Anti-gp120 CD4-induced antibodies are associated with CD4 depletion in vitro and in heavily treatment-experienced people with HIV. Fostemsavir treatment re

Ein internationales Forschungsteam hat einen breit neutralisierenden Antikörper entdeckt, der gegen nahezu alle bekannten HIV-Varianten wirksam ist. I...

Fostemsavir, a prodrug of the first-in-class gp120-directed attachment inhibitor temsavir, is indicated in combination with other antiretrovirals for the treatm...

There are approximately 40.8 million people living with HIV-1 (PLWH) worldwide, with an estimate of about 1.3 million new HIV-1 infections in 2024, highlighting the urgent need for an effective HIV-1 ...

The HIV protein gp120 amplifies spinal nerve receptors, providing a target to reverse chronic pain.

HIV-1 infection begins with Env-gp120 binding to the CD4 receptor and CD4-triggered Env conformational changes that enable viral entry. To identify key Env s...

AbstractFostemsavir, a prodrug of the first-in-class gp120-directed attachment inhibitor temsavir, is indicated in combination with other antiretrovirals for the treatment of multidrug-resistant HIV-1 in adults who are heavily treatment-experienced (HTE). Temsavir binds to HIV-1 gp120, close to the CD4 binding site, preventing the initial interaction of HIV-1 with CD4 on the host cell. Amino acid substitutions at four positions in gp120 have been identified as important determinants of viral susceptibility to temsavir (S375H/I/M/N/T/Y, M426L/P, M434I/K, M475I), with a fifth position (T202E) recently described. For most currently circulating group M HIV-1 subtypes, the prevalence of these resistance-associated polymorphisms (RAPs) is low. As with many other antiretrovirals, the impact of RAPs is modified by other changes in the target molecule. Different regions of gp120 interact to modify the temsavir binding pocket, with multiple amino acids playing a role in determining susceptibility. Extensive variability of HIV-1 gp120 means the susceptibility of clinical isolates to temsavir is also highly variable. Importantly, in vitro measurement of the susceptibility of clinical isolates to temsavir does not necessarily capture the range of susceptibilities of the heterogeneous mix of viruses generally present in each isolate. Due to these factors and limited phenotypic clinical data, thus far, no relevant phenotypic cutoff or genotypic algorithms have been derived that reliably predict response to fostemsavir-based therapy in individuals who are HTE; therefore, pre-treatment temsavir resistance testing may be of limited benefit. In the phase III BRIGHTE study, re-suppression after virologic failure was observed in some participants despite treatment-emergent genotypic and/or phenotypic evidence of reduced temsavir susceptibility, and substantial CD4+ T-cell count increases occurred even among participants with HIV-1 RNA ⩾40 copies/mL at Week 240. Clinical management of people who are HTE and experience virologic failure during treatment with fostemsavir-based regimens requires an individualized approach with consideration of potential benefits beyond virologic suppression.