Background: Heavily treated HIV-1 infected patients may have limited therapeutic
alternatives. In order to ensure sustained HIV-RNA suppression in these patients and to
improve current antiretroviral treatment regimens in the fight against multi-drug resistant
strains, new drugs are needed. Recently, two new drugs among the new generation of entry
inhibitors showed promises for both their characteristics and mechanism of action.
Objective: To outline ibalizumab (Patent: US20120121597A1) and fostemsavir (Patent:
US8871771) future applications in people living with multi-drug resistant HIV with few remaining
Methods: We analysed the available literature and data from ongoing clinical trials about
ibalizumab and fostemsavir.
Results: Ibalizumab is a new humanized monoclonal antibody. It acts as post-attachment
inhibitor by binding CD4 2nd domain of T lymphocyte and preventing HIV connection to
CCR5 or CXCR4 and has been recently approved by Food and Drug Administration in the
United States of America as a new intravenous antiretroviral agent for heavily treated HIV
adults with multi -drug resistant infection.
Fostemsavir (formerly BMS-663068), the oral prodrug of temsavir, is another attachment
inhibitor. It acts by preventing the viral connection to CD4 by binding gp120. This drug
showed encouraging results in heavily treated patients as add-on agent to current antiretroviral
regimens, in particular for subtype B virus. It is currently being investigated in a phase 3,
two-cohort (randomized and non-randomized), trial.
Conclusion: The history of ibalizumab and fostemsavir will be written in next years. Continuing
the research will be crucial to obtain evidence based guidelines for the management
of heavily treated HIV-1 infected patients with limited therapeutic options.