HIV‐1 Non Group‐M Phenotypic Susceptibility to Ibalizumab

The study assessed the phenotypic susceptibility of non group‐M human immunodeficiency virus type 1 (HIV‐1/non‐M) clinical isolates to ibalizumab, the first‐in‐class long‐acting CD4‐directed post‐attachment inhibitor. Thirty isolates were tested: 1 HIV‐1/M (reference strain BRU.HXB2), 2 HIV‐1/N, 26 HIV‐1/O and 1 HIV‐1/P. A phenotypic in vitro assay was performed by pre‐incubating peripheral blood mononuclear cells with ibalizumab, (1–10 000 ng/mL), then infected and incubated before quantifying viral load with RT‐PCR. IC 50 , maximum percent inhibition (MPI), and fold change (FC) were calculated. Potential N ‐glycosylation sites (PNGS) in the V5 loop, V2 loop length and the side chain at position 375 were investigated. Ibalizumab inhibited 22 HIV‐1/O and 1 HIV‐1/N strains, with a median IC 50 of 0.0413 (range: 6.19E10 −11 ; 16.8) ng/mL and a median MPI of 96.9 (range: 68.4; 99.3)%. The HIV‐1/P strain displayed potential resistance (IC 50 > 10 000 ng/mL; MPI < 25%). Interpretable results were not obtained for 4 HIV‐1/O and 1 HIV‐1/N strains under standardization criteria. PNGS numbers in the V5 loop ranged from 0 to 4 in tested isolates. Ibalizumab showed in vitro activity against all validated HIV‐1/O and HIV‐1/N isolates, whereas the HIV‐1/P strain exhibited potential natural resistance. No relationship was observed between PNGS number and susceptibility.