Prevalence of baseline virological risk factors of increased virological failure to CAB+RPV among ARV-naïve patients


BACKGROUND: Multivariable baseline factor analysis across CAB+RPV phase 3 studies recently showed that HIV-1 subtypes A6/A1, characterized by the L74I integrase (IN) polymorphism, and presence of RPV resistance-associated mutations (RAM), as well as body mass index, were associated with an increased risk of virological failure of this dual-therapy. The aim of this study was to describe the prevalence of CAB and RPV RAM among ARV-naive patients depending on the subtype.
METHODS: From 2010 to 2020, 4212 sequences from ARV-naïve patients with both RT and IN available sequences were collected from three large Parisian Academic Hospitals genotypic databases. CAB and RPV RAM were defined according to the ANRS algorithm (
RESULTS: Among 4212 sequences, 38.6% belonged to B subtype and the most prevalent non-B subtype was CRF02_AG (32.4%). Subtype A represented 5.1% of the sequences within 85.5% was of subtype A6/A1 (n=183/214). Overall, the presence of at least one CAB or RPV RAM was 16.2% and 14.3%, respectively. The overall prevalence of L74I in IN and E138A in RT was 13.0% and 3.2%, respectively, and stable over the decade. The frequency of L74I was significantly higher in non-B than in B subtypes (17.4% vs 6.0%, p<0.0001) with the highest prevalence observed in subtype A (49.5%). The frequency of E138A was significantly higher in non-B than in B subtypes (3.8% vs 2.2%, p=0.0003) and was 7.9% in subtype A (n=17/214). Sixteen patients (0.4%) displayed virus harboring both E138A and L74I polymorphisms. Considering genotypic resistance interpretation, using ANRS algorithm, 0.74% (n=31), 7.3% (n=306) and 0.09% (n=4) of sequences were resistant to cabotegravir, rilpivirine or both, respectively. Thus, 183 sequences were subtype A6/A1 and 244 were interpreted as resistant to RPV (after excluding those of subtype A6/A1) leading to 427 (10.1%) of sequences combining both baseline virological risk factors of CAB+RPV dual-therapy failure.
CONCLUSIONS: Among large sequences databases, when combining RPV RAMs and HIV-1 subtype A6/A1 prevalence, 10.1% of ARV-naive patients would not be eligible for CAB+RPV dual-therapy. These data re-emphasize the need of a pre-therapeutic genotypic resistance test to detect polymorphisms, transmitted drug resistance and to define HIV-1 subtype.