title: Lessons learned from HIV vaccine clinical efficacy trials.
abstract: The past few years have witnessed many promising advances in HIV prevention strategies involving preexposure prophylaxis approaches. Some may now wonder whether an HIV vaccine is still needed, and whether developing one is even possible. The partial efficacy reported in the RV144 trial and the encouraging results of the accompanying immune correlates analysis suggest that an effective HIV vaccine is achievable. These successes have provided a large impetus and guidance for conducting more HIV vaccine trials. A key lesson learned from RV144 is that assessment of HIV acquisition is now a feasible and valuable primary objective for HIV preventive vaccine trials. In this article we review how RV144 and other HIV vaccine efficacy trials have instructed the field and highlight some of the HIV vaccine concepts in clinical development. After a long and significant investment, HIV vaccine clinical research is paying off in the form of valuable lessons that, if applied effectively, will accelerate the path toward a safe and effective vaccine. Together with other HIV prevention approaches, preventive and therapeutic HIV vaccines will be invaluable tools in bringing the epidemic to an end.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Day
authors.affiliation: HIV Vaccine Trials Network, Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave North, Seattle, WA 98109, USA. jkublin@fhcrc.org.
authors.forename: James G
authors.initials: JG
authors.lastname: Kublin
mesh_terms: D016915:AIDS Vaccines / Q000592:standards; D002986:Clinical Trials as Topic; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D012107:Research Design
chemical_list: D016915:AIDS Vaccines
references.citation: J Virol. 1999 May;73(5):4009-18
references.pmid: 10196297
references.citation: Stat Commun Infect Dis. 2011 Oct;3(1):
references.pmid: 23181167
references.citation: J Infect Dis. 2012 Jul 15;206(2):258-66
references.pmid: 22561365
references.citation: J Immunol. 2007 May 15;178(10):6596-603
references.pmid: 17475891
references.citation: Annu Rev Med. 2012;63:95-111
references.pmid: 21942424
references.citation: Vaccine. 2011 Jun 6;29(25):4285-92
references.pmid: 21435408
references.citation: J Virol. 2001 Feb;75(3):1301-11
references.pmid: 11152503
references.citation: Nat Med. 2009 Aug;15(8):876-8
references.pmid: 19620962
references.citation: Blood. 2011 Mar 10;117(10):2791-9
references.pmid: 21148083
references.citation: J Virol. 2003 Aug;77(15):8227-36
references.pmid: 12857891
references.citation: Antimicrob Agents Chemother. 2009 Feb;53(2):450-7
references.pmid: 19015347
references.citation: N Engl J Med. 2010 Dec 30;363(27):2587-99
references.pmid: 21091279
references.citation: AIDS Res Hum Retroviruses. 2013 Nov;29(11):1513-23
references.pmid: 23597282
references.citation: J Virol. 2012 Apr;86(8):4688-92
references.pmid: 22301150
references.citation: J Infect Dis. 2013 Sep 1;208(5):818-29
references.pmid: 23840043
references.citation: Prev Sci. 2014 Jun;15(3):268-76
references.pmid: 23446435
references.citation: J Clin Invest. 2012 Jan;122(1):25-7
references.pmid: 22201675
references.citation: J Virol. 2012 Feb;86(4):2239-50
references.pmid: 22156519
references.citation: Nat Med. 1999 Feb;5(2):194-203
references.pmid: 9930868
references.citation: AIDS Res Hum Retroviruses. 2012 Apr;28(4):400-4
references.pmid: 21902593
references.citation: Health Aff (Millwood). 2007 Jul-Aug;26(4):1147-58
references.pmid: 17630459
references.citation: Nat Med. 2011 Oct 11;17(10):1195-7
references.pmid: 21988997
references.citation: Nature. 2012 Jan 04;482(7383):89-93
references.pmid: 22217938
references.citation: J Infect Dis. 2011 Apr 1;203(7):969-75
references.pmid: 21402548
references.citation: J Acquir Immune Defic Syndr. 2012 Aug 1;60(4):405-13
references.pmid: 22421748
references.citation: J Virol. 2008 Jan;82(1):207-19
references.pmid: 17942549
references.citation: J Exp Med. 2008 Nov 24;205(12):2717-25
references.pmid: 18981239
references.citation: Clin Infect Dis. 2012 Jun;54(11):1615-7
references.pmid: 22437237
references.citation: J Exp Med. 2008 Oct 27;205(11):2537-50
references.pmid: 18838548
references.citation: PLoS One. 2010 Nov 11;5(11):e13540
references.pmid: 21085635
references.citation: Vaccine. 2011 Jul 18;29(32):5203-9
references.pmid: 21619905
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19940-5
references.pmid: 19918060
references.citation: N Engl J Med. 2012 Apr 5;366(14):1275-86
references.pmid: 22475592
references.citation: Science. 2009 Oct 9;326(5950):285-9
references.pmid: 19729618
references.citation: J Virol. 2010 Feb;84(3):1302-13
references.pmid: 19906907
references.citation: Clin Infect Dis. 2008 Aug 1;47(3):401-9
references.pmid: 18558875
references.citation: Curr HIV Res. 2006 Apr;4(2):199-208
references.pmid: 16611058
references.citation: PLoS One. 2011;6(8):e21225
references.pmid: 21857901
references.citation: AIDS. 2010 Jun 19;24(10):1598-601
references.pmid: 20549847
references.citation: J Infect Dis. 2004 Jan 15;189(2):286-91
references.pmid: 14722894
references.citation: Science. 2004 Jan 16;303(5656):316
references.pmid: 14726576
references.citation: N Engl J Med. 2009 Dec 3;361(23):2209-20
references.pmid: 19843557
references.citation: J Infect Dis. 2005 Mar 1;191(5):654-65
references.pmid: 15688278
references.citation: Sci Transl Med. 2011 May 4;3(81):81ra36
references.pmid: 21543722
references.citation: N Engl J Med. 2011 Aug 11;365(6):493-505
references.pmid: 21767103
references.citation: Curr Opin HIV AIDS. 2010 Sep;5(5):357-61
references.pmid: 20978374
references.citation: Vaccine. 2011 Oct 13;29(44):7794-800
references.pmid: 21821083
references.citation: Nature. 2007 Sep 6;449(7158):101-4
references.pmid: 17805298
references.citation: J Clin Epidemiol. 2001 Jan;54(1):68-85
references.pmid: 11165470
references.citation: Biometrics. 2006 Dec;62(4):1161-9
references.pmid: 17156291
references.citation: Vaccine. 2013 Sep 13;31(40):4398-405
references.pmid: 23859840
references.citation: J Infect Dis. 2005 Mar 1;191(5):666-77
references.pmid: 15688279
references.citation: J Infect Dis. 2011 Mar 1;203(5):610-9
references.pmid: 21282192
references.citation: Lancet. 2008 Nov 29;372(9653):1881-1893
references.pmid: 19012954
references.citation: Nature. 2012 Oct 18;490(7420):417-20
references.pmid: 22960785
references.citation: Nat Med. 2007 Jan;13(1):100-6
references.pmid: 17187074
references.citation: Vaccine. 2010 May 26;28 Suppl 2:B45-9
references.pmid: 20510743
references.citation: Science. 2001 Aug 24;293(5534):1503-6
references.pmid: 11520990
references.citation: Vaccine. 2012 Jun 22;30(30):4465-75
references.pmid: 22569124
references.citation: PLoS One. 2011;6(11):e25674
references.pmid: 22096477
references.citation: J Infect Dis. 2006 Dec 15;194(12):1661-71
references.pmid: 17109337
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11181-6
references.pmid: 21690411
references.citation: Clin Vaccine Immunol. 2010 Jul;17(7):1055-65
references.pmid: 20463105
references.citation: Lancet Infect Dis. 2011 Jul;11(7):507-15
references.pmid: 21570355
references.citation: Nat Med. 2009 Aug;15(8):873-5
references.pmid: 19620961
references.citation: J Infect Dis. 2010 Aug 15;202(4):595-605
references.pmid: 20608874
references.citation: Science. 2008 Jul 25;321(5888):530-2
references.pmid: 18653883
references.citation: J Virol. 2012 Jun;86(11):6279-85
references.pmid: 22491454
references.citation: J Infect Dis. 2007 Nov 1;196(9):1304-12
references.pmid: 17922394
references.citation: J Immunol. 2007 Mar 1;178(5):2746-54
references.pmid: 17312117
references.citation: Retrovirology. 2012 Sep 07;9:72
references.pmid: 22958464
references.citation: AIDS. 2011 Jan 14;25(2):153-8
references.pmid: 21150554
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10489-94
references.pmid: 18650391
references.citation: Nat Med. 2011 Mar;17(3):366-71
references.pmid: 21358627
references.citation: EMBO J. 2001 Apr 2;20(7):1726-38
references.pmid: 11285236
references.citation: Sci Transl Med. 2011 Apr 20;3(79):79ps13
references.pmid: 21508308
references.citation: Hum Vaccin. 2011 Jun;7(6):596
references.pmid: 21955676
references.citation: Science. 2010 Sep 3;329(5996):1168-74
references.pmid: 20643915
references.citation: Nat Med. 2000 Feb;6(2):207-10
references.pmid: 10655111
references.citation: Clin Investig (Lond). 2012 Mar;2(3):245-254
references.pmid: 23243491
references.citation: Biostatistics. 2008 Apr;9(2):263-76
references.pmid: 17704528
references.citation: JAMA. 2000 Nov 1;284(17):2193-202
references.pmid: 11056590
references.citation: Nature. 2011 Sep 22;477(7365):466-70
references.pmid: 21849977
references.citation: Cell. 2001 Sep 7;106(5):539-49
references.pmid: 11551502
references.citation: Cold Spring Harb Perspect Med. 2012 Jun;2(6):a007310
references.pmid: 22675663
references.citation: Science. 1995 Mar 24;267(5205):1820-5
references.pmid: 7892606
references.citation: J Acquir Immune Defic Syndr. 2013 Jul;63 Suppl 2:S183-6
references.pmid: 23764634
references.citation: Nat Med. 2012 Mar 06;18(3):346-7; author reply 347-8
references.pmid: 22395694
references.citation: Science. 2010 Aug 13;329(5993):856-61
references.pmid: 20616233
references.citation: Nat Med. 1999 Feb;5(2):204-10
references.pmid: 9930869