In Vitro Antiviral Activity of Cabotegravir against HIV-2

Abstract

We examined the antiviral activity of the integrase inhibitor (INI) cabotegravir against HIV-2 isolates from INI-naive individuals. HIV-2 was sensitive to cabotegravir in single-cycle and spreading-infection assays, with 50% effective concentrations (EC₅₀s) in the low to subnanomolar range; comparable results were obtained for HIV-1 in both assay formats. Our findings suggest that cabotegravir should be evaluated in clinical trials as a potential option for antiretroviral therapy and preexposure prophylaxis in HIV-2-prevalent settings.

Keywords: HIV-2; PrEP; West Africa; antiretroviral therapy; cabotegravir; human immunodeficiency virus; treatment.

FIG 1

Antiviral activity of cabotegravir against HIV-1_NL4-3 and HIV-2_ROD9. All data in the figure are from single-cycle infections of MAGIC-5A cells. Error bars indicate ±1 SD and, when not visible, are smaller than the symbols. (A) Results from a single assay in which HIV-1_NL4-3 (gray circles) and HIV-2_ROD9 (black boxes) were tested head-to-head. Data points represent the amount of β-galactosidase activity produced in HIV-infected cabotegravir-treated cultures relative to HIV-infected solvent-only (i.e., no-drug) controls. Each point is the mean of two cultures that were maintained in parallel. Curves were generated using a sigmoidal regression equation (GraphPad Prism 6.0 software). Mean EC₅₀s from multiple assay runs with HIV-1_NL4-3 and HIV-2_ROD9 are shown in the inset. Values below the x axis indicate the total number of assay runs that were performed for each strain. The P value was calculated using Welch's t test. (B) EC₅₀s obtained for HIV-2_ROD9 tested against cabotegravir (CAB), dolutegravir (DTG), raltegravir (RAL), and elvitegravir (EVG). Data for raltegravir and dolutegravir are contemporaneous with the cabotegravir data set; data for elvitegravir were previously published (71). P values are from analysis of variance with Tukey's posttest.