Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.
(Journal Article;Multicenter Study)
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 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. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.).
Corey, L; Gilbert, PB; Juraska, M; Montefiori, DC; Morris, L; Karuna, ST; Edupuganti, S; Mgodi, NM; deCamp, AC; Rudnicki, E; Huang, Y; Gonzales, P; Cabello, R; Orrell, C; Lama, JR; Laher, F; Lazarus, EM; Sanchez, J; Frank, I; Hinojosa, J; Sobieszczyk, ME; Marshall, KE; Mukwekwerere, PG; Makhema, J; Baden, LR; Mullins, JI; Williamson, C; Hural, J; McElrath, MJ; Bentley, C; Takuva, S; Gomez Lorenzo, MM; Burns, DN; Espy, N; Randhawa, AK; Kochar, N; Piwowar-Manning, E; Donnell, DJ; Sista, N; Andrew, P; Kublin, JG; Gray, G; Ledgerwood, JE; Mascola, JR; Cohen, MS; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams,
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