This was a retrospective, single-center study examining virologic outcomes among people with hypermutated PBMC DNA sequences containing APOBEC3 induced resistance mutations (APOMuts).  Three potential “at risk” regimen types were evaluated: 3-drug combinations containing a 3TC or FTC-based NRTI backbone paired with an NNRTI (with at least one drug impacted by APOMut in the RT gene); 2-drug combinations containing 3TC or FTC plus an INSTI (impacted by APOMut in either RT or INSTI); and 2-drug combinations containing an NNRTI plus INSTI (impacted by APOMut in either RT or INSTI).  PBMC DNA genotypes were ordered as part of routine clinical care, and the ANRS I MIE Resistance Study Group consensus Sanger protocol was used.  People with a history of relevant mutations identified on plasma RNA genotyping were excluded.  Investigators identified 38 people who were receiving or were started on therapy that could potentially be impacted by the APOMut detected.  The most prevalent APOMuts were M184I (n=21), M230I (n=11), and E138K (n=10).  Virologic suppression < 50 copies/mL was maintained in 34/38 (90%) of individuals.  For the 4 cases of virologic failure, investigators identified ART interruption or poor adherence: in 1 case, an emergent N155H was identified on plasma RNA genotype testing.

Given ongoing uncertainty around the role and interpretation of HIV proviral DNA testing (particularly given concerns related to quality control and test reporting practices), studies such as these may be helpful when considering whether and how to implement such testing into routine clinical care.  Although study size was limited, authors note their findings support the assessment that APOBEC3-mediated mutations do not actually compromise potentially impacted treatment regimens.  Further, they emphasize the value of collaborative approaches (e.g., multidisciplinary team meetings) involving virologists and clinicians to ensure accurately informed interpretation and application of test results when considering ART modification.