HIV antibodies for treatment of HIV infection

While current combination antiretroviral therapy (ART) is highly effective at suppressing HIV replication, it is not curative. The virus persists in a latent reservoir within long-lived memory T cells, and lifelong adherence to daily medication is required. This paper explores the potential of using broadly neutralizing antibodies (bnAbs) and non-neutralizing antibodies as a new frontier in HIV therapeutics, aiming to move beyond simple viral suppression toward an HIV cure.

Unlike small-molecule drugs that typically target viral enzymes, antibodies can uniquely target the HIV envelope glycoprotein at two critical stages: when the virus seeks to enter new cells and when it is expressed from already infected cells. Beyond simple neutralization, these antibodies can recruit the immune system to clear infected cells through mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) and opsonization. These properties make them attractive candidates for both long-acting maintenance therapy and as tools to purge the latent viral reservoir.

Despite their promise, clinical trials have shown that HIV can rapidly evolve resistance to individual bnAbs, mirroring the challenges seen with early antiretroviral drugs. Consequently, the authors argue that successful antibody therapy will likely require combinations of agents with non-overlapping resistance patterns. Furthermore, researchers are developing advanced engineered molecules, such as bispecific antibodies (bsAbs), bispecific T cell engagers (BiTEs), and dual-affinity re-targeting (DART) molecules. These constructs are designed to simultaneously bind the virus and recruit cytotoxic effector cells, such as CD8+ T cells, to eliminate infected cells more efficiently.