Use of long-acting broadly neutralizing antibodies may delay human immunodeficiency virus (HIV) rebound following discontinuation of antiretroviral therapy

1. In this large randomized controlled trial, patients with human immunodeficiency virus (HIV) who received long-acting broadly neutralizing antibodies were able to delay HIV viral load rebound when off of antiretroviral therapy.

Evidence Rating Level: 1 (Excellent)

Long-acting broadly neutralizing antibodies (bNAbs) are being investigated as a strategy to maintain HIV suppression after discontinuation of antiretroviral therapy (ART), potentially providing a pathway toward prolonged ART-free viral control. This study reports secondary and exploratory analyses from the phase 2 RIO randomized, double-blind, placebo-controlled trial, which evaluated the long-acting bNAbs 3BNC117-LS and 10-1074-LS during analytical treatment interruption. Sixty-eight adult men living with HIV who had initiated ART during primary or early infection were randomized 1:1 to receive the two bNAbs (n=34) or placebo (n=34) before stopping ART. The investigators characterized the HIV reservoir using digital droplet polymerase chain reaction (ddPCR), assessed viral sensitivity to the antibodies, and examined viral rebound and evolution during treatment interruption. Early viral rebound before week 20 occurred in 8 participants in the bNAb group versus 30 in the placebo group (75% vs 11%; P < .001). Median time to ART restart was 45.4 weeks in the bNAb group compared with 4.6 weeks in the placebo group, and at 96 weeks, 7 of 29 participants (24%) receiving bNAbs remained off ART compared with 2 of 32 (6%) in the control group (P < .001). The investigators also found that greater baseline sensitivity of the viral reservoir to autologous antibodies and 10-1074 was associated with longer time to viral rebound. Overall, the findings suggest that long-acting bNAbs can substantially delay HIV rebound in selected individuals and that pre-existing host immunity and antibody sensitivity may influence the durability of ART-free viral control.

Click here to read this study in Nature Medicine

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