“…Viral reservoirs examined by Quantitative Viral Outgrowth Assays (QVOA) or Tat/rev Induced Limiting Dilution Assays (TILDA) may not fully reactivated by stimulators, especially when the proviruses are located in the "gene desert" sites of chromosomes enriched in repressive chromatin marks 45,49,50,51 . Near full-length Individual proviral sequencing (FLIPS) and intact proviral DNA assay (IPDA) may also not accurately distinguish the functional proviral reservoir, as indicated by existence of intact proviral "quasispecies" and viral polymorphism 52,53 , di culties to predict production of replication-competent virions in the process of viral life cycle of HIV/SIV, functionality of viral genomes by various depletions and mutations 47,54,55,56 , or potential functional revertant mutation from de cient viral genome 57,58 , thereby lack of absolute gold standard approach to assess the genuine size of proviral reservoirs in the body 59 . Although qPCR may overestimate the viral reservoirs because of defective proviruses, total proviral DNA levels still re ects approximate size of intact viral genome, as intact viral genome accounts for ~11.7% in HIV+ patients and exists with higher fraction in SIV+ macaques on cART 60,61 .…”