HIV-1 Non Group-M Phenotypic Susceptibility to Ibalizumab

Area of Science:

• Virology
• Immunology
• Pharmacology

Background:

• Non-group M human immunodeficiency virus type 1 (HIV-1/non-M) subtypes, particularly group O, are increasingly recognized.
• Understanding the susceptibility of these diverse HIV-1 strains to existing and novel antiretroviral therapies is crucial for treatment strategies.

Purpose of the Study:

• To assess the in vitro phenotypic susceptibility of clinical isolates of HIV-1/non-M (including groups N, O, and P) to ibalizumab.
• To investigate potential correlations between viral genetic markers (PNGS, V2 loop length) and ibalizumab susceptibility.

Main Methods:

• Phenotypic susceptibility testing using a standard in vitro assay with peripheral blood mononuclear cells.
• Quantification of viral load via RT-PCR to determine IC50, MPI, and fold change.
• Analysis of N-glycosylation sites in the V5 loop and V2 loop length.

Main Results:

• Ibalizumab demonstrated potent in vitro activity against validated HIV-1/O and HIV-1/N isolates, with median IC50 of 0.0413 ng/mL and median MPI of 96.9%.
• The single HIV-1/P isolate exhibited potential resistance, with IC50 > 10,000 ng/mL and MPI < 25%.
• No correlation was found between the number of PNGS in the V5 loop and ibalizumab susceptibility.

Conclusions:

• Ibalizumab shows significant in vitro activity against HIV-1/O and HIV-1/N clinical isolates.
• The HIV-1/P strain appears to possess natural resistance to ibalizumab.
• Susceptibility to ibalizumab in these non-group M strains is not associated with PNGS number in the V5 loop.