Integrase inhibitors (INIs) are an important class of drugs for treating HIV-2
infection, given the limited number of drugs active against this virus. While the clinical efficacy of
raltegravir and
dolutegravir is well established, the clinical efficacy of
bictegravir for treating HIV-2 infected patients has not been determined. Little information is available regarding the activity of
bictegravir against HIV-2 isolates from patients failing
raltegravir-based
therapy. In this study, we examined the phenotypic and matched genotypic susceptibility of HIV-2 primary isolates from
raltegravir-naïve and
raltegravir-failing patients to
raltegravir,
dolutegravir, and
bictegravir, and to the new spiro-β-
lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of
bictegravir and BSS-730A. Isolates from
raltegravir-naïve patients were highly sensitive to all INIs and BSS-730A. Combined
integrase mutations E92A and Q148K conferred high-level resistance to
raltegravir, and E92Q and T97A conferred resistance to
raltegravir and
dolutegravir. The
antiviral activity of
bictegravir and BSS-730A was not affected by these mutations. BSS-730A displayed strong
antiviral synergism with
raltegravir. Mean IIP values at Cmax were similar for all INIs and were not significantly affected by resistance mutations. IIP values were significantly higher for BSS-730A than for INIs. The high IIP values of
bictegravir and BSS-730A for
raltegravir-naïve and
raltegravir-resistant HIV-2 isolates highlight their potential value for treating HIV-2
infection. Overall, the results are consistent with the high clinical efficacy of
raltegravir and
dolutegravir for HIV-2
infection and suggest a promising clinical profile for
bictegravir and BSS-730A.