title: Advances in human clinical trials of vaccines to prevent HIV/AIDS and other HIV prevention interventions.
abstract: Nearly three decades after the first description in 1981 of the syndrome eventually designated as AIDS, only five efficacy trials testing just three HIV vaccine concepts have been initiated. In 2007, an efficacy analysis was conducted for the first of a newer generation of candidate HIV/AIDS vaccines based entirely on cellular immunity. Data from this study, known as the Step Study, indicated that the vaccine neither protected against infection nor lowered viral loads after infection. Furthermore, certain vaccinees were at higher risk of HIV infection following vaccination. This article explores these disappointing and surprising outcomes, reviews earlier efficacy studies and more recent discovery research, and provides a critical analysis of the field. Other HIV prevention interventions are considered because their successful implementation may dramatically alter the milieu for future HIV vaccine field trials, particularly impacting study designs and increasing sample sizes if incidence falls.
authors.affiliation: Division of Infectious Diseases, Emory University, 603 Church Street, Decatur, GA 30030, USA. mark.mulligan@emory.edu
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
references.citation: Lancet. 2008 Jun 21;371(9630):2109-19
references.pmid: 18572080
references.citation: Clin Infect Dis. 2008 Jun 1;46(11):1769-81
references.pmid: 18433307
references.citation: Lancet. 1999 Sep 4;354(9181):795-802
references.pmid: 10485720
references.citation: Lancet. 2007 Feb 24;369(9562):657-66
references.pmid: 17321311
references.citation: J Infect Dis. 2005 Mar 1;191(5):654-65
references.pmid: 15688278
references.citation: J Infect Dis. 2005 Mar 1;191(5):666-77
references.pmid: 15688279
references.citation: Lancet. 2008 Nov 29;372(9653):1881-1893
references.pmid: 19012954
references.citation: AIDS Res Hum Retroviruses. 2001 Jul 1;17(10):901-10
references.pmid: 11461676
references.citation: Lancet. 2008 Dec 6;372(9654):1977-87
references.pmid: 19059048
references.citation: Science. 2008 Jul 25;321(5888):472
references.pmid: 18653850
references.citation: PLoS Med. 2005 Nov;2(11):e298
references.pmid: 16231970
references.citation: J Infect Dis. 2004 Aug 15;190(4):702-6
references.pmid: 15272397
references.citation: Lancet. 2007 Jul 21;370(9583):251-261
references.pmid: 17631387
references.citation: J Virol. 2005 Oct;79(19):12321-31
references.pmid: 16160159
references.citation: J Infect Dis. 2006 Dec 15;194(12):1661-71
references.pmid: 17109337
references.citation: J Acquir Immune Defic Syndr. 2007 Feb 1;44(2):203-12
references.pmid: 17106277
references.citation: Science. 2008 Jul 25;321(5888):530-2
references.pmid: 18653883
references.citation: Lancet. 2007 Feb 24;369(9562):643-56
references.pmid: 17321310
references.citation: N Engl J Med. 2000 Mar 30;342(13):921-9
references.pmid: 10738050
references.citation: N Engl J Med. 2008 Jul 31;359(5):463-72
references.pmid: 18669425
references.citation: Am J Public Health. 2007 Jan;97(1):133-43
references.pmid: 17138920
references.citation: JAMA. 2008 Aug 6;300(5):520-9
references.pmid: 18677024