BACKGROUND: In addition to being naturally resistant to NNRTI and enfuvirtide, HIV-2 easily selects drug-resistance associated mutations to protease, NRTI and integrase inhibitors at time of virological failure, leading to multi-drug resistant (MDR) viruses. Ibalizumab (IBA) is a long-acting humanized monoclonal antibody that blocks entry of virus into the host cell. It is approved by the FDA and the EMA for treatment-experienced persons infected with MDR HIV-1. No data were available on the activity of IBA against HIV-2 isolates.
METHODS: Isolates from 6 HIV-2-infected persons (4 group B, 2 group A), the ROD HIV-2 group A reference strain and the BRU HIV-1 reference strain were assessed for IBA phenotypic susceptibility. We adapted a PBMC phenotypic assay. Briefly, PHA-activated PBMC were incubated with increasing concentrations of IBA for 1h, prior to infection. Two hours post-infection, cells were washed and then resuspended in complete RPMI media containing IBA. At day 4 post-infection, HIV-2 replication was assessed on cell supernatant using a qRT-PCR (Biocentric-HIV-2). Phenotypic susceptibility was assessed through 50% inhibitory concentrations (IC₅₀) and Maximum-Percent-Inhibition (MPI). All HIV-2 isolates were previously obtained by co-cultivation of PHA-activated PBMC pool obtained from healthy blood donors.
RESULTS: IBA inhibited viral replication for all seven HIV-2 isolates, with IC₅₀ ranging from 0.002 to 0.18µg/mL, and for the HIV-1 reference strain (IC₅₀=0.06µg/mL). MPI was below 80%, between 80 and 90%, and >90% for 2, 1 and 4 strains, respectively. The 2 isolates with the lowest MPI (74 and 77%) also had the highest IC₅₀ (0.18 and 0.09µg/mL, respectively).

HIV Isolate	IC50 (µg/mL)	Maximum Percent Inhibition (%)
BRU (HIV-1)	0.06	97
ROD (HIV-2)	0.01	97
Isolate#1	0.18	74
Isolate#2	0.02	91
Isolate#3	0.008	99
Isolate#4	0.014	99
Isolate#5	0.09	77
Isolate#6	0.002	83

CONCLUSIONS: These data demonstrate for the first time that IBA is active in vitro against both HIV-2 epidemic groups, with similar IC₅₀ and MPI to those observed for HIV-1. IBA could be included in therapies for HIV-2-infected-persons displaying MDR viruses, a more frequently observed situation in HIV-2 than in HIV-1. Clinical studies of IBA-based regimens in HIV-2-infected-patients are warranted.