Use of cidofovir in a patient with severe mpox and uncontrolled HIV infection

Stafford, Adam; Rimmer, Stephanie; Gilchrist, Mark; Sun, Kristi; Davies, Ella; Waddington, Claire S.; Chiu, Christopher; Armstrong‐James, Darius; Swaine, Thomas; Davies, Frances; Gómez, Carlos H M; Kumar, Vagish; ElHaddad, Ahmad; Awad, Zaid; Smart, Christopher; Mora-Peris, Borja; Muir, David; Randell, Paul; Peters, Joanna R; Chand, Meera; Warrell, Clare E.; Rampling, Tommy; Cooke, Graham; Dhanji, Sara; Campbell, V; Davies, Carys Ann; Osman, Sana; Abbara, Aula

doi:10.1016/s1473-3099(23)00044-0

Cited by 24 publications

(23 citation statements)

References 37 publications

(59 reference statements)

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“…One of these patients even had greater than 10 vesicular lesions on the conjunctiva and had complete resolution after cidofovir treatment. Another case was reported in the United Kingdom, where a patient with poorly controlled HIV and Ludwig’s angina was treated with tecovirimat and subsequently with topical and intravenous cidofovir, after which he experienced significant improvement [ 42 ]. Fabrizio et al also described an HIV patient with severe mpox treated only with cidofovir.…”

Section: Discussionmentioning

confidence: 99%

Successful Outcome after Treatment with Cidofovir, Vaccinia, and Extended Course of Tecovirimat in a Newly-Diagnosed HIV Patient with Severe Mpox: A Case Report

Martinez

Frattaroli

et al. 2023

Vaccines

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Purpose: To report a case of severe mpox in a newly diagnosed HIV patient concerning Immune Reconstitution Inflammatory Syndrome (IRIS) and/or tecovirimat resistance and/or tecovirimat resistance and to describe the management approach in the setting of refractory disease. Case: 49-year-old man presented with 2 weeks of perianal lesions. He tested positive for mpox PCR in the emergency room and was discharged home with quarantine instructions. Three weeks later, the patient returned with disseminated firm, nodular lesions in the face, neck, scalp, mouth, chest, back, legs, arms, and rectum, with worsening pain and purulent drainage from the rectum. The patient reported being on 3 days of tecovirimat treatment, which was prescribed by the Florida department of health (DOH). During this admission, he was found to be HIV positive. A pelvic CT scan revealed a 2.5 cm perirectal abscess. Treatment with tecovirimat was continued for 14 days, along with an empiric course of antibiotics for treatment of possible superimposed bacterial infection upon discharge. He was seen in the outpatient clinic and initiated antiretroviral therapy (ART) with TAF/emtricitabine/bictegravir. Two weeks after starting ART, the patient was readmitted for worsening mpox rash and rectal pain. Urine PCR also returned positive for chlamydia, for which the patient was prescribed doxycycline. He was discharged on a second course of tecovirimat and antibiotic therapy. Ten days later, the patient was readmitted for the second time due to worsening symptoms and blockage of the nasal airway from progressing lesions. At this point, there were concerns for tecovirimat resistance, and after discussion with CDC, tecovirimat was reinitiated for the third time, with the addition of Cidofovir and Vaccinia, and showed an improvement in his symptoms. He received three doses of cidofovir and two doses of Vaccinia, and the patient was then discharged to complete 30 days of tecovirimat. Outpatient follow-up showed favorable outcomes and near resolution. Conclusion: We reported a challenging case of worsening mpox after Tecovirimat treatment in the setting of new HIV and ART initiation concerning IRIS vs. Tecovirimat resistance. Clinicians should consider the risk of IRIS and weigh the pros and cons of initiating or delaying ART. In patients not responding to first-line treatment with tecovirimat, resistance testing should be performed, and alternative options should be considered. Future research is needed to establish guidance on the role of Cidofovir and Vaccinia immune globulin and the continuation of tecovirimat for refractory mpox.

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Section: Discussionmentioning

confidence: 99%

Successful Outcome after Treatment with Cidofovir, Vaccinia, and Extended Course of Tecovirimat in a Newly-Diagnosed HIV Patient with Severe Mpox: A Case Report

Martinez

Frattaroli

et al. 2023

Vaccines

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“…Tecovirimat has good oral bioavailability and has one important adverse reaction reported, pulmonary embolus. Other adverse reactions are more common, and they include headache, dizziness, nausea, and vomiting (Stafford et al, 2023). Cidofovir, a nucleotidic analog and an antiviral drug that acts by inhibiting viral DNA polymerase, is known to exhibit nephrotoxicity.…”

Section: Antiviral Drugs Approved For the Treatment Of Monkeypox Infe...mentioning

confidence: 99%

“…It has been observed that, at low concentrations, this antiviral drug is capable of inhibiting the cytopathic effect of poxviruses. However, in order to inhibit other RNA and DNA viruses, a higher concentration is required ( Stafford et al, 2023 ). US CDC offers the latest recommendations, detailed guidelines, and a protocol for the access and use of tecovirimat in mpox virus infections and other non-variola orthopoxvirus infections, in both adults and children ( Centers for Disease Control and Prevention Center for Preparedness and Response Monkeypox Outbreak, 2022 ).…”

Section: Antiviral Drugs Approved For the Treatment Of Monkeypox Infe...mentioning

confidence: 99%

Section: Antiviral Drugs Approved For the Treatment Of Monkeypox Infe...mentioning

confidence: 99%

“…Unlike tecovirimat, it has poor oral bioavailability. Therefore, it is intravenously administered ( Stafford et al, 2023 ).…”

Section: Antiviral Drugs Approved For the Treatment Of Monkeypox Infe...mentioning

confidence: 99%

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Monkeypox: a global health emergency

et al. 2023

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Over the past 2 years, the world has faced the impactful Coronavirus Disease-2019 (COVID-19) pandemic, with a visible shift in economy, medicine, and beyond. As of recent times, the emergence of the monkeypox (mpox) virus infections and the growing number of infected cases have raised panic and fear among people, not only due to its resemblance to the now eradicated smallpox virus, but also because another potential pandemic could have catastrophic consequences, globally. However, studies of the smallpox virus performed in the past and wisdom gained from the COVID-19 pandemic are the two most helpful tools for humanity that can prevent major outbreaks of the mpox virus, thus warding off another pandemic. Because smallpox and mpox are part of the same virus genus, the Orthopoxvirus genus, the structure and pathogenesis, as well as the transmission of both these two viruses are highly similar. Because of these similarities, antivirals and vaccines approved and licensed in the past for the smallpox virus are effective and could successfully treat and prevent an mpox virus infection. This review discusses the main components that outline this current global health issue raised by the mpox virus, by presenting it as a whole, and integrating aspects such as its structure, pathogenesis, clinical aspects, prevention, and treatment options, and how this ongoing phenomenon is being globally approached.

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Molecular epidemiology, transmission and clinical features of 2022‐mpox outbreak: A systematic review

Sharif,

Alzahrani

et al. 2023

Health Science Reports

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Background and AimsThe 2022‐mpox outbreak has spread worldwide in a short time. Integrated knowledge of the epidemiology, clinical characteristics, and transmission of mpox are limited. This systematic review of peer‐reviewed articles and gray literature was conducted to shed light on the epidemiology, clinical features, and transmission of 2022‐mpox outbreak.MethodsWe identified 45 peer‐reviewed manuscripts for data analysis. The standards of the Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) Statement and Cochrane Collaboration were followed for conducting the study.ResultsThe case number of mpox has increased about 100 times worldwide. About 99% of the cases in 2022 outbreak was from non‐endemic regions. Men (70%–98% cases) were mostly infected with homosexual and bisexual behavior (30%–60%). The ages of the infected people ranged between 30 and 40 years. The presence of HIV and sexually transmitted infections among 30%–60% of cases were reported. Human‐to‐human transmission via direct contact and different body fluids were involved in the majority of the cases (90%–100%). Lesions in genitals, perianal, and anogenital areas were more prevalent. Unusually, pharyngitis (15%–40%) and proctitis (20%–40%) were more common during 2022 outbreak than pre‐2022 outbreaks. Brincidofovir is approved for the treatment of smallpox by FDA (USA). Two vaccines, including JYNNEOSTM and ACAM2000®, are approved and used for pre‐ and post‐prophylaxis in cases. About 100% of the cases in non‐endemic regions were associated with isolates of IIb clade with a divergence of 0.0018–0.0035. Isolates from B.1 lineage were the most predominant followed by B.1.2 and B.1.10.ConclusionThis study will add integrated knowledge of the epidemiology, clinical features, and transmission of mpox.

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Use of cidofovir in a patient with severe mpox and uncontrolled HIV infection

Cited by 24 publications

References 37 publications

Successful Outcome after Treatment with Cidofovir, Vaccinia, and Extended Course of Tecovirimat in a Newly-Diagnosed HIV Patient with Severe Mpox: A Case Report

Successful Outcome after Treatment with Cidofovir, Vaccinia, and Extended Course of Tecovirimat in a Newly-Diagnosed HIV Patient with Severe Mpox: A Case Report

Monkeypox: a global health emergency

Molecular epidemiology, transmission and clinical features of 2022‐mpox outbreak: A systematic review

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