Effectiveness of and Immune Response to HIV Vaccination Followed by Treatment Interruption in HIV Infected Patients

HIV Infections Clinical Trial

Official title:

A Phase II Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Antiretroviral Effect of Immunization With the MRK Ad5 HIV-1 Gag Vaccine in HIV-1 Infected Individuals Who Interrupt Antiretroviral Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00080106
• Other study ID #: A5197
• Secondary ID: 10014ACTG A5197
• Status: Completed
• Phase: Phase 2
• Start date: June 2004
• Est. completion date: May 2011

Study information

• Verified date: July 2013
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

HIV vaccines may help the immune systems of HIV infected patients better control the virus. The goal of this study is to determine whether patients on anti-HIV medications can stop taking those medications if they receive an HIV vaccine. While taking anti-HIV medications, participants will receive either an HIV vaccine or a placebo. Participants will then stop taking their anti-HIV medications and the study will compare the viral loads of participants who received the vaccine with the viral loads of participants who received the placebo.

Primary study hypotheses: 1)The Week 12 and Week 16 post-ART interruption geometric mean HIV-1 RNA levels will be lower among participants who had received MRK Ad5 vaccine prior to ART interruption than among participants who received placebo; 2) the time averaged area under the curve of the log10 HIV-1 RNA copies/ml versus day function in the 16 week post-ART interruption step will be lower among participants who received the MRK Ad5 vaccine prior to ART interruption than among participants who receive placebo.

Description:

Antiretroviral therapy (ART) has a significant impact on HIV disease; however, HIV cannot be cured with current drug regimens. While the majority of patients initially benefit from ART, drug regimens subsequently fail for many patients due to drug resistance, poor adherence, or toxicity. If given while HIV replication is kept in check by ART, an HIV vaccine may be able to generate an effective long-term immune response capable of controlling the virus, even if ART is discontinued.

The MRK Ad5 HIV-1 gag vaccine uses a replication-defective adenovirus vector and has been found safe in clinical trials of both HIV infected and HIV uninfected adults. This study will evaluate the ability of immunization with the MRK Ad5 HIV-1 gag vaccine to control HIV replication in individuals undergoing treatment interruption. The study will enroll individuals whose HIV replication has been successfully suppressed with ART for at least 2 years.

Participants in this study will be randomly assigned to receive either vaccine or placebo. Both vaccine and placebo will be injected into the upper arm muscle. Participants will take their antiretroviral medications during the first 3 months of the study. Injections will be given on Day 1, Week 4, and Week 26. A study nurse will call participants 1 or 2 days after each injection and participants will be asked to fill out a card with any reactions they have to the injections. About 3 months after the third injection, participants will stop taking their antiretroviral medications for 4 months. Participants will have study visits every 2 to 3 weeks while off medication. After 4 months, participants will have the option of restarting antiretroviral medications or continuing without medication. Participants will then have study visits every 2 months for 8 months. Study visits will include physical exams and blood collection.

All participants will continue to see their primary care provider for HIV treatment and will be restarted on antiretroviral medications if clinically indicated. Participants or their primary care provider will be contacted by phone for updates every 6 months for an additional 3.5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: May 2011
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria

• HIV infected

• On a stable antiretroviral medication regimen (no changes to treatment within 4 weeks of study entry)

• Viral load less than 50 copies/ml

• Viral suppression for 2 years prior to study entry (documented viral loads less than 500 copies/ml)

• CD4 count of 500 cells/mm3 or greater

• Ad5 neutralizing antibody less than 200 units at screening

• Willing to stop antiretroviral medications for at least 16 weeks post-vaccination

• Hepatitis B surface antigen negative

• Weight more than 110 lbs

• Willing to use acceptable methods of contraception

Exclusion Criteria

• Two consecutive viral loads of 500 copies/ml or greater at least 14 days apart during the 24 months prior to study entry

• Two consecutive CD4 counts less than 200 cells/mm3 before starting antiretroviral medications

• History of anaphylaxis

• Allergy to vaccine components

• History of cardiac, pulmonary, gastrointestinal, hepatic, renal, pancreatic, or neurologic disease which, in the opinion of the study official, will compromise study participation

• Pregnancy or breastfeeding

• Contraindication to intramuscular injection, such as anticoagulant therapy or thrombocytopenia

• Immune globulin or blood products within 3 months prior to study entry

• Live vaccine within 30 days prior to study entry

• Inactivated vaccine within 14 days prior to study entry

• Previous HIV vaccine

• History of an AIDS-defining illness. Patients with a history of Kaposi's sarcoma limited to the skin may participate.

• Currently taking drugs or other substances not approved by the FDA. Patients may be on antiretroviral agents not yet approved by the FDA as part of a clinical trial or through an expanded access program.

• Immunomodulatory agents (interferon, IL-2, GM-CSF, systemic corticosteroids, etc.) within 30 days prior to study entry

• Active alcohol or substance abuse which may interfere with the study

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• MRK Ad5 HIV-1 gag vaccine
MRK Ad5 HIV-1 gag vaccine injected into the upper arm muscle.

Other:
• Vaccine placebo
MRK Ad5 HIV-1 gag placebo vaccine injected into the upper arm muscle.

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico-AIDS CRS	San Juan
United States	IHV Baltimore Treatment CRS	Baltimore	Maryland
United States	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts
United States	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois
United States	Case CRS	Cleveland	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	Univ. of Texas Medical Branch, ACTU	Galveston	Texas
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana
United States	UCLA CARE Center CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	University of Minnesota, ACTU	Minneapolis	Minnesota
United States	Beth Israel Med. Ctr., ACTU	New York	New York
United States	Cornell CRS	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Stanford CRS	Palo Alto	California
United States	Pitt CRS	Pittsburgh	Pennsylvania
United States	The Miriam Hosp. ACTG CRS	Providence	Rhode Island
United States	AIDS Care CRS	Rochester	New York
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	Univ. of California Davis Med. Ctr., ACTU	Sacramento	California
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsd, Avrc Crs	San Diego	California
United States	Ucsf Aids Crs	San Francisco	California
United States	University of Washington AIDS CRS	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (4)

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

Ortiz GM, Wellons M, Brancato J, Vo HT, Zinn RL, Clarkson DE, Van Loon K, Bonhoeffer S, Miralles GD, Montefiori D, Bartlett JA, Nixon DF. Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects. Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13288-93. Epub 2001 Oct 30. — View Citation

Schooley RT, Spritzler J, Wang H, Lederman MM, Havlir D, Kuritzkes DR, Pollard R, Battaglia C, Robertson M, Mehrotra D, Casimiro D, Cox K, Schock B; AIDS Clinical Trials Group 5197 Study Team. AIDS clinical trials group 5197: a placebo-controlled trial of — View Citation

Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schleif WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature. 2002 Jan 17;415(6869):331-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analytical treatment interruption (ATI) HIV-1 RNA set-point		Throughout study
Primary	ATI log10 HIV-1 RNA copies/ml at all scheduled evaluations during Step II (ATI)		Throughout Step 2

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