Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition

被引：317

作者：

Corey, L. ^{[1
]}

Gilbert, P. B. ^{[1
]}

Juraska, M. ^{[1
]}

Montefiori, D. C. ^{[5
]}

Morris, L. ^{[8
,9
]}

Karuna, S. T. ^{[1
]}

Edupuganti, S. ^{[15
]}

Mgodi, N. M. ^{[16
]}

deCamp, A. C. ^{[1
]}

Rudnicki, E. ^{[1
]}

Huang, Y. ^{[1
]}

Gonzales, P. ^{[17
]}

Cabello, R. ^{[18
]}

Orrell, C. ^{[11
]}

Lama, J. R. ^{[19
]}

Laher, F. ^{[10
]}

Lazarus, E. M. ^{[10
]}

Sanchez, J. ^{[20
]}

Frank, I. ^{[22
]}

Hinojosa, J. ^{[21
]}

Sobieszczyk, M. E. ^{[23
]}

Marshall, K. E. ^{[1
]}

Mukwekwerere, P. G. ^{[16
]}

Makhema, J. ^{[24
]}

Baden, L. R. ^{[25
]}

Mullins, J. I. ^{[2
,3
,4
]}

Williamson, C. ^{[12
]}

Hural, J. ^{[1
]}

McElrath, M. J. ^{[1
]}

Bentley, C. ^{[1
]}

Takuva, S. ^{[1
,10
,13
]}

Lorenzo, M. M. Gomez ^{[26
]}

Burns, D. N. ^{[27
]}

Espy, N. ^{[1
]}

Randhawa, A. K. ^{[1
]}

Kochar, N. ^{[1
]}

Piwowar-Manning, E. ^{[29
]}

Donnell, D. J. ^{[1
]}

Sista, N. ^{[6
]}

Andrew, P. ^{[6
]}

Kublin, J. G. ^{[1
]}

Gray, G. ^{[1
,14
]}

Ledgerwood, J. E. ^{[28
]}

Mascola, J. R. ^{[28
]}

Cohen, M. S. ^{[7
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1100 Fairview Ave N, Seattle, WA 98109 USA

[2] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA

[3] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA

[4] Univ Washington, Dept Med, Seattle, WA USA

[5] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27706 USA

[6] FHI 360, Durham, NC USA

[7] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC 27515 USA

[8] Univ Witwatersrand, Natl Inst Communicable Dis, Natl Hlth Lab Serv, Johannesburg, South Africa

[9] Univ Witwatersrand, Antibody Immun Res Unit, Fac Hlth Sci, Johannesburg, South Africa

[10] Univ Witwatersrand, Fac Hlth Sci, Perinatal HIV Res Unit, Johannesburg, South Africa

[11] Univ Cape Town, Dept Med, Desmond Tutu HIV Ctr, Cape Town, South Africa

[12] Univ Cape Town, Div Med Virol, Cape Town, South Africa

[13] Univ Pretoria, Sch Hlth Syst & Publ Hlth, Fac Hlth Sci, Pretoria, South Africa

[14] South African Med Res Council, Tygerberg, South Africa

[15] Emory Univ, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA

[16] Univ Zimbabwe, Coll Hlth Sci, Clin Trials Res Ctr, Harare, Zimbabwe

[17] Hosp Nacl Mayo, Serv Enfermedades Infecciosas & Trop, Lima, Peru

[18] Asociac Civil Via Libre, Lima, Peru

[19] Asociac Civil Impacta Salud & Educ, Lima, Peru

[20] Univ Nacl Mayor San Marcos, Ctr Invest Tecnol Biomed & Medioambientales, Lima, Peru

[21] Assoc Civil Selva Amazon, Clin Res Site, Iquitos, Peru

[22] Univ Penn, Div Infect Dis, Perelman Sch Med, Philadelphia, PA 19104 USA

[23] Columbia Univ, Dept Med, Irving Med Ctr, Div Infect Dis, New York, NY USA

[24] Botswana Harvard AIDS Inst, Gaborone, Botswana

[25] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[26] NIAID, Vaccine Res Program, Div Aids, NIH, Rockville, MD USA

[27] NIAID, Prevent Sci Program, Div Aids, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[28] NIAID, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA

[29] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2021年 / 384卷 / 11期

关键词：

MONOCLONAL-ANTIBODIES; POTENT; BROAD; PRIMATES; VRC01; MARKS;

D O I：

10.1056/NEJMoa2031738

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear. METHODS We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay. RESULTS Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC80 <1 mu g per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates. CONCLUSIONS VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective.

引用

页码：1003 / 1014

页数：12

共 33 条

[1] Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption
Bar, K. J.
Sneller, M. C.
Harrison, L. J.
Justement, J. S.
Overton, E. T.
Petrone, M. E.
Salantes, D. B.
Seamon, C. A.
Scheinfeld, B.
Kwan, R. W.
Learn, G. H.
Proschan, M. A.
Kreider, E. F.
Blazkova, J.
Bardsley, M.
Refsland, E. W.
Messer, M.
Clarridge, K. E.
Tustin, N. B.
Madden, P. J.
Oden, K. S.
O'Dell, S. J.
Jarocki, B.
Shiakolas, A. R.
Tressler, R. L.
Doria-Rose, N. A.
Bailer, R. T.
Ledgerwood, J. E.
Capparelli, E. V.
Lynch, R. M.
Graham, B. S.
Moir, S.
Koup, R. A.
Mascola, J. R.
Hoxie, J. A.
Fauci, A. S.
Tebas, P.
Chun, T-W
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (21) : 2037 - 2050
[2] Centers for Disease Control and Prevention, 2020, HIV SURV REP, V31
[3] Safety, Tolerability, and Pharmacokinetics of the Broadly Neutralizing Human Immunodeficiency Virus (HIV)-1 Monoclonal Antibody VRC01 in HIV-Exposed Newborn Infants
Cunningham, Coleen K.
McFarland, Elizabeth J.
Morrison, R. Leavitt
Capparelli, Edmund, V
Safrit, Jeffrey T.
Mofenson, Lynne M.
Mathieson, Bonnie
Valentine, Megan E.
Perlowski, Charlotte
Smith, Betsy
Hazra, Rohan
Purdue, Lynette
Muresan, Petronella
Harding, Paul A.
Mbengeranwa, Tapiwa
Robinson, Lisa-Gaye
Wiznia, Andrew
Theron, Gerhard
Lin, Bob
Bailer, Robert T.
Mascola, John R.
Graham, Barney S.
[J]. JOURNAL OF INFECTIOUS DISEASES, 2020, 222 (04) : 628 - 636
[4] Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design
Diskin, Ron
Scheid, Johannes F.
Marcovecchio, Paola M.
West, Anthony P., Jr.
Klein, Florian
Gao, Han
Gnanapragasam, Priyanthi N. P.
Abadir, Alexander
Seaman, Michael S.
Nussenzweig, Michel C.
Bjorkman, Pamela J.
[J]. SCIENCE, 2011, 334 (6060) : 1289 - 1293
[5] Edupuganti S, 2021, J ACQUIR IMMUNE DEFI
[6] Gilbert Peter B, 2017, Stat Commun Infect Dis, V9, DOI 10.1515/scid-2016-0001
[7] Inferences on relative failure rates in stratified mark-specific proportional hazards models with missing marks, with application to human immunodeficiency virus vaccine efficacy trials
Gilbert, Peter B.
Sun, Yanqing
[J]. JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS, 2015, 64 (01) : 49 - 73
[8] Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine
Hammer, Scott M.
Sobieszczyk, Magdalena E.
Janes, Holly
Karuna, Shelly T.
Mulligan, Mark J.
Grove, Doug
Koblin, Beryl A.
Buchbinder, Susan P.
Keefer, Michael C.
Tomaras, Georgia D.
Frahm, Nicole
Hural, John
Anude, Chuka
Graham, Barney S.
Enama, Mary E.
Adams, Elizabeth
DeJesus, Edwin
Novak, Richard M.
Frank, Ian
Bentley, Carter
Ramirez, Shelly
Fu, Rong
Koup, Richard A.
Mascola, John R.
Nabel, Gary J.
Montefiori, David C.
Kublin, James
McElrath, M. Juliana
Corey, Lawrence
Gilbert, Peter B.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (22) : 2083 - 2092
[9] Passive and active antibody studies in primates to inform HIV vaccines
Hessell, Ann J.
Malherbe, Delphine C.
Haigwood, Nancy L.
[J]. EXPERT REVIEW OF VACCINES, 2018, 17 (02) : 127 - 144
[10] Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments
Hraber, Peter
Rademeyer, Cecilia
Williamson, Carolyn
Seaman, Michael S.
Gottardo, Raphael
Tang, Haili
Greene, Kelli
Gao, Hongmei
LaBranche, Celia
Mascola, John R.
Morris, Lynn
Montefiori, David C.
Korber, Bette
[J]. JOURNAL OF VIROLOGY, 2017, 91 (19)

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