Nasal monkeypox virus infection successfully treated with cidofovir in a patient newly diagnosed with HIV

Background

Most cases of monkeypox-virus (MPXV) infection are mild and self-limiting, and only supportive therapy is required. For severe infections or in patients at high risk of progression, antivirals like tecovirimat or cidofovir are available as treatment. ¹ Cidofovir (CDV) is a prodrug that inhibits the viral DNA polymerase, and it should be administered with probenecid to prevent dose-limiting nephrotoxicity.^2–4 There are no data about cidofovir treatment for MPXV in humans.^5–7

To our knowledge this is the first case describing the use of intravenous cidofovir in severe MPXV infection.

Case report

A 25 years-old Brazilian man presented to the emergency department with fever up to 39°C, nasal pain and dysphagia appearing one week before. He was a sex worker, with a history of drug use (cocaine and marijuana); no intravenous drug use, nor history of recent travel outside Italy were reported in the previous three years. He was diagnosed with HIV at a private medical center two weeks earlier, but he wasn’t linked to care yet. On admission, HIV-1 serology was confirmed positive, with HIV-RNA load of 2.6 × 10⁵ copies/mL and CD4⁺ T-cells count of 414/mm³ (18% of total lymphocytes, CD4+/CD8+ ratio 0.3). On physical examination, we observed nasal swelling and erythema with erythematous crusts on the columella; on the penile shaft, a round, superficially eroded, hard and totally asymptomatic erythematous lesion was observed. Moreover, a diffuse superficial lymph node enlargement was found.

Forty-eight hours later, asymptomatic vesicles appeared on the palms, on the lower limbs bilaterally, and in the inguinal folds with asynchronous development, evolving into superficial ulcers and/or crusts, while the nasal lesions evolved into erythematous and yellow crusts with purulent secretions, compatible with impetiginization (Figure 1). Vesicular exudates from lesions on the hands and nose, as well as pharyngeal, rectal swabs and a plasma sample, were collected and analyzed using polymerase chain reaction (PCR) to detect MPXV DNA. For molecular diagnosis we used a home-made real-time PCR using MPXV specific primers and probe for viral MPXV DNA detection as described elsewhere. Positive samples were confirmed using the Real-Star Orthopoxvirus PCR kit (Altona Diagnostics GmbH). All samples for MPXV were positive. Screening for other sexually transmitted diseases (STDs) showed positive serology for syphilis, while antibodies and nucleic acid amplification test on urine and on rectal swab for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum were negative. On the third day after admission, given the severe nasal pain, the high risk of sequelae and the concern about disfiguring scars on the nose, a systemic single dose of cidofovir, in association with probenecid, was administered intravenously at the dosage of 5 mg per kg (250 mg). The patient did not show any adverse event such as nephrotoxicity. At the same time, antiretroviral therapy was started (bictegravir/emtricitabine/tenofovir alafenamide 50/200/25 mg single tablet orally once daily); a single dose of sigmacillin 2.400.000 units was administered for primary syphilis and oral moxifloxacin 400 mg once daily for five days for the impetiginization of the nasal lesions.

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Figure 1.

Nasal lesions at the hospital admission.

The patient was discharged ten days after the admission with an almost complete resolution of the nasal and penile lesions and with complete regression of the systemic symptoms.

At the one month-follow-up visit, complete healing of the cutaneous lesions without scarring was observed (Figure 2).

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Figure 2.

Nasal lesion at the one month follow up visit.

Discussion

As already mentioned, no antiviral therapy has been approved for MPXV infection and limited data have been published on treatment with tecovirimat. ⁸ Boesecke et al. described a similar clinical case of MPXV infection involving the nose successfully treated with tecovirimat. ⁹ Tecovirimat was not available so we decided to use cidofovir. Early treatment may have a significative clinical impact, especially in immunocompromised patients. The literature available so far did not show differences in the clinical presentation of MPXV infection between people with or without HIV.^10,11 People with advanced and uncontrolled HIV infection can be at a higher risk of severe or prolonged MPXV disease and, in a recent case series of MPXV infections, two out of the three serious complications reported (one case of epiglottitis and one of myocarditis) were found in two people with HIV.^12,13

More data on the effectiveness and tolerability of the MPXV therapies are needed to confirm this finding. According to a recent Centers for Disease Control and Prevention (CDC) report that described an increase in the prevalence of HIV among people with MPXV infection, our clinical case emphasizes the importance to offer complete STD screening to MPXV infected patients, including HIV testing. We also emphasize the need of a pre-exposure prophylaxis (PrEP) counselling in sex workers as well as in other populations at risk. Indeed, even the diagnosis of a single STD could serve as an indicator for the screening of all the other STDs, which now include also MPXV.