Immune Response to a Therapeutic HIV Vaccine Followed by Treatment Interruption in Patients With Acute or Recent HIV Infection

HIV Infections Clinical Trial

Official title:

A Randomized Phase II Study of Therapeutic Immunization and Treatment Interruption Among Subjects Who Began Potent Antiretroviral Therapy Within 30 Days of Diagnosis of Acute or Recent HIV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00183261
• Other study ID #: AIN504/A5218
• Secondary ID: 10025AIN504/ACTG
• Status: Completed
• Phase: Phase 2
• Start date: March 2006
• Est. completion date: October 2010

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 Weeks 39 to 41 will not enter Step 2 of the study. Participants whose viral load drops to 500 copies/ml or less by Weeks 39 to 41 will enter Step 2, where they will discontinue HAART for 24 weeks. Participants in Step 2 will have plasma HIV viral loads measured every 2 weeks for the first 4 weeks and weekly for the next 3 weeks. Study participants will continue in Step 2 until they experience virologic and immunologic failure or they need to restart HAART for another reason; 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: October 2010
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Initiated HAART within 30 days of an acute or recent HIV-1 infection diagnosis. More information on this criterion can be found in the protocol.

• Initiated HAART within 30 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 12 months prior to baseline with an undetectable HIV-1 RNA viral load between 60 to 7 days prior to baseline

• CD4 count of 450 cells/mm3 or more OR 35% or more between 60 to 14 days prior to baseline

• 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 forms 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 within 12 months of baseline visit

• 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

• Current or past participation in other studies that might alter the participant's response to the study vaccination

• 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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections

Intervention

Biological:
• MRKAd5 HIV-1 gag/pol/nef
1.5 x 1010 Ad vg/mL, 1.0 mL administered intramuscularly
• MRKAd5 HIV-1 gag/pol/nef placebo
1.0 mL administered intramuscularly

Locations

Country	Name	City	State
American Samoa	407 Doctors CRS	Surry Hills
Australia	AIDS Research Initiative, Darlinghurst CRS	Darlinghurst	New South Wales
Australia	Holdsworth House Medical Practice CRS	Darlinghurst	New South Wales
Australia	St. Vincent's Hospital CRS	Darlinghurst	New South Wales
Australia	Taylor Square Private Clinic CRS	Darlinghurst	New South Wales
Australia	407 Doctors (Australia) AIEDRP	Sydney
Australia	AIDS Research Initiative (Australia) AIEDRP	Sydney
Australia	Holdsworth House Gen. Practice (Australia) AIEDRP	Sydney
Australia	St. Vincent's Hosp. (Australia) AIEDRP	Sydney
Australia	Taylor Square Private Clinic (Australia) AIEDRP	Sydney
United States	Fenway Community Health Ctr. CRS	Boston	Massachusetts
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	UNC, Chapel Hill AIEDRP	Chapel Hill	North Carolina
United States	Univ. of Colorado Health Sciences Ctr. AIEDRP	Denver	Colorado
United States	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina
United States	Dumc Aiedrp	Durham	North Carolina
United States	Aaron Diamond AIDS Research Ctr. AIEDRP	New York	New York
United States	Beth Israel Med. Ctr., ACTU	New York	New York
United States	The Miriam Hosp. ACTG CRS	Providence	Rhode Island
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsd Aiedrp	San Diego	California
United States	Ucsf Aiedrp	San Francisco	California
United States	LA Biomedical Research Institute at Harbor-UCLA AIEDRP	Torrance	California

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Acute Infection and Early Disease Research Program, AIDS Clinical Trials Group

Countries where clinical trial is conducted

United States,  American Samoa,  Australia, 

References & Publications (4)

Markowitz M, Jin X, Hurley A, Simon V, Ramratnam B, Louie M, Deschenes GR, Ramanathan M Jr, Barsoum S, Vanderhoeven J, He T, Chung C, Murray J, Perelson AS, Zhang L, Ho DD. Discontinuation of antiretroviral therapy commenced early during the course of human immunodeficiency virus type 1 infection, with or without adjunctive vaccination. J Infect Dis. 2002 Sep 1;186(5):634-43. Epub 2002 Aug 9. — View Citation

Moss RB, Brandt C, Giermakowska WK, Savary JR, Theofan G, Zanetti M, Carlo DJ, Wallace MR. HIV-specific immunity during structured antiviral drug treatment interruption. Vaccine. 2003 Mar 7;21(11-12):1066-71. — View Citation

Papasavvas E, Ortiz GM, Gross R, Sun J, Moore EC, Heymann JJ, Moonis M, Sandberg JK, Drohan LA, Gallagher B, Shull J, Nixon DF, Kostman JR, Montaner LJ. Enhancement of human immunodeficiency virus type 1-specific CD4 and CD8 T cell responses in chronically infected persons after temporary treatment interruption. J Infect Dis. 2000 Sep;182(3):766-75. Epub 2000 Aug 17. — View Citation

Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, Robbins GK, D'Aquila RT, Goulder PJ, Walker BD. Immune control of HIV-1 after early treatment of acute infection. Nature. 2000 Sep 28;407(6803):523-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average of log10 HIV-1 RNA viral load		At Weeks 58 and 63
Primary	Frequency of Grade 3 or 4 systemic adverse events, the occurrence of a severe or life-threatening injection site adverse event, or death		Throughout study
Secondary	Distribution of plasma HIV RNA viral load		At Weeks 63 and 87
Secondary	Proportion of patients with controlled viremia and their respective distribution of plasma HIV RNA viral load		At Weeks 63 and 87
Secondary	Mean viral burden, defined as time-averaged area under the log10 HIV-1 RNA viral load curve		At Weeks 63 and 87
Secondary	HIV DNA levels		At Weeks 30, 38, 63, and 87
Secondary	HIV-1 DNA levels		At Weeks 30, 38, 46, 50, 63, and 87
Secondary	Magnitude and absolute change in CD4 and CD8 counts		At Weeks 63 and 87
Secondary	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		Through Week 30
Secondary	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		Through Week 30
Secondary	Breadth and magnitude of HIV-1- specific CD4 and CD8 cell responses		Throughout study
Secondary	Time to reach the specified virologic or immunologic criteria for reinitiating antiretroviral therapy after treatment interruption		Throughout study
Secondary	Frequency of Grade 3 or 4 systemic adverse events or the occurrence of a severe or life-threatening injection site adverse event, or HIV-related events, AIDS-defining infections, and death from time of vaccination		Throughout study
Secondary	Cell-associated infectivity in latently infected cells		At Week 63
Secondary	Cell-associated infectivity at Week 63 and immunologic responses		At Weeks 63 and 87

External Links

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