Review Question - QID 101362

Both ganciclovir and zidovudine are associated with an increased risk of neutropenia.

Ganciclovir is an antiviral agent used as the first-line treatment for CMV retinitis. Zidovudine, a nucleoside reverse transcriptase inhibitor (NRTI), is a common component of the highly active antiretroviral therapy (HAART) regimen in HIV+ patients. Both of these medications disrupt DNA synthesis in hematopoietic stem cells, thereby leading to bone marrow suppression. Feared clinical manifestations associated with neutropenia include fever and recurrent infection.

Lesho et al. discuss the management of many of the common complications related to antiretroviral therapy. They conclude that NRTIs can cause neutropenia, anemia, pancreatitis, neuropathies, hypersensitivity reactions, and lactic acidosis.

Jaresko summarizes the various causes of neutropenia in HIV+ patients. These include a direct effect of the HIV infection, concomitant malignancies, hematologic toxicity of drug therapy, and opportunistic infections that can infiltrate the bone marrow and result in myelosuppression.

Illustration A summarizes common drug interactions with ganciclovir therapy (note that coadministration with zidovudine precipitates neutropenia).
Illustration B lists many of the common adverse effects associated with NRTI therapy.

Incorrect Answers:
Answer 1: Foscarnet is the 2nd-line therapy for CMV retinitis; it is associated with nephrotoxicity and electrolyte abnormalities but not neutropenia.
Answer 3: Efavirenz is a NNRTI that is more commonly associated with psychiatric side effects.
Answer 4: Ritonavir is a protease-inhibitor; this class of medications is more commonly associated with hyperlipidemia, hyperglycemia, and lipodystrophy (body fat redistribution)
Answer 5: Raltegravir is an integrase-inhibitor; this drug is relatively well tolerated and is associated with mild skin reactions and liver dysfunction.