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1.
J Laryngol Otol ; 135(9): 755-758, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1747302

ABSTRACT

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome. METHOD: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted. RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019. CONCLUSION: The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Cushing Syndrome/chemically induced , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , HIV , Administration, Intranasal , Adrenal Cortex Hormones/administration & dosage , Adult , Cobicistat/administration & dosage , Cobicistat/adverse effects , Drug Interactions , Fluticasone/administration & dosage , Fluticasone/adverse effects , HIV Protease Inhibitors/administration & dosage , Humans , Male , Ritonavir/administration & dosage , Ritonavir/adverse effects
2.
AIDS Res Hum Retroviruses ; 37(4): 283-291, 2021 04.
Article in English | MEDLINE | ID: covidwho-1207222

ABSTRACT

The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Two hundred seventy-three patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch (p > .05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days for no-DRV/c, p = .9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p < .0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p = .03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.


Subject(s)
Anti-HIV Agents/therapeutic use , COVID-19/drug therapy , Cobicistat/therapeutic use , Darunavir/therapeutic use , Adult , Anti-HIV Agents/adverse effects , COVID-19/mortality , COVID-19/virology , Cobicistat/adverse effects , Darunavir/adverse effects , Drug Combinations , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification
3.
AIDS Res Hum Retroviruses ; 37(4): 283-291, 2021 04.
Article in English | MEDLINE | ID: covidwho-1096474

ABSTRACT

The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Two hundred seventy-three patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch (p > .05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days for no-DRV/c, p = .9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p < .0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p = .03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.


Subject(s)
Anti-HIV Agents/therapeutic use , COVID-19/drug therapy , Cobicistat/therapeutic use , Darunavir/therapeutic use , Adult , Anti-HIV Agents/adverse effects , COVID-19/mortality , COVID-19/virology , Cobicistat/adverse effects , Darunavir/adverse effects , Drug Combinations , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification
4.
Yonsei Med J ; 61(9): 826-830, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-745127

ABSTRACT

We retrospectively reviewed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who were admitted to an intensive care unit in Daegu, South Korea. The outcomes of patients who did (cases) or did not (controls) receive darunavir-cobicistat (800-150 mg) therapy were compared. Fourteen patients received darunavir-cobicistat treatment, and 96 received other antiviral therapy (controls). Overall, the darunavir-cobicistat group comprised patients with milder illness, and the crude mortality rate of all patients in the darunavir-cobicistat group was lower than that in the controls [odds ratio (OR) 0.20, 95% confidence interval (CI) 0.04-0.89, p=0.035]. After 1:2 propensity-score matching, there were 14 patients in the darunavir-cobicistat group, and 28 patients in the controls. In propensity score-matched analysis, the darunavir-cobicistat group had lower mortality than the controls (OR 0.07, 95% CI 0.01-0.52, p=0.009). In conclusion, darunavir-cobicistat therapy was found to be associated with a significant survival benefit in critically ill patients with SARS-CoV-2 infection.


Subject(s)
Anti-HIV Agents/therapeutic use , Cobicistat/therapeutic use , Coronavirus Infections/drug therapy , Darunavir/therapeutic use , HIV Protease Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Betacoronavirus , COVID-19 , Case-Control Studies , Cobicistat/administration & dosage , Cobicistat/adverse effects , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Critical Illness , Darunavir/administration & dosage , Darunavir/adverse effects , Female , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/adverse effects , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Republic of Korea/epidemiology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
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