Comparative overview of monoclonal antibodies under clinical investigation for human immunodeficiency virus-1 (HIV-1) treatment, including targets, mechanisms of action, and development status.
| Monoclonal antibody | Target | Mechanism of action | Status |
|---|---|---|---|
| Ibalizumab (Trogarzo) | Domain 2 of CD4 receptor | Blocks post-attachment conformational changes required for co-receptor recruitment; preserves MHC class II immune signalling | FDA approved (2018); European Medicines Agency (EMA) approved (2019) |
| VRC01 | CD4-binding site on gp120 | Broadly neutralising antibody (bnAb); directly neutralises diverse HIV-1 strains by blocking initial gp120-CD4 engagement | Phase II |
| Leronlimab (PRO 140) | CCR5 co-receptor | Competitively antagonises HIV entry by binding multiple extracellular domains of CCR5; inactive against CXCR4-tropic variants | Phase III |
| UB-421 | Domain 1 of CD4 receptor | Blocks initial gp120-CD4 binding at domain 1; mechanistically complementary to ibalizumab but may affect MHC class II signalling | Phase III |
| Vedolizumab | α4β7 integrin receptor | Reduces gut dissemination of HIV by inhibiting infected T-cell homing to the intestinal mucosa; immune-modulating strategy | Phase II |
| Combinectin (GSK3732394) | CD4 receptor and gp41 envelope glycoprotein | Long-acting multi-domain entry inhibitor incorporating one adnectin domain targeting CD4, a second adnectin domain targeting gp41, and an enfuvirtide-analogous peptide also targeting gp41 | Phase I |
| 10E8.4/iMab (bispecific) | gp41 membrane-proximal external region (MPER) and CD4 domain 2 | Bispecific antibody integrating ibalizumab CD4 binding with 10E8.4-mediated MPER neutralisation; high breadth and resistance barrier | Phase I |