Broadly neutralizing monoclonal antibodies (bNAbs) suppress HIV-1 RNA and may deplete residual viral reservoirs. We evaluated VRC01LS and 10-1074 as a treatment alternative to antiretroviral therapy (ART).
Children who received continuous ART from <7 days (and 1 child with intra-partum infection started at 31 days), and had HIV RNA <40 c/mL for ?24 weeks prior to entry, enrolled at >96 weeks of age. After at least 8 weeks of overlap with ART (the first 6 participants had 32 wks of overlap during a safety and PK phase), ART was held and treatment with dual VRC01LS and 10-1074 (dosed every 4 wks) was continued. HIV RNA was checked every 1-2 weeks and ART was restarted (and bNAbs discontinued) if >400 c/mL, or at 24 weeks; HIV RNA was checked weekly until <40 c/mL after re-starting ART.
Twenty-eight children entered the treatment component of the study while receiving lopinavir/ritonavir-based ART, at a median age of 3.6 (range 2.4, 5.6) years, and median CD4 count 1198 cells/mm3; 25 (89%) went on to the bNAb-only treatment phase (viral rebound occurred in 2 on the day of bNAb initiation and in 1 while on ART and bNAbs). Eleven children (44%, 95%CI 24-65%) maintained HIV RNA <40 c/mL through 24 weeks of bNAb-only treatment (including 1 with a single value of 234 c/mL at wk 16) and after ART re-start. Children with treatment success had favorable pre-intervention clinical and reservoir characteristics (Table 1); 5 of 6 (83%) with long bNAb/ART overlap succeeded. Fourteen children (56%) had viral rebound to >400 c/mL at a median of 4 (range 1, 20) weeks, and were immediately re-started on ART; median HIV RNA at re-start was 4.42 (range 2.87, 6.42) log10 c/mL. After failure, re-suppression to <40 c/mL occurred in all children, at a median of 4.1 (range 0.9-20.3) weeks from ART re-start. No infusion reactions occurred, and bNAbs were well-tolerated with only five grade 3 events (one neutropenia considered possibly study drug-related). PBMC HIV DNA change over time, and neutralization assay data for bNAbs at failure, are forthcoming.
In this proof-of-concept study, dual bNAb treatment with VRC01LS and 10-1074 maintained viral suppression for 24 weeks in the absence of ART in 44% of children, and was well-tolerated. Newer bNAb combinations with greater breadth and potency, used in children with favorable pre-treatment characteristics and possibly with longer bNAb/ART overlap, may improve treatment success for this novel ART-sparing strategy.