Background:
The VRC01 broadly neutralizing monoclonal antibody (mAb), targeting the CD4 binding site of HIV-1, has been shown to decrease viremia and prevent infection with neutralization-sensitive strains. We investigated the impact of a single intravenous VRC01 infusion in acute HIV-1 infection in individuals who received antiretroviral therapy (ART) simultaneously or one week later.
Methods:
RV398 (NCT02591420) was a randomized placebo-controlled trial of 24 adults enrolled with acute HIV-1 infection in Thailand, Kenya, Uganda, and Tanzania. Eight participants were randomized to each of the three arms: 1) placebo infusion + immediate ART, 2) VRC01 40mg/kg + immediate ART, or 3) VRC01 40mg/kg + subsequent ART initiated on day 7. Infusions in arms 1 and 2 were blinded; study duration was 24 weeks. Primary objectives were to assess mAb safety and the change in plasma viremia through day 7.
Results:
Enrollment completed in September 2020 with 15 (63%) participants in Thailand and 9 (37%) in East Africa. Mean age (SD) was 23.4 (3.6) years; 14 participants (58%) were cis-men, 7 (29%) cis-women, and 3 (13%) transgender women. Twelve (50%) were recruited in Fiebig stages I-II, 6 (25%) in III, and 6 (25%) in IV-V. There was one grade 3 mAb-related transient AST elevation and no mAb-related serious adverse events (AEs). Solicited AEs were mild or moderate. We observed a significantly greater viral load reduction by day 7 in the immediate ART arms compared to the subsequent ART arm in pairwise comparisons (p=0.007 and 0.003, respectively) with the greatest (mean log10; CI) reduction in those receiving mAb + immediate ART (-1.61; -2.10,-1.07) followed by placebo + immediate ART (-1.52; -2.08,-1.04) and mAb + subsequent ART (-0.23; -0.82, 0.43). Median time to virologic suppression and mean area under the viral load curve followed the same arm ordering but were statistically similar across the three arms. Sequencing of HIV-1 genomes at baseline from 23/24 infections reflected the geographic diversity of the participants with env sequences corresponding to CRF01_AE (n=13) and subtypes A1 (6), B (2) and C (2).
Conclusions:
Initial results demonstrate the safety of VRC01 with ART in acute HIV infection and the feasibility of studying mAb interventions during AHI across diverse subtypes and geographies. Further studies, including viral isolate mAb sensitivity, are ongoing to identify the determinants of the limited impact of VRC01 on acute HIV-1 viremia.
Figure 1: Plasma Viremia Through Day 28