Reactions Weekly | 2021
Darunavir/emtricitabine/tenofovir-alafenamide/ritonavir/sulfadiazine
Abstract
Diffuse toxoplasma encephalitis due to worsening of subclinical toxoplasmosis secondary to immune reconstitution inflammatory syndrome and reduced renal function: case report A 62-year-woman developed diffuse toxoplasma encephalitis due to worsening of subclinical toxoplasmosis secondary to immune reconstitution inflammatory syndrome (IRIS) during treatment with emtricitabine/tenofovir-alafenamide, darunavir and ritonavir for HIV-1. Subsequently, she developed reduced renal function during treatment with sulfadiazine for diffuse toxoplasma encephalitis [routes and durations of treatments to reactions onsets not stated; not all frequencies of dose administration and outcomes stated]. The woman was admitted to a hospital in England in June 2019 with a gradual cognitive decline. Upon examination, she was confused and had a vesicular rash on her back and side. Head MRI revealed some small vessel disease but no signs of encephalitis. Viral PCR studies detected the presence of Varicella Zoster Virus (VZV) with all other testing negative. However, VZV encephalitis was ruled out due to absence of signs. She tested positive for HIV-1 antibody. Therefore, HIV encephalopathy was suspected as a contributor to the clinical picture. She was treated with 3 weeks of aciclovir and started receiving HIV treatment comprising emtricitabine/tenofovir-alafenamide [Descovy] 200mg/10mg, darunavir 800mg and ritonavir 100mg. Additionally, she received cotrimoxazole as Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis prophylaxis. After an initial recovery and return to functional baseline over 7 months, she exhibited a further decline in executive function, memory and speech disturbance over a period of 3 weeks, resulting in a second admission in February 2020. Her symptomatic foci appeared subcortical with excessive somnolence, short and mid-term memory deficit, paranoia and agitation. It was reported that her hearing had worsened. Initially, it was considered that her symptoms were due to an IRIS to her previous VZV infection and/or another as yet unidentified pathogen. The woman was treated with aciclovir while awaiting further investigations. Thorax, abdomen and pelvis CT scan revealed a small liver haemangioma. Admission MRI head with contrast showed evidence of ventriculitis and confluent white matter high signal change in both cerebral hemispheres with sparing of the subcortical U fibres, the thalami are unaffected. There was little change in the basal ganglia and subtle signal change in the brainstem was unchanged. Ependyma and cranial nerves 7 and 8 revealed abnormal enhancement bilaterally. The delayed onset of symptoms from the initiation of HIV treatment ruled out HIV encephalopathy as contributor to the imaging changes. CSF analysis showed evidence of Toxoplasma gondii infection; a negative IgM and positive dye test results suggested active infection. The complete CSF results panel, suggested an atypical presentation of toxoplasma encephalitis. Her treatment was started with pyrimethamine and sulfadiazine 1.5g four times a day. Additionally, she was prescribed folinic acid. However, she developed reduced renal function due to sulfadiazine. Therefore, sulfadiazine was changed to clindamycin. It was considered that her clinical symptoms (diffuse toxoplasma encephalitis) were secondary to IRIS leading to worsening of a subclinical toxoplasmosis that was present at HIV diagnosis. Therefore, darunavir and ritonavir were replaced with dolutegravir to maximise CNS penetration of her regimen. After 12 days of treatment, an improvement in her mental state and mobility was noted. Then, she was discharged. As the clindamycin was prophylactic for PCP, cotrimoxazole was held until the course was completed. Follow-up MRI with contrast repeated 6 weeks post admission showed a significant reduction in the ependymal enhancement throughout the ventricles. Periventricular and deep white matter T2 signal change was stable. Previous ventriculitis was resolved. A further MRI performed 8 months post admission showed further resolution of the ventriculitis, and improvement in white matter changes and ependymal enhancement. She consulted ear, nose and throat clinician to evaluate her hearing; this revealed asymmetrical sensorineural hearing loss that was worse on the right than the left. At the time of report writing, she was happy with her hearing and did not want hearing aids. Owing to clinical improvement and obvious changes to the MRI, a brain biopsy to support the Toxoplasma diagnosis was not performed.