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Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

Publication ,  Journal Article
Gilbert, PB; Juraska, M; deCamp, AC; Karuna, S; Edupuganti, S; Mgodi, N; Donnell, DJ; Bentley, C; Sista, N; Andrew, P; Isaacs, A; Huang, Y ...
Published in: Stat Commun Infect Dis
January 2017

BACKGROUND: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. METHODS: The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. RESULTS: Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. CONCLUSIONS: The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention.

Duke Scholars

Published In

Stat Commun Infect Dis

DOI

ISSN

2194-6310

Publication Date

January 2017

Volume

9

Issue

1

Location

United States

Related Subject Headings

  • 4905 Statistics
  • 1108 Medical Microbiology
  • 0605 Microbiology
  • 0104 Statistics
 

Citation

APA
Chicago
ICMJE
MLA
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Gilbert, P. B., Juraska, M., deCamp, A. C., Karuna, S., Edupuganti, S., Mgodi, N., … Corey, L. (2017). Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials. Stat Commun Infect Dis, 9(1). https://doi.org/10.1515/scid-2016-0001
Gilbert, Peter B., Michal Juraska, Allan C. deCamp, Shelly Karuna, Srilatha Edupuganti, Nyaradzo Mgodi, Deborah J. Donnell, et al. “Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.Stat Commun Infect Dis 9, no. 1 (January 2017). https://doi.org/10.1515/scid-2016-0001.
Gilbert PB, Juraska M, deCamp AC, Karuna S, Edupuganti S, Mgodi N, et al. Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials. Stat Commun Infect Dis. 2017 Jan;9(1).
Gilbert, Peter B., et al. “Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.Stat Commun Infect Dis, vol. 9, no. 1, Jan. 2017. Pubmed, doi:10.1515/scid-2016-0001.
Gilbert PB, Juraska M, deCamp AC, Karuna S, Edupuganti S, Mgodi N, Donnell DJ, Bentley C, Sista N, Andrew P, Isaacs A, Huang Y, Zhang L, Capparelli E, Kochar N, Wang J, Eshleman SH, Mayer KH, Magaret CA, Hural J, Kublin JG, Gray G, Montefiori DC, Gomez MM, Burns DN, McElrath J, Ledgerwood J, Graham BS, Mascola JR, Cohen M, Corey L. Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials. Stat Commun Infect Dis. 2017 Jan;9(1).
Journal cover image

Published In

Stat Commun Infect Dis

DOI

ISSN

2194-6310

Publication Date

January 2017

Volume

9

Issue

1

Location

United States

Related Subject Headings

  • 4905 Statistics
  • 1108 Medical Microbiology
  • 0605 Microbiology
  • 0104 Statistics