Human Immunodeficiency Virus (HIV) is a virus that attacks the immune system and can lead to acquired immunodeficiency syndrome (AIDS). While antiretroviral therapy (ART) has dramatically improved the prognosis for HIV-infected individuals, drug resistance and side effects continue to be major challenges.
Fusion inhibitors are a class of antiretroviral agents that target the early stages of HIV infection by blocking the fusion of the virus with the host cell membrane. In this article, we will review the current landscape of fusion inhibitors for the treatment of HIV, including approved drugs and those in clinical development. We will also discuss the challenges and future prospects for this class of antiretroviral agents.
There are currently two fusion inhibitors approved for the treatment of HIV: enfuvirtide (T-20) and ibalizumab (Trogarzo). Enfuvirtide is a peptide that binds to the viral glycoprotein gp41 and prevents the fusion of the virus with the host cell membrane. Ibalizumab is a monoclonal antibody that binds to the CD4 receptor on host cells and blocks the binding of the viral envelope protein gp120, thus preventing viral entry. Both drugs are administered by injection and are reserved for patients who have developed resistance to other classes of antiretroviral agents.
In addition to these approved drugs, there are several fusion inhibitors in clinical development for the treatment of HIV. One promising drug candidate is fostemsavir (ViiV Healthcare), a prodrug of temsavir that inhibits viral fusion by binding to the viral envelope protein gp120. Fostemsavir has demonstrated potent antiviral activity in clinical trials and was recently approved by the US Food and Drug Administration (FDA) for the treatment of HIV in heavily treatment-experienced patients.
Another drug candidate in clinical development is UB-421 (United Biopharma), a bispecific antibody that binds to both the CD4 receptor on host cells and the viral envelope protein gp120. UB-421 has shown promise in early clinical trials and has the potential to be a long-acting, subcutaneously administered therapy.
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