Pilot Study of the Impact of Adding Raltegravir (MK-0518) to Antiretroviral Therapy in Patients With Undetectable Plasma Virus - Full Text View

Sponsors and Collaborators:	University of Pittsburgh National Cancer Institute (NCI)
Information provided by:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00618371

Purpose

The medicines used to treat HIV can suppress but cannot kill all the virus in the body. A small amount of virus remains at low levels in the part of the blood called the plasma. It is of crucial importance to identify the source of the residual virus in patients receiving antiretroviral therapy. The purpose of this study is to investigate whether the source of low level plasma virus is from latent (old) infection or ongoing (new) infection. MK-0518 is a investigational drug, which means that is not yet FDA approved, that works in a different way to other anti-HIV medicines to help kill the virus. We hypothesize that addition of MK-0518 to a stable anti-HIV regimen will reduce the viral load further in patients with undetectable plasma virus.

Condition	Intervention
HIV Infections	Drug: Raltegravir (MK-0518)

MedlinePlus related topics: AIDS

Drug Information available for: Raltegravir

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Investigating the Source of HIV-1 Viremia in Patients on Antiretroviral Therapy Through Intensification With MK-0518

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

HIV-1 RNA response: ≥ 1 log decrease in viral load [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proviral DNA response, HIV-1 sequence variation [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	October 2007
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Raltegravir 400mg PO every 12 hours for 28 days in addition to the prescribed antiretroviral therapy

Detailed Description:

This is a non-randomized, non-comparative, single center trial of antiretroviral therapy intensification using the investigational integrase inhibitor MK-0518 and an investigational viral load assay to measure response to additional antiviral therapy. Eighteen patients will receive open-label MK-0518 400 mg P.O. every 12 hours for 28 days in addition to their prescribed antiretroviral therapy. Patients will take their doses of MK-0518 without regard to food. The study will enroll patients on antiretroviral therapy regimens with CD4 counts greater than 200 cells/ul, HIV-1 RNA levels <50 copies RNA/ml plasma using a commercial assay(conventional Amplicor) and with detectable plasma virus (viral loads ≥ 1 copies RNA/ml plasma, SCA assay).

Acceptable antiretroviral regimens will include those on NRTIs + PI, NRTIs + NNRTI + PI, or NRTIs + NNRTI-containing regimens. Patients cannot have prior evidence of resistance to antiretroviral drugs. Patients will be screened for intensification by history, physical exam, and laboratory evaluations (see below). Patients who are eligible and who agree to participate will intensify their antiretroviral therapy for 28 days with MK-0518 400 mg by mouth twice a day. During the 28- day drug addition, patients will have samples drawn for SCA assay at entry and on days 7, 14, 21, and 28 (+/- 1 d), with the last day of intensification as day 28. Patients will have additional phlebotomy after intensification on days 29, 30, 35, 42, 49 and 58 (+/- 1 day). The intensification period is followed by a post- intensification period to determine whether removal of the drug resulted in viral RNA changes.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 infection documented by positive HIV-1 ELISA and positive
Male or female at least 18 years of age, and able to provide written, informed consent
Current antiretroviral therapy with DHHS-recommended regimen: NRTIs + PI, NRTIs + NNRTI + PI, or NRTIs + NNRTI
Screening CD4 > 200 cells/ µl and CD4%> 14%; does not require prophylaxis for opportunistic infections
Receiving a stable antiretroviral regimen for 4 months prior to screening
HIV-1 RNA level below the limit of detection by commercial HIV-1 RNA determination assays for at least 12 months prior to screening.
HIV RNA ≥ 0.6 copy RNA/ml plasma by SCA(single copy assay)
Hgb ≥ 9.0 mg/dl, absolute neutrophil count > 1000/mm3, platelet count > 100,000/mm3
Alkaline phosphatase, AST and ALT < 2.0 x upper limit of normal
Willing to take MK-0518 for 28 days in addition to ongoing antiretroviral therapy
Be considered clinically stable, in the opinion of the investigator, at the time of entry into the study; i.e., clinical status and all chronic medications should be unchanged for at least two weeks prior to entry.

Exclusion Criteria:

Prior participation in an MK-0518 or other integrase inhibitor trial
Requires prohibited medications noted in the protocol
Requires cytotoxic agents including hydroxyurea or vaccinations during the study period
Received immunosuppressive therapy including steroids within one month prior to treatment in this study
Used any investigational agents within a month prior to treatment in this study
Documented resistance to any drug in each of the 4 classes of licensed antiretroviral agents by genotype or phenotype
Any febrile illness (T>38oC) in the 3 weeks prior to enrollment
Any vaccination in the 6 weeks prior to enrollment
Diagnosis of acute hepatitis due to any cause
Positive Hepatitis B surface antigen
Severe renal insufficiency defined as a calculated creatinine clearance at time of screening as < 30 ml/min, based on the Cockcroft-Gault equation.
Condition (including but not limited to alcohol or other substance use) which in the opinion of the investigator would interfere with patient compliance or safety

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618371

Contacts

Contact: Deborah McMahon, MD

412-647-6710

mcmahon@dom.pitt.edu

Locations

United States, Pennsylvania
University of Pittsburgh	Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Principal Investigator: Deborah McMahon, MD
Sub-Investigator: Joseph Jones, MD
Sub-Investigator: Sharon Riddler, MD
Sub-Investigator: Emmanuel Vergis, MD

Sponsors and Collaborators

University of Pittsburgh

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Deborah McMahon, MD

University of Pittsburgh

More Information

Publications:

Natarajan V, Bosche M, Metcalf JA, Ward DJ, Lane HC, Kovacs JA. HIV-1 replication in patients with undetectable plasma virus receiving HAART. Highly active antiretroviral therapy. Lancet. 1999 Jan 9;353(9147):119-20. No abstract available.

Dornadula G, Zhang H, VanUitert B, Stern J, Livornese L Jr, Ingerman MJ, Witek J, Kedanis RJ, Natkin J, DeSimone J, Pomerantz RJ. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA. 1999 Nov 3;282(17):1627-32.

Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1605-13.

Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, Dewar RL, Planta A, Liu S, Metcalf JA, Mellors JW, Coffin JM. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 2003 Oct;41(10):4531-6.

Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, Mican J, Kovacs JA, Davey RT, Rock-Kress D, Dewar R, Liu S, Metcalf JA, Rehm C, Brun SC, Hanna GJ, Kempf DJ, Coffin JM, Mellors JW. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007 Apr;3(4):e46.

Hazuda DJ, Wolfe AL, Hastings JC, Robbins HL, Graham PL, LaFemina RL, Emini EA. Viral long terminal repeat substrate binding characteristics of the human immunodeficiency virus type 1 integrase. J Biol Chem. 1994 Feb 11;269(6):3999-4004.

Responsible Party:	University of Pittsburgh ( Deborah McMahon, MD )
Study ID Numbers:	27XS050
Study First Received:	September 29, 2007
Last Updated:	October 13, 2008
ClinicalTrials.gov Identifier:	NCT00618371 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:

Intensification
HIV viremia
Human Immunodeficiency Virus

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Viremia
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on May 07, 2009