HIV Infections
Conditions
Keywords
HIV, AIDS, raltegravir, BRAVO, protease inhibitor, treatment Experienced
Brief summary
This is a retrospective chart review of participants in raltegravir expanded access program and will compare virologic response in regimens not containing a protease inhibitor in the antiretroviral background regimen to regimens containing a protease inhibitor in the background regimen.
Detailed description
EAP charts from patients at the study sites who meet the inclusion criteria will be reviewed and data abstracted. A comparison of the response to treatment by viral load measurement with raltegravir will be compared in patients whose regimens contained a protease inhibitor (PI) with those that did not contain a PI. Other endpoints will also be assessed including percent of patients with viral loads less than 400 copies/ml, less than 50 copies/ ml, CD4 cell changes, consequences of failure of raltegravir and use of predictive parameters such as GSS and PSS.
Interventions
DRUGraltegravir
New combination ART incorporating raltegravir with other ARVs.
Sponsors
Community Research Initiative of New England
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients previously enrolled in the MK 0518 EAP are eligible * Patients not enrolled in the MK 0518 EAP (or other Raltegravir protocols) but who meet the specific EAP protocol entry criteria are eligible: * Age \>= 16 years * Limited or no treatment options due to resistance or intolerance to multiple antiretroviral regimens, documented resistance to at least one drug in each of the 3 classes of oral ARTs (NRTI, NNRTI, PI) by genotype or phenotype testing, intolerance defined as having had a clinically significant adverse event which in the opinion of the clinician provides a contraindication to the use of any drug in that class iii. Patient did not achieve virologic suppression on ART regimen prior to receipt of raltegravir iv. Patient was clinically stable at time of initiation of raltegravir, eg. clinical status and all chronic medications (except ARTs) unchanged for \>= 2 weeks prior to raltegravir receipt. * Patient received raltegravir for at least 8 weeks * Baseline and week 8 or later HIV viral load done and available for review * Resistance test (either genotypic or phenotypic test) available prior to receipt of raltegravir
Exclusion criteria
* Patient did not receive approved raltegravir dose of 400 mg BID for at least 8 weeks. * Patient chart not available for review.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Viral Load < 400 Copies /mL at Week 12. | 12 Weeks | The HIV RNA (viral load) was measured using standard of care testing via local laboratories. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Viral Load < 75 Copies/ mL at Week 12 | 12 weeks | The HIV RNA (viral load) was measured using standard of care testing via local laboratories. |
| CD4 Cell Changes Among Participants in PI vs Non-PI Group | baseline to 24 Weeks | CD4 cell counts were measured using standard of care testing via local laboratories. |
| Baseline Genotypic Sensitivity Score (GSS). The Minimal Value Was 0 and the Maximum Values Was 5.4. (0 = Minimal to no Activity in Regimen and 5.4 = High to Maximal Activity in Regimen) | Baseline | The baseline GSS is calculated by the sum of resistance scores for each drug in the regimen. For each drug in the regimen a resistance score of 0, 0.5 or 1 was assigned for high, low or no levels of resistance, respectfully. The resistance assignment was based on either the Stanford database interpretation or presence of primary IAS mutation levels of resistance. Inclusion of maraviroc or new use of enfuvirtide in the regimen was scored a 1.0. The sum of the scores of the active drugs, not including raltegravir, constituted the baseline GSS. |
| Percentage of Participants Using Etravirine in Background Regimen | Background regimen (no specific time frame) | These results report the percent of participants using Etravirine in the background regimen. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Protease Inhibitor Group Subjects who required a protease inhibitor in their new ART regimen | 254 |
| Non-protease Inhibitor Subjects who did not take a protease inhibitor in their regimen | 86 |
| Total | 340 |
Baseline characteristics
| Characteristic | Protease Inhibitor Group | Non-protease Inhibitor | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 247 Participants | 82 Participants | 329 Participants |
| Region of Enrollment United States | 254 participants | 86 participants | 340 participants |
| Sex: Female, Male Female | 25 Participants | 13 Participants | 38 Participants |
| Sex: Female, Male Male | 229 Participants | 73 Participants | 302 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Percentage of Participants With Viral Load < 400 Copies /mL at Week 12.
The HIV RNA (viral load) was measured using standard of care testing via local laboratories.
Time frame: 12 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Protease Inhibitor Group | Percentage of Participants With Viral Load < 400 Copies /mL at Week 12. | 84 Percentage of Participants |
| Non-protease Inhibitor | Percentage of Participants With Viral Load < 400 Copies /mL at Week 12. | 86 Percentage of Participants |
Secondary
Baseline Genotypic Sensitivity Score (GSS). The Minimal Value Was 0 and the Maximum Values Was 5.4. (0 = Minimal to no Activity in Regimen and 5.4 = High to Maximal Activity in Regimen)
The baseline GSS is calculated by the sum of resistance scores for each drug in the regimen. For each drug in the regimen a resistance score of 0, 0.5 or 1 was assigned for high, low or no levels of resistance, respectfully. The resistance assignment was based on either the Stanford database interpretation or presence of primary IAS mutation levels of resistance. Inclusion of maraviroc or new use of enfuvirtide in the regimen was scored a 1.0. The sum of the scores of the active drugs, not including raltegravir, constituted the baseline GSS.
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Protease Inhibitor Group | Baseline Genotypic Sensitivity Score (GSS). The Minimal Value Was 0 and the Maximum Values Was 5.4. (0 = Minimal to no Activity in Regimen and 5.4 = High to Maximal Activity in Regimen) | 1.8 score |
| Non-protease Inhibitor | Baseline Genotypic Sensitivity Score (GSS). The Minimal Value Was 0 and the Maximum Values Was 5.4. (0 = Minimal to no Activity in Regimen and 5.4 = High to Maximal Activity in Regimen) | 1.7 score |
Secondary
CD4 Cell Changes Among Participants in PI vs Non-PI Group
CD4 cell counts were measured using standard of care testing via local laboratories.
Time frame: baseline to 24 Weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Protease Inhibitor Group | CD4 Cell Changes Among Participants in PI vs Non-PI Group | -96.6 cells/mm3 |
| Non-protease Inhibitor | CD4 Cell Changes Among Participants in PI vs Non-PI Group | -134.8 cells/mm3 |
Secondary
Percentage of Participants Using Etravirine in Background Regimen
These results report the percent of participants using Etravirine in the background regimen.
Time frame: Background regimen (no specific time frame)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Protease Inhibitor Group | Percentage of Participants Using Etravirine in Background Regimen | 33 Percentage of Participants |
| Non-protease Inhibitor | Percentage of Participants Using Etravirine in Background Regimen | 58 Percentage of Participants |
Secondary
Percentage of Participants With Viral Load < 75 Copies/ mL at Week 12
The HIV RNA (viral load) was measured using standard of care testing via local laboratories.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Protease Inhibitor Group | Percentage of Participants With Viral Load < 75 Copies/ mL at Week 12 | 84 Percentage of participants |
| Non-protease Inhibitor | Percentage of Participants With Viral Load < 75 Copies/ mL at Week 12 | 86 Percentage of participants |