A 42-year-old man comes to the emergency department due to fever, abdominal pain, and explosive diarrhea. He has a history of HIV but has not been taking any medications. BMI is 18.2 kg/m². Abdominal examination is notable for right-sided tenderness to palpation. Laboratory results show a CD4 cell count of 38/mm³, leukopenia, and thrombocytopenia. A CT scan of the abdomen reveals colitis. Colonoscopy reveals areas of erosions and ulcerations; pathology demonstrates cells with viral intranuclear and intracytoplasmic inclusions. Antiviral therapy is initiated to treat the colitis with an intravenous agent that does not require intracellular activation and is known to bind in vitro with viral-encoded enzymes such as DNA polymerase, RNA polymerase, and reverse transcriptase. Which of the following agents did this patient most likely receive?

Question

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This patient with HIV likely has cytomegalovirus (CMV) colitis (intranuclear and intracytoplasmic inclusions), which, in some patients (eg, with ganciclovir resistance or refractory thrombocytopenia), is treated with foscarnet. Foscarnet is a pyrophosphate analog that does not require intracellular activation. It directly inhibits both DNA polymerase in herpesvirus and reverse transcriptase in HIV. Foscarnet must be administered intravenously. In addition to treating ganciclovir-resistant CMV infections, foscarnet is useful in patients who have acyclovir-resistant herpesvirus infections. Ganciclovir, a guanine nucleoside analogue structurally similar to acyclovir, is often used for CMV infections. However, it requires intracellular conversion by a virally encoded kinase and then by cellular kinases (Choice C). (Choice A) Acyclovir is a nucleoside analog that must be converted intracellularly to its monophosphate form by a virally encoded thymidine kinase. Cellular kinases convert the monophosphate form into a triphosphate form, which inhibits herpesvirus DNA polymerase-mediated replication. (Choice D) Lamivudine is a cytosine analog classified as a nucleoside reverse transcriptase inhibitor. It must be phosphorylated to its active form, lamivudine triphosphate, by intracellular kinases. Lamivudine inhibits HIV reverse transcription through viral DNA chain termination. (Choices E and F) Oseltamivir and saquinavir do not require intracellular activation but are not used for CMV infection. Oseltamivir is a sialic acid analogue inhibitor of influenza A and B virus neuraminidase. Saquinavir is an HIV protease inhibitor that prevents the cleavage of polyprotein precursors necessary for the generation of functional viral proteins. (Choice G) Sofosbuvir inhibits nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase needed for hepatitis C virus replication. It requires intracellular activation. Educational objective: Of all the antiviral agents that bind and inhibit DNA polymerase in herpesvirus and reverse transcriptase in HIV, the pyrophosphate analog foscarnet is one of few that do not require intracellular activation by viral or cellular kinases.

A 42-Year-Old Man Comes to the Emergency Department Due to Fever