The purpose of this study is to determine whether the HIV vaccine MRKAd5 HIV-1 gag/pol/nef followed by treatment interruption can increase immune system function in adults with acute or recent HIV infection who have started taking anti-HIV drugs.

Condition	Intervention	Phase
HIV Infections	Vaccine: MRKAd5 HIV-1 gag/pol/nef	Phase II

Further Study Details: 

Primary Outcomes: Average of log10 HIV-1 RNA viral load at Weeks 58 and 63; frequency of Grade 3 or 4 systemic adverse events, the occurrence of a severe or life-threatening injection site adverse event, or death from time of vaccination until Week 63
Secondary Outcomes: Median plasma HIV RNA viral load at Weeks 63 and 87; proportion of patients with controlled viremia and their respective median plasma HIV RNA viral load at Weeks 63 and 87; mean viral burden, defined as time-averaged area under the log10 HIV-1 RNA viral load curve at Weeks 63 and 87; HIV DNA levels at Weeks 30, 38, 63, and 87; HIV-1 DNA levels at Weeks 30, 38, 46, 50, 63, and 87; magnitude and absolute change in CD4 and CD8 counts at Weeks 63 and 87; percent and absolute change in the number of HIV-1 specific CD8 cells, as measured by interferon (IFN)-gamma Elispot assay and intracellular cytokine staining, from baseline to Week 30; percent and absolute change in the cytokine secretion patterns and the proliferative capacity of HIV-1 specific CD4 and CD8 cells, as measured by multiparameter flow cytometry from baseline to Week 30; breadth and magnitude of HIV-1 specific CD4 and CD8 cell responses at Week 38 and time to reaching the specified virologic or immunologic criteria for reinitiating antiretroviral therapy after treatment interruption; time to reach the specified virologic or immunologic criteria for reinitiating antiretroviral therapy after treatment interruption; frequency of Grade 3 or 4 systemic adverse events or the occurrence of a severe or life-threatening injection site adverse event until Week 240, or HIV-related events, AIDS-defining infections, and death from time of vaccination until Week 87; cell-associated infectivity in latently infected cells at Week 63; cell-associated infectivity at Week 63 and immunologic responses at Weeks 63 and 87
Expected Total Enrollment:  120

While the advent of highly active antiretroviral therapy (HAART) has contributed to the increasing control of HIV infection and viral replication, ultimate control of HIV infection will require the development of effective HIV-specific immunity in HIV infected individuals. Therapeutic vaccination within the earliest weeks following acute or recent HIV infection may increase the immune system''''s response to HIV. This study will determine whether MRKAd5 HIV-1 gag/pol/nef vaccine followed by treatment interruption can maintain viral suppression in patients with acute or recent HIV infection.

The interventional part of the study will last 102 weeks. Participants will be randomly assigned to receive either MRKAd5 HIV-1 gag/pol/nef or placebo vaccine at baseline and Weeks 4 and 26. Participants must remain on HAART from study entry until Week 38. Participants whose HIV viral load rebounds two times or more above 500 copies/ml by Week 39 will not enter Step 2 of the study. Participants whose viral load drops to 500 copies/ml or less by Week 39 will enter Step 2, where they will discontinue HAART for 24 weeks. Study participants will continue in Step 2 until they experience virologic and immunologic failure; they will then enter Step 3, where they will reinitiate HAART. Step 3 participants will continue on HAART until Week 102. A long-term safety follow-up period will occur from Weeks 103 to 240.

Timing of the study visits will be determined by which steps a participant enters. A physical exam and blood and urine collection will occur at most study visits throughout the study until Week 102. Follow-up phone calls to study participants will occur every 6 months from Week 102 until Week 240 to collect long-term safety data, including clinical status, CD4 count, and medication history. During the long-term safety follow-up, participants will also have study visits every 6 months. Visits will include medical and medication history.

Ages Eligible for Study:  18 Years   -   55 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Initiated HAART within 16 days of an acute or recent HIV-1 infection diagnosis. More information on this criterion can be found in the protocol.
• Initiated HAART within 16 days of documented acute or recent HIV-1 infection without interruption for more than 7 days
• Sustained viral suppression, defined as a viral load of 500 copies/mL or less 6 months prior to baseline with an undetectable HIV-1 RNA viral load at screening
• CD4 count of 450 cells/mm3 or more OR 35% or more between 45 to 14 days prior to screening
• Ad5 neutralizing antibody titer of 200 or less at screening
• Willing to follow all study procedures and schedules
• Willing to interrupt HAART for at least 24 weeks following completion of the vaccination stage
• Negative for hepatitis B surface antigen (HBsAg) at screening
• Willing to use acceptable methods of contraception
• Infected with HIV-1 subtype B, if this information is available

Exclusion Criteria:

• Virologic relapse, defined as 2 consecutive measurements of viral load of 500 copies/mL or more at least 7 days apart 6 months prior to baseline
• Received more than 7 days of continuous HAART other than that received within 16 days of acute or recent HIV-1 infection. Participants who received HAART as part of post-exposure prophylaxis (PEP) more than 6 months prior to the start of initial HAART may be eligible, provided that they did not acquire HIV-1 infection from the event that required PEP.
• History of anaphylaxis or allergy to vaccine components, including Tris buffer, magnesium chloride, and polysorbate 80 (Tween)
• History of clinically significant heart, lung, kidney, liver, pancreatic, gastrointestinal, or neurological disease that, in the opinion of the study investigator, may interfere with the study
• Contraindication to intramuscular (IM) injection, such as anticoagulant therapy or thrombocytopenia
• Receipt of any immune globulin or blood products within 3 months prior to baseline
• Receipt of any live vaccine within 30 days prior to baseline or any inactivated vaccine within 14 days prior to baseline
• Previous receipt of any HIV vaccine. Participants that were documented to have received only placebo are not excluded.
• History of any AIDS-defining illness. If a participant''''s sole AIDS-defining illness is Kaposi''''s sarcoma limited to the skin and is not anticipated to require systemic chemotherapy, that participant is not excluded.
• Currently receiving drugs or biologics not approved by the Food and Drug Administration (FDA) other than investigational HIV medications
• Use of any immunomodulatory agents, including but not limited to interleukin-2 (IL-2), granulocyte/macrophage-colony stimulating factor (GM-CSF), and systemic corticosteroids, within 30 days prior to baseline
• Active alcohol or substance use that, in the investigator''''s opinion, may interfere with the study
• Any other criteria or condition that, in the investigator''''s opinion, may interfere with the study
• Unwilling or unable to contribute to the planned peripheral blood mononuclear cell (PBMC) blood collection
• Pregnancy or breastfeeding

Please refer to this study by ClinicalTrials.gov identifier  NCT00183261

Study chairs or principal investigators

Susan Little, MD,  Study Chair,  University of California, San Diego AIDS Vaccine Research Center   
Douglas D. Richman, MD,  Study Chair,  Departments of Pathology and Medicine, University of California, San Diego   

Study ID Numbers:  AIN504-A5218
Last Updated:  September 15, 2005
Record first received:  September 13, 2005
ClinicalTrials.gov Identifier:  NCT00183261
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-20