Fourati and colleagues from Paris analysed PRBC and rectal tissue samples from five patients maintained on controlled ART (range: 7-13 years) with five treatment-naive patients, using the presence of in-frame stop codon mutations in RT as an indicator of replication defective virus.
They reported a high level of defective genomes (median 21%; range 15%-100%) in the treated patients with the percentage inversely linked to the calculated size of the viral reservoir measured by proviral HIV DNA (r2=0.24; p=0.033). No similar mutations were found in the naive patients. Most of the changes were related to APOBEC3-induced hypermutations.
The researchers proposed that their finding might support an accumulation of virus that is unable to replicate on ART, reaching a common viral extinction and that future use of proviral HIV DNA in reservoir sites in the context of cure research, should additionally measure whether this is replication competent.
Fourati S et al. HIV-1 genome is often defective in PBMCs and rectal tissues after long-term HAART as a result of APOBEC3 editing and correlates with the size of reservoirs. 20th Intl Drug Resistance Workshop, 5-9 June 2012, Sitges. Abstract 33. Antiviral Therapy 2012: 17 Suppl 1:A41.