-Phenyl-1-(phenylsulfonyl)-1-1,2,4-triazol-3-amine as a New Class of HIV-1 Non-nucleoside Reverse Transcriptase Inhibitor.

Highly active antiretroviral therapy (HAART) has revolutionized human immunodeficiency virus (HIV) healthcare, turning it from a terminal to a potentially chronic disease, although some patients can develop severe comorbidities. These include neurological complications, such as HIV-associated neurocognitive disorders (HAND), which result in cognitive and/or motor function symptoms. We now describe the discovery, synthesis, and evaluation of a new class of -phenyl-1-(phenylsulfonyl)-1-1,2,4-triazol-3-amine HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) aimed at avoiding HAND.

Small molecule modulation of the p75 neurotrophin receptor suppresses age- and genotype-associated neurodegeneration in HIV gp120 transgenic mice.

The persistence of HIV in the central nervous system leads to cognitive deficits in up to 50% of people living with HIV even with systemic suppression by antiretroviral treatment. The interaction of chronic inflammation with age-associated degeneration places these individuals at increased risk of accelerated aging and other neurodegenerative diseases and no treatments are available that effectively halt these processes. The adverse effects of aging and inflammation may be mediated, in part, by an increase in the expression of the p75 neurotrophin receptor (p75) which shifts the balance of neurotrophin signaling toward less protective pathways.