BRAVO: Background Regimen of Raltegravir on Virologic Outcome (BRAVO)

Outcomes of Early Raltegravir Experience: Comparison of Virologic Response in Regimens Not Containing a Protease Inhibitor in the Antiretroviral Background Regimen Versus a Protease Inhibitor in the Background Regimen

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: raltegravir

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.

• Study Type: Observational
• Enrollment (Actual): 442

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90028
      • AIDS Healthcare Foundation
    • Los Angeles, California, United States, 900036
      • Light Source Medical
    • Los Angeles, California, United States, 90036
      • Synergy Hematology and Oncology
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Connecticut
    • Glastonbury, Connecticut, United States, 06033
      • Connecticut Health Care Group
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20009
      • Dupont Circle Physicians Group
    • Washington, D.C., District of Columbia, United States, 20036
      • Capital Medical Associates PC
  • Florida
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Ruth M. Rothstein CORE Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Community Research Initiative
    • Springfield, Massachusetts, United States, 01107
      • Community Research Initiative - West
  • New York
    • Buffalo, New York, United States, 14215
      • Infectious Diseases and HIV Medicine Immunodeficiency Clinic
    • New York, New York, United States, 10003
      • Bellman, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mounzer, MD
  • Texas
    • Dallas, Texas, United States, 75204
      • Dr. Nicholaos C. Bellos & Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of individuals who were previously enrolled in raltegravir expanded access program(EAP) and completed at least 8 weeks of treatment with raltegravir, whose chart from EAP program is available for review, and whose resistance testing prior to initiation of raltegravir is available.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Protease Inhibitor Group; Subjects who required a protease inhibitor in their new ART regimen	Drug: raltegravir; New combination ART incorporating raltegravir with other ARVs.
Non-protease Inhibitor; Subjects who did not take a protease inhibitor in their regimen	Drug: raltegravir; New combination ART incorporating raltegravir with other ARVs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks
CD4 Cell Changes Among Participants in PI vs Non-PI Group	CD4 cell counts were measured using standard of care testing via local laboratories.	baseline to 24 Weeks
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.	Baseline
Percentage of Participants Using Etravirine in Background Regimen	These results report the percent of participants using Etravirine in the background regimen.	Background regimen (no specific time frame)

Collaborators and Investigators

• Sponsor: Community Research Initiative of New England
• Investigators: Principal Investigator: Daniel Skiest, MD, Community Research Initiative

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2008
• Primary Completion (Actual): June 15, 2009
• Study Completion (Actual): June 15, 2009

Study Registration Dates

• First Submitted: September 11, 2008
• First Submitted That Met QC Criteria: September 11, 2008
• First Posted (Estimate): September 12, 2008

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: HIV; AIDS; raltegravir; protease inhibitor; treatment Experienced; BRAVO
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: 07-11