ritonavir and Thromboembolism

COVID-19 has been linked to the development of many post-COVID-19 conditions (PCCs) after acute infection. Limited information is available on the effectiveness of oral antivirals used to treat acute COVID-19 in preventing the development of PCCs.. To measure the effectiveness of outpatient treatment of COVID-19 with nirmatrelvir-ritonavir in preventing PCCs.. Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir-ritonavir versus no treatment.. Veterans Health Administration (VHA).. Nonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022.. Nirmatrelvir-ritonavir treatment for acute COVID-19.. Cumulative incidence of 31 potential PCCs at 31 to 180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions and symptoms.. Eighty-six percent of the participants were male, with a median age of 66 years, and 17.5% were unvaccinated. Baseline characteristics were well balanced between participants treated with nirmatrelvir-ritonavir and matched untreated comparators. No differences were observed between participants treated with nirmatrelvir-ritonavir (. Ascertainment of PCCs using International Classification of Diseases, 10th Revision, codes may be inaccurate. Evaluation of many outcomes could have resulted in spurious associations with combined thromboembolic events by chance.. Out of 31 potential PCCs, only combined thromboembolic events seemed to be reduced by nirmatrelvir-ritonavir.. U.S. Department of Veterans Affairs.

Topics: Aged; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Female; Humans; Male; Retrospective Studies; Ritonavir; SARS-CoV-2; Thromboembolism; United States; Veterans

In spite of many ongoing attempts to repurpose existing antivirals, no drugs have emerged yet with the desirable activity against SARS-CoV-2. Hydroxychloroquine, lopinavir/ritonavir, remdesivir, umifenovir, favipiravir, ribavirin and beta-interferon-1 gave rise to variable but still inconsistent proof of clinical efficacy in the treatment of COVID-19. Pathogenetic studies have shown significant differences between commonly defined viral pneumonia and COVID-19 pulmonary disease. In severe forms, immune/inflammatory alterations reminiscent of disease forms like Macrophage Activation Syndrome (MAS) have been described, and therapeutic options other than anti-infective have been proposed and implemented, such as anti-inflammatory and anticoagulative agents. The thrombotic phenomena described in the pulmonary vascular bed of patients with severe COVID-19 suggest the administration of low-molecular weight heparin (LMWH) as standard measure in hospitalized patients with COVID-19.

Topics: Adenosine Monophosphate; Alanine; Anticoagulants; Antiviral Agents; Biomarkers; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Care; Disease Management; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Embolism; Endothelium, Vascular; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Interferon beta-1b; Lopinavir; Macrophage Activation; Pandemics; Pneumonia, Viral; Pulmonary Fibrosis; Randomized Controlled Trials as Topic; Ritonavir; Thromboembolism; Thrombophilia; Thrombosis

The potential for drug-drug interactions (DDIs) between direct oral anticoagulants and antiretroviral therapy (ART) is vast. Ritonavir and cobicistat are used as pharmacokinetic enhancers with either concurrent protease inhibitors or the integrase strand transfer inhibitor, elvitegravir, to optimize therapeutic concentrations by cytochrome P450 (CYP) inhibition. To date, only rivaroxaban and dabigatran have reported cases of use with ritonavir-boosted ART. Apixaban is metabolized similarly to rivaroxaban, but offers a dose reduction in the case of major DDIs. We report the successful use of reduced-dose apixaban to treat and prevent thromboembolic complications in six persons living with human immunodeficiency virus (HIV) on ritonavir- or cobicistat-boosted ART. This case series and available literature support the use of apixaban or dabigatran, depending on the boosted ART regimen.

Topics: Aged; Anti-HIV Agents; Cobicistat; Drug Interactions; Factor Xa Inhibitors; HIV Infections; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Ritonavir; Thromboembolism; Treatment Outcome

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