Ganciclovir is associated with low or undetectable Epstein-Barr virus DNA load in cerebrospinal fluid of patients with HIV-related primary central nervous system lymphoma.
BACKGROUND
Epstein-Barr virus (EBV) is pathogenically linked to human immunodeficiency virus (HIV)-related primary central nervous system lymphoma (PCNSL) and is found in virtually all HIV-related PCNSL cases. The objective of this study was to assess the effect of ganciclovir on EBV DNA replication in patients with HIV-related PCNSL.


METHODS
EBV DNA was measured by real-time polymerase chain reaction in cerebrospinal fluid and plasma samples from 25 patients with HIV-related PCNSL. Eight of these patients were receiving ganciclovir for concurrent cytomegalovirus infections.


RESULTS
EBV DNA was detected in cerebrospinal fluid samples obtained from 15 (88%) of 17 ganciclovir-untreated patients and 4 (50%) of 8 ganciclovir-treated patients (P = .028). EBV DNA load was significantly lower for treated patients, compared with untreated patients (median value, 2.15 vs. 4.16 log copies/mL; P = .001). Analysis of sequential cerebrospinal fluid samples from 7 patients showed that EBV DNA decreased in samples obtained from 2 patients following the start of ganciclovir administration but did not decrease in samples obtained from the 5 untreated patients. In addition, patients who received ganciclovir survived longer than the untreated patients (median duration of survival, 181 vs. 72 days; P = .006).


CONCLUSIONS
The effect of ganciclovir on EBV DNA load in cerebrospinal fluid supports the hypothesis that EBV is replicating in patients with PCNSL. This observation, together with the effect of ganciclovir therapy on patient survival, suggests that this drug might be useful for the management of PCNSL.
Bossolasco
Simona
S
Clinic of Infectious Diseases, San Raffaele Hospital, Milan, Italy. bossolasco.simona@hsr.it
Falk
Kerstin I
KI
Ponzoni
Maurilio
M
Ceserani
Norberto
N
Crippa
Fulvio
F
Lazzarin
Adriano
A
Linde
Annika
A
Cinque
Paola
P
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications / Q000821:virology*; D003131:Combined Modality Therapy; D003586:Cytomegalovirus Infections / Q000150:complications / Q000188:drug therapy; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D020031:Epstein-Barr Virus Infections / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy*; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology* / Q000627:therapeutic use; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D015774:Ganciclovir