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

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.

Timeline

Start

2004-06

Primary completion

2007-09

Completion

2011-05

Outcome

Missed primary endpoint

paper Vaccine benefit trends were seen for both primary end points, but they did not reach a prespecified significance level of P < or = 25. PMID 20662716 ↗

paper differences in HIV-1 RNA levels did not meet the prespecified level of significance. PMID 20662716 ↗

Publications

• Background 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. doi: 10.1038/415331a.
• Background 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. doi: 10.1073/pnas.221452198. Epub 2001 Oct 30.
• Background 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. doi: 10.1016/s0264-410x(02)00610-2.
• Results 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 immunization of HIV-1-infected persons with a replication-deficient adenovirus type 5 vaccine expressing the HIV-1 core protein. J Infect Dis. 2010 Sep 1;202(5):705-16. doi: 10.1086/655468.
• Li JZ, Heisey A, Ahmed H, Wang H, Zheng L, Carrington M, Wrin T, Schooley RT, Lederman MM, Kuritzkes DR; ACTG A5197 Study Team. Relationship of HIV reservoir characteristics with immune status and viral rebound kinetics in an HIV therapeutic vaccine study. AIDS. 2014 Nov 28;28(18):2649-57. doi: 10.1097/QAD.0000000000000478.
• Li JZ, Christensen JA, Wang H, Spritzler J, Kuritzkes DR; AIDS Clinical Trials Group A5197 Study Team. Evaluation of HIV-1 ambiguous nucleotide frequency during antiretroviral treatment interruption. J Acquir Immune Defic Syndr. 2012 Sep 1;61(1):19-22. doi: 10.1097/QAI.0b013e318264460f.
• Li JZ, Brumme CJ, Lederman MM, Brumme ZL, Wang H, Spritzler J, Carrington M, Medvik K, Walker BD, Schooley RT, Kuritzkes DR; AIDS Clinical Trials Group A5197 Study Team. Characteristics and outcomes of initial virologic suppressors during analytic treatment interruption in a therapeutic HIV-1 gag vaccine trial. PLoS One. 2012;7(3):e34134. doi: 10.1371/journal.pone.0034134. Epub 2012 Mar 30.
• Li JZ, Brumme ZL, Brumme CJ, Wang H, Spritzler J, Robertson MN, Lederman MM, Carrington M, Walker BD, Schooley RT, Kuritzkes DR; AIDS Clinical Trials Group A5197 Study Team. Factors associated with viral rebound in HIV-1-infected individuals enrolled in a therapeutic HIV-1 gag vaccine trial. J Infect Dis. 2011 Apr 1;203(7):976-83. doi: 10.1093/infdis/jiq143.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	MRKAd5 HIV-1 gag vaccine	Vaccine	—	Intramuscular

Indications