In vitro phenotypic susceptibility of HIV-1 non-group M to CCR5 inhibitor (Maraviroc): TROPI-CO study

Abstract

The susceptibility of genetically divergent HIV-1 strains (HIV-1 non-M) from group O, N and P to the CCR5 co-receptor antagonist, Maraviroc (MVC) was investigated among a large panel of 45 clinical strains, representative of the genetic diversity. The results were compared to reference strains of HIV-1 group M (HIV-1/M) with known tropism. Among the non-M strains, a wide range of phenotypic susceptibilities to MVC was observed. The large majority of HIV-1/O strains (40/42) displayed a high susceptibility to MVC with median and mean IC50 values at 1.23 and 1.33 nM respectively, similar to the HIV-1/M R5 strain (1.89 nM). However, the 2 remaining HIV-1/O strains exhibited a lower susceptibility (IC50 at 482 and 496 nM), in accordance with their dual/mixed (DM) tropism. Interestingly, the 2 HIV-1/N strains demonstrated varying susceptibility patterns, despite always having relatively low IC50 values (2.87 and 47.5 nM). This emphasized the complexity of determining susceptibility solely based on IC50 values. Our study examined the susceptibility of all HIV-1 non-M groups to MVC and correlated these findings with virus tropism (X4, R5 or DM). The results confirm the critical significance of tropism determination before initiating MVC treatment in patients infected with HIV-1 non-M. Furthermore, we advocate for the consideration of additional parameters, such as the slope of inhibition curves, to provide a more thorough characterization of phenotypic susceptibility profiles.