Effect of Addition of Raltegravir (MK-0518) to PI- or NNRTI-Based ART Regimens in HIV Infected Subjects With Undetectable Viral Load
NCT ID: NCT00515827
Last Updated: 2021-11-04
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE2
53 participants
INTERVENTIONAL
2007-11-30
2008-11-30
Brief Summary
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Detailed Description
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The study lasted 24 weeks. Participants were randomly assigned to one of two arms. Participants in Arm A were administered raltegravir in addition to their usual ART regimen from study entry until Week 12. At Week 12, subjects halted raltegravir use and received a placebo until Week 24. Participants in Arm B were administered the placebo in addition to their usual ART regimen from study entry until Week 12. At Week 12, subjects halted the placebo and received raltegravir until Week 24. A real-time polymerase chain reaction (PCR) single copy assay (SCA) capable of detecting 1 copy of HIV RNA was used to assay viral load. The cross-over design allowed assessment of the effect of intensification with raltegravir between the two arms at Weeks 10/12 and every participant enrolled in the study receiving raltegravir for 12 weeks. Primary analysis focused on weeks 10/12 measurement and with no washout period, typical analysis of cross-over design was not intended.
All participants had scheduled visits at Weeks 0, 2, 4, 10, 12, 14, 16, 22, and 24. A targeted physical exam occurred at all visits. Blood and urine collection occurred at selected visits. A medical/medication assessment occurred at trial entry. Drug dispensing and an adherence questionnaire occurred at some visits. A pregnancy test occurred at select visits. Participants' background ART medications were not provided by the study.
Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
DOUBLE
Study Groups
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Raltegravir then Placebo (Arm A)
400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12; halt raltegravir at Week 12 and add placebo twice daily for 12 weeks
Raltegravir (MK-0518)
400 mg tablet taken orally twice daily
Placebo
400 mg placebo tablet taken orally twice daily
Placebo then Raltegravir (Arm B)
Placebo administered twice daily in addition to OBR from entry until Week 12; halt placebo at Week 12 and add 400 mg raltegravir tablet twice daily for 12 weeks
Raltegravir (MK-0518)
400 mg tablet taken orally twice daily
Placebo
400 mg placebo tablet taken orally twice daily
Interventions
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Raltegravir (MK-0518)
400 mg tablet taken orally twice daily
Placebo
400 mg placebo tablet taken orally twice daily
Eligibility Criteria
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Inclusion Criteria
* ART for at least 12 months prior to study entry that includes at least two NRTIs and either an NNRTI or a ritonavir-boosted PI
* No change in ART regimen for at least 3 months prior to study entry
* CD4 count of 200 or more at screening
* Viral load below the limit of quantification of an ultrasensitive assay for at least 6 months prior to study entry
* Viral load less than 50 copies/ml using Roche Amplicor HIV-1 RNA Ultrasensitive assay within 60 days of study entry
* All viral load assays obtained within 6 months prior to study entry lower than limits of quantification on all tests
* Pre-ART viral load level greater than 100,000 copies/ml
* Detectable viral load of 1 copy or more on the screening SCA
* Available pre-study entry plasma sample for SCA viral load determination
* Absolute neutrophil count of 750/mm3 or more
* Hemoglobin of 9 g/dL or more for female subjects and 10 g/dL or more for male subjects
* Platelet count of 50,000/mm3 or more
* Calculated creatinine clearance of 30 ml/min or more
* AST, ALT, and alkaline phosphate less than or equal to 5 x ULN
* Total bilirubin less than or equal to 2.5 x ULN. If subject is taking indinavir or atazanavir at screening, total bilirubin must be less than or equal to 5 x ULN.
* Negative serum or urine pregnancy test within 48 hours prior to study entry for females with reproductive potential
* Willing to use acceptable means of contraception
Exclusion Criteria
* Unstable clinical condition that would preclude the subject from undergoing study procedures
* Use of immunosuppressive medications within 60 days prior to study entry. Participants using inhaled or nasal steroids are not excluded.
* Opportunistic infection within 60 days prior to study entry
* Allergy or sensitivity to components of study drug
* Active drug or alcohol abuse
* Serious illness requiring systemic treatment within 60 days prior to study entry
* Receipt of non-HIV vaccination within 30 days prior to study entry
* Receipt of any HIV vaccines
* Plan to change background ART within 24 weeks after study entry
* Pregnant or breastfeeding
18 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Rajesh T Gandhi, MD
Role: STUDY_CHAIR
Massachusetts General Hospital
Joseph J Eron Jr., MD
Role: STUDY_CHAIR
University of North Carolina, Chapel Hill
John W Mellors, MD
Role: STUDY_CHAIR
University of Pittsburgh Medical Center
Locations
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Alabama Therapeutics CRS
Birmingham, Alabama, United States
Stanford CRS
Palo Alto, California, United States
Ucsf Aids Crs
San Francisco, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Northwestern University CRS
Chicago, Illinois, United States
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States
Washington U CRS
St Louis, Missouri, United States
Cornell CRS
New York, New York, United States
NY Univ. HIV/AIDS CRS
New York, New York, United States
Columbia P&S CRS
New York, New York, United States
Harlem ACTG CRS
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Unc Aids Crs
Chapel Hill, North Carolina, United States
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States
MetroHealth CRS
Cleveland, Ohio, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States
Pitt CRS
Pittsburgh, Pennsylvania, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Countries
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References
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Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD; Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007 Apr 14;369(9569):1261-1269. doi: 10.1016/S0140-6736(07)60597-2.
Kassahun K, McIntosh I, Cui D, Hreniuk D, Merschman S, Lasseter K, Azrolan N, Iwamoto M, Wagner JA, Wenning LA. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos. 2007 Sep;35(9):1657-63. doi: 10.1124/dmd.107.016196. Epub 2007 Jun 25.
Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. doi: 10.1097/QAI.0b013e31802b4956.
Gandhi RT, Zheng L, Bosch RJ, Chan ES, Margolis DM, Read S, Kallungal B, Palmer S, Medvik K, Lederman MM, Alatrakchi N, Jacobson JM, Wiegand A, Kearney M, Coffin JM, Mellors JW, Eron JJ; AIDS Clinical Trials Group A5244 team. The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med. 2010 Aug 10;7(8):e1000321. doi: 10.1371/journal.pmed.1000321.
Gandhi RT, Coombs RW, Chan ES, Bosch RJ, Zheng L, Margolis DM, Read S, Kallungal B, Chang M, Goecker EA, Wiegand A, Kearney M, Jacobson JM, D'Aquila R, Lederman MM, Mellors JW, Eron JJ; AIDS Clinical Trials Group (ACTG) A5244 Team. No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy. J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):229-35. doi: 10.1097/QAI.0b013e31823fd1f2.
Other Identifiers
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10440
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG A5244
Identifier Type: -
Identifier Source: secondary_id
A5244
Identifier Type: -
Identifier Source: org_study_id