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. IC₅₀, 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 IC₅₀ 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 (IC₅₀ > 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.