ritonavir and Venous-Thrombosis

Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.

Topics: Adult; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Female; Humans; Hydroxychloroquine; Intracranial Thrombosis; Male; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Venous Thrombosis; Young Adult

To determine the indications for, rates of therapeutic anticoagulation during, and complications of warfarin therapy in HIV-infected individuals, in whom long-term anticoagulation is frequently indicated. To identify risk factors for nonoptimal anticoagulation and to determine if warfarin dosing is differentially affected by specific antiretroviral agents. Retrospective study of a dedicated anticoagulation program at one of the largest clinics for HIV-infected individuals in the United States. Seventy-three HIV-infected individuals on warfarin were followed for a total of 911 visits. The rate of therapeutic internation normalized ratio (INR) levels was 34.5% when including only visits at which patients were assessed to be adherent with warfarin. In multivariable analysis, injection drug use at baseline was an independent risk factor for subtherapeutic INR (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3-4.7, p=0.01). Additionally, warfarin adherence was protective of both subtherapeutic (OR 0.4, 95% CI 0.2-0.6, p<0.0001) and supratherapeutic (OR 0.5, 95% CI 0.3-0.9, p=0.02) INR status. Efavirenz-based antiretroviral regimens were associated with lower weekly warfarin doses (46 mg) to maintain therapeutic INR compared to lopinavir/ritonavir-based regimens (68 mg; p=0.01) and atazanavir/ritonavir-based regimens (71 mg; p=0.007). Consistently therapeutic warfarin therapy is difficult to achieve in HIV-infected individuals, even with a dedicated anticoagulation program. Adherence to warfarin therapy is important but rates of therapeutic INR levels are nonetheless low. Lower warfarin dosing was required for efavirenz compared to two commonly used protease inhibitor-based regimens. Because of these factors, the emergence of new oral anticoagulants is an important development for HIV-infected individuals who require long term anticoagulation therapy.

Topics: Adult; Alkynes; Anti-HIV Agents; Anticoagulants; Benzoxazines; Cyclopropanes; Drug Administration Schedule; Drug Interactions; Female; HIV Seropositivity; Humans; International Normalized Ratio; Lopinavir; Male; Medication Adherence; Patient-Centered Care; Retrospective Studies; Ritonavir; Thromboembolism; Treatment Outcome; United States; Venous Thrombosis; Warfarin

The authors report a case of an HIV type-1-infected patient concomitantly using highly active antiretroviral therapy and acenocoumarol anticoagulant for secondary prevention of recurrent venous thromboembolism. This is the first report of a possible drug interaction between efavirenz and atazanavir/ritonavir with acenocoumarol and also of the uncomplicated concurrent use of raltegravir with acenocoumarol.

Topics: Acenocoumarol; Alkynes; Anti-HIV Agents; Anticoagulants; Atazanavir Sulfate; Benzoxazines; Cyclopropanes; Drug Interactions; Drug Therapy, Combination; HIV Infections; Humans; Male; Middle Aged; Oligopeptides; Pyridines; Pyrrolidinones; Raltegravir Potassium; Reverse Transcriptase Inhibitors; Ritonavir; Venous Thrombosis

Vein thrombosis risk and pulmonary embolism seem to be more important among human immunodeficiency virus (HIV) infected patients.. We performed a retrospective study including 780 HIV positive patients followed-up between January 2000 and June 2005 at the University Hospital of Clermont-Ferrand.. Among the 780 HIV-infected patients, six cases of thromboembolic events were identified including, four with pulmonary embolism. All the patients were receiving lopinavir/ritonavir combination.. Although uncommon, pulmonary embolism occurs more frequently among HIV positive patients than in general population. Clinicians must remain aware about the possibility of the occurrence of a thromboembolic event especially during the first few months after introduction of the antiretroviral therapy.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cohort Studies; Female; Follow-Up Studies; France; HIV Protease Inhibitors; HIV Seropositivity; Humans; Lopinavir; Male; Middle Aged; Pulmonary Embolism; Pyrimidinones; Retrospective Studies; Ritonavir; Venous Thrombosis

To report a clinically severe interaction between ritonavir (RTV) and acenocoumarol resulting in a decrease in the anticoagulant effect severe enough to eventually preclude RTV administration.. An asymptomatic, HIV-infected, 46-year-old man with mitraortic prosthetic valves receiving acenocoumarol therapy started stavudine, lamivudine, and RTV 600 mg twice daily. His international normalized ratio (INR) decreased dramatically (the opposite of what should be expected). Although the acenocoumarol dose was progressively increased to 3 times the original dose, it was impossible to achieve the previous INR and RTV was withdrawn.. RTV is an inducer of the hepatic isoenzymes CYP1A2, CYP1A4, and CYP2C9/19 and leads to extensive metabolism of acenocoumarol that cannot be balanced by dose increases. This effect is the opposite of what was expected to occur, considering that RTV is also a strong inhibitor of most hepatic isoenzymes.. RTV severely decreases the anticoagulant effect of acenocoumarol. It must be added to the list of drugs that affect the action of oral anticoagulants, and it probably should be avoided in patients receiving acenocoumarol.

Topics: Acenocoumarol; Anticoagulants; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; International Normalized Ratio; Male; Middle Aged; Ritonavir; Venous Thrombosis

Topics: Adult; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Nelfinavir; Risk Factors; Ritonavir; Saquinavir; Venous Thrombosis

To report an unexpected decrease in warfarin effect following the addition of ritonavir to the medication regimen.. A 27-year-old patient with advanced HIV taking warfarin for an inferior vena cava thrombus was started on ritonavir, clarithromycin, and zidovudine. The international normalized ratio (INR) decreased over a period of weeks after the addition of ritonavir, clarithromycin, and zidovudine to the drug therapy regimen. The warfarin dosage was almost doubled in order to maintain a therapeutic INR. Months later, when ritonavir alone was discontinued, the INR rose rapidly and the warfarin dose requirements decreased significantly.. Potential interactions between warfarin and the protease inhibitors are described in the literature. Ritonavir has been shown to be a potent inhibitor of CYP3A4, an enzyme responsible for warfarin metabolism. Potentiation of warfarin effect and subsequent decrease in the warfarin dosage requirement was anticipated following ritonavir administration; however, the opposite occurred. The mechanism of the potential interaction between warfarin and ritonavir is not known, and may represent a complex, multidrug interaction. The paradoxical decrease in the INR is particularly intriguing.. Frequent, careful monitoring of warfarin is recommended when ritonavir therapy is initiated or discontinued in a patient taking warfarin. The potential for either an increase or decrease in the INR should be anticipated.

Topics: Adult; Anti-HIV Agents; Anticoagulants; Cytochrome P-450 Enzyme System; Drug Interactions; Female; HIV Infections; Humans; International Normalized Ratio; Ritonavir; Vena Cava, Inferior; Venous Thrombosis; Warfarin