Tokameh Mahmoudi

The session “Strategies for cure: Pitfalls, possibilities promise” covered results from several curative clinical studies, which while disappointing, provide important insight into the characteristics of the latent HIV reservoir, and point to the requirement of the immune system for killing but also long term control of the reservoir after ART.

Dr.Fidler presented results of the first “shock and kill” trial. No difference was observed in HIV reservoir between the cART alone or cART+T cell vaccine+vorinostat arms, indicating absence of reduction in reservoir size. Drs.Wensing and Nijhuis presented data on patients who had received SCT with CCR5D32 donor cells. In one patient, pre and post mortem reservoir analysis indicated that while undetected in PBMCs after SCT, HIV DNA was still present in ilium, spleen, liver and lung. In another patient, viral breakthrough occurred three weeks after SCT with a highly replicative CXCR4-tropic HIV variant, present in the patient as a minor variant before SCT. Dr.Wong tested a number of envelope pseudotypes and vpx variants to design a lentiviral platform that efficiently infect resting cells. Dr.DiMascio showed that short term cART +a4b7integrin antibody treatment of macaques, in contrast to a previous study, did not lead to post cART control of SIV replication.

The outcome of these curative clinical studies, although negative, provide important insights and data for further analysis of the latent reservoir, and better future cure strategies. These include possible need for better vaccine epitopes, limited potency of LRA vorinostat alone, functional importance of tissue as long standing viral reservoir, and need for coreceptor analysis in future CCR5-based SCT’s. Finally, as highlighted by Dr.Steve Deeks, curative clinical and primate studies point to viral rebound, even in cases of extremely low reservoirs, underlining the need for inclusion of therapeutic vaccines in curative efforts to kill the reservoir and control replication post cART.