation From Randomized Human Immunodeficiency Virus Postexposure Prophylaxis (HIV PEP) | 15 participants |
p-value: 0.2434Cochran-Mantel-Haenszel
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Time frame: Up to Month 3
Population: The safety population included all participants who received at least 1 dose of randomized HIV PEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 131 participants |
| Standard of Care Postexposure Prophylaxis (SOCPEP) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 125 participants |
p-value: 0.8839Fisher Exact
Secondary
Percentage of Participants Who Developed Detectable HIV Antibodies
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) | Percentage of Participants Who Developed Detectable HIV Antibodies | Negative | 99.3 percentage of participants |
| Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) | Percentage of Participants Who Developed Detectable HIV Antibodies | Positive | 0.7 percentage of participants |
| Standard of Care Postexposure Prophylaxis (SOCPEP) | Percentage of Participants Who Developed Detectable HIV Antibodies | Negative | 100 percentage of participants |
| Standard of Care Postexposure Prophylaxis (SOCPEP) | Percentage of Participants Who Developed Detectable HIV Antibodies | Positive | 0 percentage of participants |
Secondary
Worst Sheehan Disability Scale (SDS) Score for the Safety Population
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).
Time frame: Month 3
Population: The safety population included all participants who received at least 1 dose of randomized HIV PEP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) | Worst Sheehan Disability Scale (SDS) Score for the Safety Population | Impairment in social life | 2.465 units on a scale | Standard Deviation 2.594 |
| Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) | 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 |
| Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) | Worst Sheehan Disability Scale (SDS) Score for the Safety Population | Impairment in family life | 2.226 units on a scale | Standard Deviation 2.624 |
| Standard of Care Postexposure Prophylaxis (SOCPEP) | Worst Sheehan Disability Scale (SDS) Score for the Safety Population | Impairment in work/school/studies | 3.503 units on a scale | Standard Deviation 2.94 |
| Standard of Care Postexposure Prophylaxis (SOCPEP) | Worst Sheehan Disability Scale (SDS) Score for the Safety Population | Impairment in social life | 3.464 units on a scale | Standard Deviation 2.786 |
| Standard of Care Postexposure Prophylaxis (SOCPEP) | Worst Sheehan Disability Scale (SDS) Score for the Safety Population | Impairment in family life | 2.954 units on a scale | Standard Deviation 2.713 |