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

被引：347

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

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