HIV, Virus Diseases
Conditions
Keywords
Safety
Brief summary
The purpose of this study is to determine whether raltegravir 400 mg b.i.d. in a boosted PI regimen is as efficacious and safe as the NRTI backbone in a boosted PI regimen.
Interventions
DRUGSwitch NRTIs as a Backbone to Raltegravir
This is a multicenter, pilot randomized, controlled study to evaluate the safety and efficacy of raltegravir in patients switched from a stable boosted PI-based regimen with a NRTI backbone to raltegravir instead of their current NRTIs. A stable boosted PI-based regimen is defined as having a documented HIV RNA \<75 copies/mL for ≥ 3 months prior to study entry, while receiving a boosted PI-based with NRTI backbone. Additionally, patients must not have had HIV RNA ≥ 75 copies/mL during the three months prior to study entry. Approximately 25 patients will be enrolled in the raltegravir treatment arm (Group 1) and approximately 25 patients in the continuation of the current NRTI backbone regimen treatment arm (Group 2). Patients will be randomly assigned 1:1 to a treatment group.
Sponsors
Merck Sharp & Dohme LLC
St. Joseph's Hospital, Florida
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patient is a male or female at least 18 years of age on the day of signing the informed consent. 2. Patient is HIV positive as determined by enzyme-linked immunosorbent assay (ELISA) or HIV PCR. 3. Patient has documented HIV RNA \<75 copies/mL for at least 3 months prior to study entry while on a stable boosted PI based regimen without a change in antiretroviral therapy and with no documentation of HIV RNA \> or = 75 copies/mL during this time. 4. Patient has no history of documented coronary artery disease that clinical investigator deems as clinically significant. 5. Patient has the following laboratory values within 35 days prior to the treatment phase of this study: * Alkaline phosphatase ≤ 5.0 x upper limit of normal * AST (SGOT) and ALT (SGPT) ≤ 5.0 x upper limit of normal. Patients with Hepatitis C Coinfection may be enrolled provided the patients are stable and meet all eligibility criteria. 6. Patient has no clinical evidence of active pulmonary disease; at the investigators, discretion a chest x-ray could be obtained if felt necessary. 7. Patient who is of reproductive potential agrees to use an acceptable method of birth control throughout the study. 8. Patient agrees to remain off prohibited concomitant medications as outlined in Section 3.2.1 of the protocol.
Exclusion criteria
1. Patients who are currently failing a boosted PI based regimen. 2. Patient is receiving a second line boosted PI regimen including boosted tripranavir or boosted darunavir. 3. Patients with chronic hepatitis B infection. 4. Patient has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate. 5. Patient has a history of alcohol or other substance abuse that in the opinion of the investigator would interfere with patient compliance or safety. 6. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent. 7. Patient has ever used any experimental HIV-integrase inhibitor. 8. Patient has used systemic immunosuppressive therapy (e.g., 20 mg or more of prednisone or equivalent per day) within one month prior to treatment in this study. Short courses of corticosteroids (e.g., as for asthma exacerbation) will be allowed. 9. Patient requires hemodialysis. 10. Patient has significant hypersensitivity or other contraindication to any of the components of the study drugs. 11. Patient has chronic hepatitis, including chronic hepatitis B and/or C and has decompensated liver disease. 12. Patient is pregnant or breastfeeding, or expecting to conceive (within the duration of the study). Patient is expecting to donate eggs (within the duration of the study). Patient is expecting to donate sperm (within the duration of the study). 13. Subjects who have received investigational medications within 30 days of baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Suppressed Viral Load(<75 Copies/ml)in Raltegravir 400 mg Bid vs. NRTI Backbone, Each in Combination of Boosted PI Regimen | at 24weeks for each patient | Number of patients with virologic suppression\< 75 copies/ ml at 24 wk,in raltegravir 400 mg bid vs. NRTI backbone, each in combination of boosted PI regimen. |
Secondary
| Measure | Time frame |
|---|---|
| Virologic Suppression of < 75 Copies/ml at 48 Weeks | at 48 weeks for each patient |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the HIllsborough County Health Department, and Tampa Care Clinic, Tampa, Florida.
Pre-assignment details
Per the inclusion and exclusion criteria
Participants by arm
| Arm | Count |
|---|---|
| 1: Boosted PI+RAL Group 1 Raltegravir 400 mg PO b.i.d. + their current boosted PI regimen | 21 |
| 2: Boosted PI+NRTIs Group 2 Continue the same regimen without change | 25 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 8 |
Baseline characteristics
| Characteristic | 2: Boosted PI+NRTIs | 1: Boosted PI+RAL | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 21 Participants | 46 Participants |
| Age, Continuous | 49 years STANDARD_DEVIATION 8 | 45 years STANDARD_DEVIATION 9 | 47 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 25 participants | 21 participants | 46 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 19 Participants | 15 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 21 | 18 / 25 |
| serious Total, serious adverse events | 0 / 21 | 1 / 25 |
Outcome results
Primary
Number of Patients With Suppressed Viral Load(<75 Copies/ml)in Raltegravir 400 mg Bid vs. NRTI Backbone, Each in Combination of Boosted PI Regimen
Number of patients with virologic suppression\< 75 copies/ ml at 24 wk,in raltegravir 400 mg bid vs. NRTI backbone, each in combination of boosted PI regimen.
Time frame: at 24weeks for each patient
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boosted PI+RAL | Number of Patients With Suppressed Viral Load(<75 Copies/ml)in Raltegravir 400 mg Bid vs. NRTI Backbone, Each in Combination of Boosted PI Regimen | 18 participants |
| Boosted PI+NRTIs | Number of Patients With Suppressed Viral Load(<75 Copies/ml)in Raltegravir 400 mg Bid vs. NRTI Backbone, Each in Combination of Boosted PI Regimen | 18 participants |
p-value: 0.935Fisher Exact
Secondary
Virologic Suppression of < 75 Copies/ml at 48 Weeks
Time frame: at 48 weeks for each patient
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boosted PI+RAL | Virologic Suppression of < 75 Copies/ml at 48 Weeks | 14 participants |
| Boosted PI+NRTIs | Virologic Suppression of < 75 Copies/ml at 48 Weeks | 16 participants |