Abstract
Dear Sir,
Thank you for your case report on cytomegalovirus (CMV) retinitis in HIV infection by Adler et al. 1 We agree that managing CMV retinitis in severely immune compromised patients can constitute a major challenge.
We describe a 40-year-old man who was diagnosed with HIV in 2011, with a CD4 count of 50 cells/µL and a HIV viral load 10,000,000 copies/ml. At the time he was also diagnosed with diffuse large B cell lymphoma with liver metastasis. He received chemotherapy, achieved virological suppression on antiretroviral therapy and his CD4 count rose to 120 cells/µL. Six months later, he presented with a red, painful right eye. A diagnosis of CMV retinitis was confirmed. CMV load in the plasma was 400,000 copies/mL and in the cerebrospinal fluid (CSF) was 600,000 copies/mL. Intravitreal ganciclovir and foscarnet were administered with intravenous ganciclovir for three weeks, after which the patient was discharged home on maintenance oral valganciclovir at a dose of 900 mg daily. His CD4 count was 140 cells/µL, HIV viral load was undetectable and plasma CMV load was 16,000 copies/ml.
Ten weeks later, he presented with drop in his visual acuity from 6/38 to hand movements in the right eye. Examination revealed detachment of the right retina and active retinal inflammation in the left eye, together with ataxia and nystagmus. MRI brain ruled out CNS lymphoma. Of note, his CD4 count had dropped to 40 cells/µL, although HIV RNA remained undetectable. The CMV load in the plasma was 550,000 copies and 198,554 copies in the CSF. UL 97 mutations C592G and C607Y, associated with ganciclovir resistance 2 were detected in peripheral blood but not in CSF. Resistance testing on the earlier sample (with a CMV load of 16,000 copies/mL) was attempted but the sample was unable to be amplified. Intravitreal ganciclovir and foscarnet were administered to the left eye in conjunction with systemic antiviral therapy with intravenous foscarnet and ganciclovir. Subsequently, there was significant improvement in left retina with no evidence of active inflammation and four weeks later his CMV load in both plasma and CSF was undetectable. CD4 count increased to 90 cells/µL. Intravenous foscarnet monotherapy was continued for a further four weeks until CD4 count rose above 100 cells/µL.
This is a case of difficult-to-treat recurrent CMV retinitis. In the published 1 case, the use of oral valganciclovir given after receiving aggressive treatment (including three weeks of intravenous ganciclovir) was unable to prevent recurrence of CMV retinitis. Similarly, in the present case, CMV recurred after 10 weeks of appropriate treatment and resistance was detected in peripheral blood. We remain unsure as to why we were unable to detect resistance mutations in the CSF despite the high CMV load. When intravenous foscarnet was combined with ganciclovir there was significant reduction in CMV load and retinal improvement, in keeping with the experience of Adler et al. It is known that 3 maintenance therapy should be continued until CD4 >100 cells/µL and HIV viral load is undetectable; this posed a challenge in our case as immune reconstitution was very slow, possibly in part due to previous chemotherapy. This resulted in a prolonged hospital admission that was further complicated by an episode of line sepsis, possibly related to the prolonged use of intravenous ganciclovir, which itself can cause myelosuppression. 4
This report demonstrates the difficulties that may be faced when managing CMV retinitis in severely immunocompromised patients who are slow to immune reconstitution. There is risk of recurrent CMV retinitis, the management of which is problematic as effective treatment is needed, whilst avoiding further complications of developing resistance and the adverse effects of antivirals. It highlights the question of how long patients should continue on maintenance therapy if immune reconstitution is slow to progress. There has been found to be a correlation between CMV DNA levels becoming detectable and the progression of CMV retinitis in patients receiving maintenance therapy with ganciclovir. 5 One option may be to monitor CMV DNA levels whilst on maintenance therapy and switching to a treatment dose if they become detectable. However, greater experience in the management of similar cases will be needed in order to establish an answer to this question.