Clinical relevance of cytomegalovirus viraemia(*,†).
BACKGROUND
Using new sensitive quantitative polymerase chain reaction (PCR) assays, cytomegalovirus (CMV) DNA is often detectable in the plasma of immunosuppressed patients. We investigated the prognostic value of a positive CMV DNA test for the development of CMV end-organ disease, other AIDS-defining events and mortality.


METHODS
A survival analysis was performed, using the Kaplan-Meier method and Cox proportional hazards models, for patients prospectively followed in the Swiss HIV Cohort Study, from January 1996 to December 2007, who were CMV-seropositive, had a CD4 count of ≤ 100 cells/μL, and had a plasma sample available for the measurement of baseline CMV DNA with an ultrasensitive PCR. The outcome analysed was an AIDS-defining event, including CMV end-organ disease, or death. Variables analysed at the time of CMV measurement were demographic variables, CD4 cell counts, HIV-1 RNA loads, and use and type of highly active antiretroviral therapy (HAART).


RESULTS
Of 1128 patients, 208 (18%) presented an AIDS-defining event and 246 (22%) died. A total of 368 patients (34% of samples) had detectable CMV DNA at baseline, with DNA concentrations of up to 38 800 copies/mL. In the multivariate analysis, CMV DNA predicted evolution not only towards CMV end-organ disease [hazard ratio (HR) 12.6; 95% confidence interval (CI) 4.27-37.41], but also towards other AIDS-defining events (HR 2.6; 95% CI 1.60-4.33) and death (HR 1.9; 95% CI 1.10-3.34).


CONCLUSIONS
Quantitative CMV DNA detected in the plasma of HIV-infected patients with CD4 counts ≤ 100 cells/μL is a predictor for HIV disease progression, CMV disease and death. A single low value of 80 copies/mL identifies patients at low but significantly increased risk during the following months, after the measurement.
HIV Unit, Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland. emmanuelle.boffi@hcuge.ch
E Boffi
EB
El Amari
C
C
Combescure
S
S
Yerly
A
A
Calmy
L
L
Kaiser
B
B
Hasse
H
H
Furrer
M
M
Cavassini
P
P
Vernazza
Hh
H
Hirsch
E
E
Bernasconi
B
B
Hirschel
D017088:AIDS-Related Opportunistic Infections / Q000235:genetics* / Q000401:mortality / Q000821:virology; D000328:Adult; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000401:mortality / Q000821:virology; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000235:genetics* / Q000401:mortality / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013557:Switzerland / Q000453:epidemiology; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis / Q000235:genetics* / Q000821:virology
D004279:DNA, Viral