Traditional Medicine Extracts of Gnidia sericocephala and Product Nkabinde in HIV-1 Latency Reversal: Insights from J-Lat Subtype B and J-Lat Subtype C Models

Abstract

The persistence of latent HIV-1 reservoirs in individuals on antiretroviral therapy (ART) remains a major barrier to cure, necessitating strategies such as "shock and kill" using latency-reversing agents (LRAs). However, current LRAs show limited clinical efficacy, highlighting the need for novel interventions. This study evaluated the in vitro latency-reversing potential of Product Nkabinde (PN) and <i>Gnidia sericocephala</i> using J-Lat A2 (subtype B) and J-Lat C clones T66 and T17 (subtype C) cells. Cell viability was assessed using flow cytometry with Live/Dead dye. Reactivation potential was further tested in combination with established LRAs: panobinostat, SAHA, and TNF-α. <i>G. sericocephala</i> induced dose-dependent latency reversal, with 26.1% of J-Lat A2 and 15.8% of J-Lat T66 cells GFP-positive at 106 µg/mL (<i>p</i> = 0.0001). Co-treatment with LRAs enhanced reactivation-34.6% with SAHA and 87.2% with TNF-α in J-Lat A2 cells, and 56.9% with SAHA and 65.4% with TNF-α in J-Lat T66 cells (<i>p</i> = 0.0001)-while maintaining cell viability above 90%. PN showed minimal activity (≤1.3% GFP-positive) and no effect in combination assays. Fractional inhibitory concentration index analysis revealed no synergistic interactions. Ex vivo, PN and <i>G. sericocephala</i> induced limited increases in HIV-1 gag RNA without substantial cytotoxicity. These findings demonstrate that <i>G. sericocephala</i> effectively reverses HIV-1 latency and potentiates TNF-α-induced reactivation, supporting its potential as a plant-derived LRA for future "shock and kill" HIV-1 cure strategies.