CYTOMEGALOVIRUS POLYMERASE-CHAIN-REACTION VIREMIA IN PATIENTS RECEIVING GANCICLOVIR MAINTENANCE THERAPY FOR RETINITIS

Objectives: To determine whether recurrence of polymerase chain reacti on (PCR) viraemia during maintenance ganciclovir for cytomegalovirus ( CMV) retinitis correlates with (i) CMV disease at a new anatomical sit e, (ii) progression of the presenting retinitis, or (iii) acquisition of genetic changes in gene UL97 associated with resistance to ganciclo vir. Design: A previously described cohort of 45 patients presenting w ith first episode retinitis was followed clinically using ophthalmosco py and serial tests for PCR viraemia for a median of 7 months. CMV vir al load and genetic markers of ganciclovir resistance were measured in PCR-positive samples. Methods: PCR amplification of the glycoprotein B region of CMV and quantitative competitive PCR assays were employed. Genetic changes in UL97 were identified by sequencing/point mutation assay. Results: PCR viraemia correlated significantly with new episode s of CMV disease (P = 0.011) and a trend was seen for the association with progression of retinitis (P = 0.07). Amongst the 14 patients PCR- positive during maintenance ganciclovir, 10 (71%) had genetic markers of resistance. None of these patients became PCR-negative in blood aft er reinduction ganciclovir therapy compared with three out of four wit hout markers of resistance (P = 0.022). Conclusions: CMV PCR viraemia correlated strongly with the development of new episodes of CMV diseas e. Most patients with progression of retinitis remained PCR-negative i n blood, consistent with therapeutic failure due to poor intraocular p enetration of ganciclovir. However, the minority who were PCR-positive in blood may have reinfected their eye, and frequently had markers of ganciclovir resistance. The implications of these findings for the ma nagement of patients with CMV disease are discussed. (C) 1998 Lippinco tt-Raven Publishers.