The best news for patients with CMV retinitis came shortly before the XI
International Conference on AIDS, when the FDA gave full approval to the use of
cidofovir (Vistide), a nucleotide analogue made by Gilead. Because of its long
half-life, cidofovir can be given as an intravenous infusion every two weeks for
maintenance therapy for CMV retinitis and, therefore, does not require
placement of a permanent central catheter. Unlike nucleoside analogues such as
ganciclovir, nucleotide analogues do not require an initial phosphorylation
before the drug is taken up into cells. Since resistance to ganciclovir is
usually due to viral mutations that reduce this phosphorylation step, there is
hope that cidofovir will be effective not only as first-line therapy but also
for patients with ganciclovir resistance. However, concerns remain about the
renal toxicity of cidofovir as well as the potential side effects (nausea,
fatigue, rash) of probenecid, which must be taken with cidofovir to reduce
renal toxicity. Logistic problems will also need to be worked out. The infusion
is lengthy because of the large volumes of saline hydration given with
cidofovir, and it is not clear whether home infusion is feasible for many
patients. Data presented at Vancouver indicated that cidofovir is effective for
relapsing CMV retinitis and that the 5 mg/kg dose every two weeks is more
effective than the 3 mg/kg dose, with no significant difference in side effects
(proteinuria, elevated creatinine, or neutropenia).
The sensitivity, specificity, and cost-effectiveness of various techniques that measure CMV, including DNA hybridization, pp65 antigenemia, PCR, and blood or urine cultures, will require much more extensive study before their clinical value is known. Data presented at Vancouver showed clearly that the peak activity of CMV assays does not always occur at the time of CMV disease. Serial assays are therefore necessary, potentially limiting the usefulness of CMV testing.
This article was provided by Johns Hopkins AIDS Service. It is a part of the publication Hopkins HIV Report.