Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition
Creators: name: Takuva, S.
name: Mascola, J.R.
name: Frank, I.
name: Sista, N.
name: Huang, Y.
name: Randhawa, A.K.
name: Mukwekwerere, P.G.
name: Sanchez, J.
name: Bentley, C.
name: Gilbert, P.B.
name: Juraska, M.
name: Ledgerwood, J.E.
name: Mgodi, N.M.
name: deCamp, A.C.
name: Marshall, K.E.
name: Gonzales, P.
name: Piwowar-Manning, E.
name: Makhema, J.
name: Burns, D.N.
name: Hural, J.
name: Lazarus, E.M.
name: Sobieszczyk, M.E.
name: McElrath, M.J.
name: Lama, J.R.
name: Williamson, C.
name: Gray, G.
name: Karuna, S.T.
name: Edupuganti, S.
name: Rudnicki, E.
name: Kochar, N.
name: Laher, F.
name: Andrew, P.
name: Espy, N.
name: Gomez Lorenzo, M.M.
name: Corey, L.
name: Montefiori, D.C.
name: Morris, L.
name: Mullins, J.I.
name: Kublin, J.G.
name: Donnell, D.J.
name: Cohen, M.S.
name: Hinojosa, J.
name: Cabello, R.
name: Orrell, C.
name: Baden, L.R.
Publisher: name: Massachussetts Medical Society
Year: 2021

description: 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 &lt;1 μg 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.