Cytomegalovirus polymerase chain reaction viraemia in patients receiving ganciclovir maintenance therapy for retinitis.
OBJECTIVE
To determine whether recurrence of polymerase chain reaction (PCR) viraemia during maintenance ganciclovir for cytomegalovirus (CMV) retinitis correlates with (i) CMV disease at a new anatomical site, (ii) progression of the presenting retinitis, or (iii) acquisition of genetic changes in gene UL97 associated with resistance to ganciclovir.


METHODS
A previously described cohort of 45 patients presenting with first episode retinitis was followed clinically using ophthalmoscopy and serial tests for PCR viraemia for a median of 7 months. CMV viral 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 episodes 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 after reinduction ganciclovir therapy compared with three out of four without markers of resistance (P=0.022).


CONCLUSIONS
CMV PCR viraemia correlated strongly with the development of new episodes of CMV disease. Most patients with progression of retinitis remained PCR-negative in blood, consistent with therapeutic failure due to poor intraocular penetration 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 management of patients with CMV disease are discussed.
Bowen
E F
EF
Department of Virology, Royal Free Hospital and School of Medicine, London, UK.
Emery
V C
VC
Wilson
P
P
Johnson
M A
MA
Davey
C C
CC
Sabin
C A
CA
Farmer
D
D
Griffiths
P D
PD
D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000235:genetics* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000821:virology; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000821:virology*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D004352:Drug Resistance, Microbial / Q000235:genetics; D015774:Ganciclovir / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D012008:Recurrence; D014759:Viral Envelope Proteins / Q000235:genetics; D014766:Viremia / Q000821:virology*
D000998:Antiviral Agents; D004279:DNA, Viral; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir