Pilot Study of Adding Raltegravir (MK-0518) to Antiretroviral Therapy in Patients With Low Level Viremia

NCT00618371 | Completed Results DMC

• 3 other identifiers: 27XS050HHSN261200800001EZIABC011464
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infection

Keywords

Intensification; HIV viremia; Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (1)

• Number of Participants With HIV-1 RNA Response: ≥ 1 Log Decrease in Viral Load

  HIV RNA levels were determined with a non-commercial, sensitive single copy assay for HIV. The primary outcome measure was to determine the number of individuals with ≥10fold decrease in HIV RNA

  4 weeks

Secondary Outcomes (1)

• Proviral DNA Response, HIV-1 Sequence Variation Levels of Cell Associated HIV DNA and Genetic Variation in HIV During Raltegravir Addition in Individuals Who Have Declines in HIV

  4 weeks

Study Arms (1)

Raltegravir intensification

EXPERIMENTAL

Patients will be administered raltegravir 400 mg orally twice daily in addition to antiretroviral therapy

Drug: Raltegravir (MK-0518)

Interventions

Raltegravir (MK-0518) DRUG

Antiretroviral drug intensification with Raltegravir (MK0518) 400mg orally every 12 hours for 28 days in addition to the prescribed antiretroviral therapy

Also known as: MK-0518

Raltegravir intensification

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Department of Health and Human Services (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, Aspartate transaminase (AST) and Alanine aminotransferase (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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (7)

• 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. doi: 10.1016/s0140-6736(05)76156-0. No abstract available.

  PMID: 10023903 BACKGROUND

• 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. doi: 10.1001/jama.282.17.1627.

  PMID: 10553788 BACKGROUND

• 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. doi: 10.1056/NEJM199905273402101.

  PMID: 10341272 BACKGROUND

• 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. doi: 10.1128/JCM.41.10.4531-4536.2003.

  PMID: 14532178 BACKGROUND

• 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. doi: 10.1371/journal.ppat.0030046.

  PMID: 17411338 BACKGROUND

• 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.

  PMID: 8307956 BACKGROUND

• McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, Palmer S, McNulty S, Metcalf JA, Acosta E, Rehm C, Coffin JM, Mellors JW, Maldarelli F. Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clin Infect Dis. 2010 Mar 15;50(6):912-9. doi: 10.1086/650749.

  PMID: 20156060 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Deborah McMahon
• Organization: University of Pittsburgh

mcmahond@pitt.edu

412-383-1675

Study Officials

• Deborah McMahon, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 29, 2007
• First Posted: February 20, 2008
• Study Start: October 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: February 1, 2017
• Results First Posted: December 6, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)