Oral valganciclovir is as effective as intravenous ganciclovir for induction treatment of CMV retinitis
Graham McKerrow, HIV i-base
Orally administered valganciclovir appears to be as effective as intravenous ganciclovir for induction treatment and is convenient and effective for the long term management of cytomegalovirus (CMV) retinitis in patients with AIDS, according to the results of a randomised trial reported in the 11 April issue of the New England Journal of Medicine.
Dr Daniel F Martin and colleagues at the Valganciclovir Study Group write: “The results of our study indicate that a twice-daily dose of 900mg of oral valganciclovir for induction therapy in patients with cytomegalovirus retinitis has an efficacy and safety profile that is similar to the profile for intravenous ganciclovir. The proportions of patients with progression of retinitis during the first four weeks were similar for the two regimens.”
CMV retinitis remains the leading cause of loss of sight in people with AIDS. Induction therapy with ganciclovir, foscarnet or cidofovir, followed by maintenance therapy can effectively make CMV retinitis inactive. If recovery of immune function is not possible, indefinite treatment is needed, and an indwelling catheter to facilitate regular intravenous medication may be required. The cost, risk of sepsis, and effect on quality of life of having a permanent indwelling catheter provoked the search for an orally administered treatment.
Valganciclovir is an orally administered prodrug that is rapidly hydrolysed to ganciclovir. Dr Martin’s team compared the effects of oral valganciclovir with those of intravenous ganciclovir as induction therapy for newly diagnosed CMV retinitis in 160 patients with AIDS.
Eighty patients were randomly assigned to each treatment group. Of the patients who could be evaluated, seven of 70 assigned to intravenous ganciclovir (10.0%) and seven of 71 assigned to oral valganciclovir (9.9%) had progression to CMV retinitis during the first four weeks.
Forty-seven of 61 patients (77.0%) assigned to intravenous ganciclovir, and 46 of 64 (71.9%) assigned to valganciclovir had a satisfactory response to induction therapy.
The median times to progression of retinitis were 125 days in the group assigned to intravenous ganciclovir and 160 days in the group assigned to oral valganciclovir.
The researchers also report that: “The frequency and severity of adverse events were similar in the two treatment groups.” They go on to say that the main difference in safety between the two treatments was related to the mode of administration, with more diarrhoea in the oral valganciclovir group and more catheter-related complications in the intravenous group.
The study was not designed to evaluate the differences between the treatments for maintenance therapy, and the team say this would require a randomised comparison of patients followed up to the time of the progression of retinitis. However, they add: “On the basis of its efficacy for induction, and the pharmacokinetic data, we would expect valganciclovir to compare favourably with both intravenous and oral ganciclovir for maintenance therapy.”
They write that the reduced pill burden and once daily dosing with oral valganciclovir for maintenance treatment may increase adherence and therefore improve outcomes.
In their discussion, the researchers also comment: “Although there is no evidence on the basis of HIV loads and CD4+ cell counts, that highly active antiretroviral therapy affected our primary outcome at four weeks, it almost certainly influenced the observed times to progression of retinitis.”
The researchers end their discussion by advising: “Because of the heterogeneity of the immune response to highly active antiretroviral therapy, the time to the progression of retinitis may vary widely from patient to patient. Careful surveillance for progression of retinitis is therefore recommended throughout treatment.”
Well designed prophylaxis studies are now urgently needed to determine if oral valganciclovir is an effective agent for prevention as well as treatment of CMV retinitis.
Martin D. F., Sierra-Madero J., Walmsley S et al. A Controlled Trial of Valganciclovir as Induction Therapy for Cytomegalovirus Retinitis. N Engl J Med 2002; 346:1119-1126, Apr 11, 2002.