Raltegravir Added to Stable HAART in HIV-1 Infected Subjects With Viral Suppression and Low CD4 Recovery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00562510
Recruitment Status : Terminated (recruitment lower than estimated)
First Posted : November 22, 2007
Last Update Posted : June 9, 2015
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Pedro Cahn, The Huesped Foundation

Brief Summary:

This is a Phase 3, randomized, double blinded, placebo-controlled study designed to compare the safety, tolerability, antiviral activity and immunological effect of raltegravir added to a previously stable HAART regimen in the treatment of HIV-1 infected subjects with undetectable viraemia and low CD4 recovery.


Adding raltegravir to a stable HAART in patients with undetectable plasma viral load and low CD4 recovery will result in further viral suppression and therefore higher CD4 recovery.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Raltegravir Drug: Placebo Phase 3

Detailed Description:

Although HAART has reduced the morbidity and mortality from HIV-1 infection, some patients experience a discordant response characterized by HIV-1 RNA plasma levels below the limit of detection and low CD4 T-cell recovery (immunologic discordant responders). At present, recommendations for the clinical management of patients with discordant responses to antiretroviral therapy are largely based on observational, uncontrolled data.

The effect on CD4 count of adding raltegravir in already undetectable patients has not yet been evaluated.

The primary purpose of this study is to assess the ability of the HIV-1 integrase inhibitor, raltegravir, added to a stable HAART, to increase CD4 count in patients with undetectable plasma viral load and low CD4 recovery.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double Blinded, Placebo Controlled Study of Raltegravir Added to Stable HAART in HIV-1 Infected Subjects With Viral Suppression and Low CD4 Recovery
Study Start Date : August 2008
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Raltegravir Drug: Raltegravir
Raltegravir 400 mg BID added to stable HAART

Placebo Comparator: Raltegravir matching placebo Drug: Placebo
Placebo BID added to stable HAART

Primary Outcome Measures :
  1. Proportion of subjects increasing CD4 count > 50 cells/mm³. [ Time Frame: 48 weeks ]

Secondary Outcome Measures :
  1. Proportion of patients achieving plasma HIV-RNA < 5 copies/ml. [ Time Frame: 48 weeks ]
  2. Proportion of subjects increasing CD4 count > 50 cells/mm³. [ Time Frame: 24 weeks ]
  3. Proportion of patients achieving CD4 count > 250 cells/mm3 [ Time Frame: 48 weeks ]
  4. Proportion of patients achieving an increase of 5 percentual points in CD4 percentage [ Time Frame: 48 weeks ]
  5. Median change from baseline in CD4 count. [ Time Frame: 48 weeks ]
  6. Proportion of patients maintaining HIV RNA <50 copies/ml. [ Time Frame: 48 weeks ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Documented HIV-1 infection.
  • Subject has voluntarily signed and dated an informed consent form.
  • Documented sustained HIV RNA < 50 copies/ml (two consecutive pVL < 50 copies/ml, first VL > 12 months before the screening date) without documentation of HIV RNA > 50 copies/ml for at least 12 months while on previous stable HAART (PS_HAART).
  • HIV RNA < 50 copies/ml at screening.
  • Subject is currently receiving an antiretroviral regimen which has not changed for at least 12 months.
  • CD4 count < 200 cells/ mm3 AND CD4 increase < 100 cells/ mm3 in the last 12 months.
  • Subject's vital signs, physical examination and laboratory results do not exhibit evidence of acute illness.
  • Negative serum or urine pregnancy test and willing to use acceptable means of contraception.

Exclusion Criteria:

  • Patient is receiving tenofovir DF AND didanosine as a component of the background antiretroviral therapy.
  • Patient has a current (active) diagnosis of acute hepatitis due to any cause OR chronic hepatitis B and/or C WITH aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)>2.5 x upper limit of normal (ULN) AND/OR is likely to require treatment in the next year.
  • Subject has significant history of cardiac, renal, neurologic, psychiatric, oncologic, metabolic, or hepatic disease or any condition that, in the investigators opinion, could compromise the subject's safety or adherence to the trial protocol.
  • Subject has a currently active AIDS defining illness (category C conditions according to the CDC Classification System for HIV infection 1993) within 30 days of screening. Subjects who are on stable maintenance therapy for an opportunistic infection may be enrolled.
  • Life expectancy < 1 year according to the judgment of the investigator.
  • Screening laboratory analysis show any of the following abnormal laboratory results:

    • Hemoglobin < 8.0 g/dL
    • Absolute neutrophil count < 750 cells/µL
    • Platelet count < 50,000 mm3
  • Use of any investigational agents within 30 days prior to screening.
  • Previous use of integrase inhibitors.
  • Use of immunosuppressive drugs, cytokine inhibitors or other cytokines in the last year.
  • Continuous use of systemic corticoids for more than a month in the last year or any use in the last 3 months.
  • Subject has an ongoing history of substance abuse or psychiatric illness.
  • Subject is pregnant or breast-feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00562510

Fundacion Huesped
Buenos Aires, Argentina, 1202
Sponsors and Collaborators
Pedro Cahn
Merck Sharp & Dohme Corp.
Principal Investigator: Pedro E Cahn, MD, PhD Fundacion Huesped

Additional Information:
Responsible Party: Pedro Cahn, MD, The Huesped Foundation Identifier: NCT00562510     History of Changes
Other Study ID Numbers: FH-RAL-01
First Posted: November 22, 2007    Key Record Dates
Last Update Posted: June 9, 2015
Last Verified: June 2015

Keywords provided by Pedro Cahn, The Huesped Foundation:
HIV-1 infection
immune discordance
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action