Background: It was recently reported that treatment with an antibody to the a4b7 integrin in rhesus macaques infected with SIVmac 239 having a stop codon in nef (SIVmac239nefstop) was associated with prolonged post-treatment suppression of viremia. The present study was undertaken to try to confirm and extend those observations.
Methods: Twenty-two Mamu-A001, Mamu-B008 and Mamu-B017 negative juvenile to adult Indian rhesus macaques (>4 kg or 3 yrs; mixed sex) were infected intravenously with 200 TCID50 SIVmac239nefstop (courtesy F. Villinger). At 5 weeks post-infection (wpi), combination anti-retroviral therapy (cART) was started with tenofovir, emtricitabine and L-870812. After 4 weeks of cART, animals received a total of 8 infusions every 3 weeks of primatized anti a4b7 antibody (n=12) or control antibody (n=10); cART was stopped at 18 wpi (after the fourth antibody infusion). Plasma SIV RNA levels had been monitored through at least 33 wpi at the time of abstract submission.
Results: Peak plasma SIV RNA levels averaged ~10^6 copies/ml in both groups. Sequencing confirmed the presence of the expected stop codon in nef in the challenge virus, with restoration to nef open by 5 wpi in all animals. Four weeks after cART initiation plasma SIV RNA levels were < 100 copies/ml in 10/12 experimental group animals and 10/10 controls. Three weeks following discontinuation of cART, plasma SIV RNA levels rose to above 100 copies/ml in 10/12 a4b7-treated animals and 8/10 controls. Fifteen weeks following cART interruption (33 wpi) mean plasma SIV RNA levels were ~ 10^4 copies/ml in both groups and not significantly different
Conclusions: In the present study, administration of an antibody to the a4b7 integrin in conjunction with short term cART was not associated with control of SIV replication following treatment cessation. Follow up studies to explore potential reasons for differences between the present findings and published results will focus on potential antidrug antibody responses and other possibilities.