Riociguat, a first-in-class
soluble guanylate cyclase stimulator, is approved for the treatment of
pulmonary arterial hypertension (PAH), a serious potential complication of human immunodeficiency virus (
HIV) infection. This open-label study investigated the pharmacokinetic
drug-drug interaction potential of antiretroviral
therapies on
riociguat exposure in HIV-infected adults. HIV-infected adults without PAH on stable antiretroviral regimens (
efavirenz/
emtricitabine/
tenofovir disoproxil,
emtricitabine/
rilpivirine/
tenofovir disoproxil,
elvitegravir/
cobicistat/
emtricitabine/
tenofovir disoproxil,
abacavir/dolutegravir/lamivudine, or a
ritonavir-boosted triple regimen) for ≥ 6 weeks received a single
riociguat dose (0.5 mg).
Riociguat pharmacokinetics and safety were assessed; pharmacokinetics was compared with historical healthy volunteer data. Of 41 participants treated (n = 8 in each arm, except n = 9 in the
ritonavir-boosted triple regimen arm), 40 were included in the pharmacokinetic analyses.
Riociguat median tmax was 1.00-1.27 h, with comparable maximum concentration (Cmax) across the five background antiretroviral groups.
Riociguat exposure was highest with
abacavir/dolutegravir/lamivudine, followed by
elvitegravir/
cobicistat/
emtricitabine/
tenofovir disoproxil > emtricitabine/
rilpivirine/
tenofovir disoproxil > ritonavir-boosted triple regimen > efavirenz/
emtricitabine/
tenofovir disoproxil;
riociguat area under the plasma concentration versus time curve (AUC) was approximately threefold higher with
abacavir/dolutegravir/lamivudine than
efavirenz/
emtricitabine/
tenofovir disoproxil. Compared with historical data,
riociguat exposure in HIV-infected adults was similar when co-administered with
efavirenz/
emtricitabine/
tenofovir disoproxil, slightly increased when administered with
ritonavir-boosted triple regimen and increased by approximately threefold when administered with
abacavir/dolutegravir/lamivudine.
Riociguat was well tolerated, with no new safety findings.
Riociguat was well tolerated in adults with HIV on stable background antiretroviral
therapy although an apparent increase in AUC of
riociguat was observed in patients receiving
abacavir/dolutegravir/lamivudine. Patients should be monitored closely during
riociguat initiation and dose adjustment for signs and symptoms of
hypotension.