Share

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

Title
Prevalence of baseline virological risk factors of increased virological failure to CAB+RPV among ARV-naïve patients
Presenter
Charlotte Charpentier
Authors
C. Charpentier * (1), A. Storto (1), C. Soulié (2), V.M. Ferré (1), M. Wirden (2), V. Joly (3), S. Lambert-Niclot (4), L. Morand-Joubert (4), R. Landman (3), K. Lacombe (5), C. Katlama (6), J. Ghosn (3), A.-G. Marcelin (2), V. Calvez (2), D. Descamps (1).
Institutions
(1) Hôpital Bichat-Claude Bernard, Service de Virologie, Paris, France, (2) Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, France, (3) Hôpital Bichat-Claude Bernard, Service de Maladies Infectieuses et Tropicales, Paris, France, (4) Hôpital Saint-Antoine, Service de Virologie, Paris, France, (5) Hôpital Saint-Antoine, Service de Maladies Infectieusese et Tropicales, Paris, France, (6) Hôpital Pitié-Salpêtrière, Service de Maladies Infectieuses et Tropicales, Paris, France

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 (www.hivfrenchresistance.org).
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.