A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model

Stably suppressed viremia during art is essential for establishing reliable simian models for hiv/aids. we tested the efficacy of a multidrug art (highly intensified art) in a wide range of viremic conditions (103-107 viral rna copies/ml) in sivmac251-infected rhesus macaques,and its impact on the viral reservoir. eleven macaques in the pre-aids stage of the disease were treated with a multidrug combination (highly intensified art) consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir),an integrase inhibitor (raltegravir),a protease inhibitor (ritonavir-boosted darunavir) and the ccr5 blocker maraviroc. all animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 rna copies/ml) after starting highly intensified art. by increasing the sensitivity of the assay to 3 rna copies/ml,viral load was still below the limit of detection in all subjects tested. importantly,viral dna resulted below the assay detection limit (<2 copies of dna/5*105 cells) in pbmcs and rectal biopsies of all animals at the end of the follow-up,and in lymph node biopsies from the majority of the study subjects. moreover,highly intensified art decreased central/transitional memory,effector memory and activated (hla-dr+) effector memory cd4+ t-cells in vivo,in line with the role of these subsets as the main cell subpopulations harbouring the virus. finally,treatment with highly intensified art at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle,thus leading to a persistent suppression of viremia in the absence of art. in conclusion,we show,for the first time,complete suppression of viral load by highly intensified art and a likely associated restriction of the viral reservoir in the macaque aids model,making it a useful platform for testing potential cures for aids. © 2012 shytaj et al.