Safety and Efficacy of a Three-Dose Regimen of an Adenoviral HIV Vaccine (MRKAd5 HIV-1 Gag/Pol/Nef) in HIV Uninfected South African Adults

Summary

The purpose of this study is to determine the safety, efficacy, and tolerability of a three-dose regimen of an adenovirus-based HIV-1 vaccine in healthy South African adults.

Timeline

Start

2007-01

Primary completion

2012-08

Completion

2012-08

Outcome

Missed primary endpoint

paper The MRKAd5 HIV-1 vaccine did not prevent HIV-1 infection or lower viral-load setpoint PMID 21570355 ↗

Publications

• Background Morgan C, Bailer R, Metch B, Koup R, Paranjape RS, Vardas E, Pape JW, Figueroa JP, Barroso, P, Kalichman A, Jaspan H, Lama J, Jack N, Russell N. International seroprevalence of neutralizing antibodies against adenovirus serotypes 5 and 35. AIDS Vaccine 2005. Montreal, September 7, 2005.
• Background Shiver JW, Emini EA. Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med. 2004;55:355-72. doi: 10.1146/annurev.med.55.091902.104344.
• 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.
• Results Gray GE, Allen M, Moodie Z, Churchyard G, Bekker LG, Nchabeleng M, Mlisana K, Metch B, de Bruyn G, Latka MH, Roux S, Mathebula M, Naicker N, Ducar C, Carter DK, Puren A, Eaton N, McElrath MJ, Robertson M, Corey L, Kublin JG; HVTN 503/Phambili study team. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis. 2011 Jul;11(7):507-15. doi: 10.1016/S1473-3099(11)70098-6. Epub 2011 May 11.
• Leitman EM, Hurst J, Mori M, Kublin J, Ndung'u T, Walker BD, Carlson J, Gray GE, Matthews PC, Frahm N, Goulder PJ. Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02. J Infect Dis. 2016 Aug 1;214(3):379-89. doi: 10.1093/infdis/jiw093. Epub 2016 Mar 6.
• Moodie Z, Metch B, Bekker LG, Churchyard G, Nchabeleng M, Mlisana K, Laher F, Roux S, Mngadi K, Innes C, Mathebula M, Allen M, Bentley C, Gilbert PB, Robertson M, Kublin J, Corey L, Gray GE. Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men. PLoS One. 2015 Sep 14;10(9):e0137666. doi: 10.1371/journal.pone.0137666. eCollection 2015.
• Gray GE, Moodie Z, Metch B, Gilbert PB, Bekker LG, Churchyard G, Nchabeleng M, Mlisana K, Laher F, Roux S, Mngadi K, Innes C, Mathebula M, Allen M, McElrath MJ, Robertson M, Kublin J, Corey L; HVTN 503/Phambili study team. Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study. Lancet Infect Dis. 2014 May;14(5):388-96. doi: 10.1016/S1473-3099(14)70020-9. Epub 2014 Feb 20.
• Latka MH, Fielding K, Gray GE, Bekker LG, Nchabeleng M, Mlisana K, Nielson T, Roux S, Mkhize B, Mathebula M, Naicker N, de Bruyn G, Kublin J, Churchyard GJ; HVTN 503 Phambili study team. Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women. PLoS One. 2012;7(4):e31387. doi: 10.1371/journal.pone.0031387. Epub 2012 Apr 19.

Drugs

Indications