**5.3. Selective cytolysis without viral reactivation**

Another interesting finding pertaining to reservoir eradication is the property of the gold complex drug 'auranofin' to selectively destroy the retroviral cellular reservoir. Although developed and used as an anti-rheumatic agent, the unique 'anti-memory T-cell effect' of auranofin has kindled interest in its possible role against HIV. Auranofin exerts its cytocidal action by inducing intracellular oxidative stress. The memory T-cells with low antioxidant defenses are highly vulnerable to the oxidative stress induced by auranofin and perish along with the integrated provirus. Combination of auranofin and buthionine sulfoximine, an inhibitor of glutathione synthesis is found to act synergistically by causing further imbalance in the redox pathways [133].

Auranofin has shown promising results in studies utilizing the simian AIDS model. Simian immunodeficiency virus (SIV) infected macaques, treated with a combination regimen of auranofin, buthionine and HAART have not only shown a prolonged post treatment drug free control of viremia but also developed enhanced cell mediated immunity with SIV specific cytotoxic CD8 T-cells following treatment suspension [134, 135]. However, well designed human clinical trials are required to know more about this anti-HIV reservoir compound before its flamboyance could be translated to practicality.

#### **5.4. Repression of latency**

With the mechanism exactly opposite to the shock and kill strategy, this strategy aims at achieving viremic control by keeping the viral reservoirs continually in the inactive state. As mentioned under the shock and kill strategy, concurrent activation of the gatekeeper kinase and NF-κB favours reactivation of the provirus. The compound Jun N-terminal protein kinase inhibitor-5 which is a potent inhibitor of the gatekeeper kinase strongly prevents viralreactiva‐ tion even upon strong stimulation of the NF-κB pathway under *in vitro* conditions. Inhibitors ofthe NF-κB pathway such as aloisineAand roscovitine also inhibit HIV reactivation to a lesser extent [128]. Various other molecules such as C-terminal truncated STAT5, Staf 50, prothymo‐ sin α, thioredoxin reductase, glucosamine and OKT-18 zinc finger protein have been identi‐ fied to prolong the proviralrepression. As the HIV protein 'Tat' activates proviral transcription after getting itself activated by acetylation, molecules that could specifically inhibit host cell acetylases which, eventually subdues the activity of the Tat peptide, can serve as attractive candidates for continuing viral repression [136]. Also, molecules that enhance the activity of the histone deacetylase if identified, could serve as suitable agents for this strategy [137].
