Plasma cytomegalovirus DNA, pp65 antigenaemia and a low CD4 cell count remain risk factors for cytomegalovirus disease in patients receiving highly active antiretroviral therapy.
OBJECTIVE
To study the natural history and the current risk factors for cytomegalovirus (CMV) disease in the context of highly active antiretroviral therapy (HAART).


METHODS
Prospective multicentre cohort in 15 university hospitals in France.


METHODS
A group of 198 patients with CD4 cell count < 100 x 10(6) cells/l (or < 200 x 10(6) cells/l under HAART for at least 2 months), no previous CMV disease and CMV-positive serology were followed every 4 months clinically and for virological testing including HIV RNA and CMV blood markers (culture, pp65 antigenaemia, plasma CMV DNA and CMV late mRNA by the polymerase chain reaction).


RESULTS
At inclusion, median CD4 was 77 x 10(6) cells/l (0-308) and 85% of the patients received protease inhibitors. The percentage of patients receiving HAART reached 99% at 12 months. After a follow-up of 23.6 months, the incidence of CMV disease was 3.2/100 patient-years [95% confidence interval (CI) 1.3-5.0]. In univariate Cox models, all the CMV markers, a CD4 cell count remaining < 75 x 10(6) cells/l and an HIV viral load > 100,000 copies/ml were predictive for CMV disease. The hazard ratios for CMV disease were 11 for blood culture; 14 and 70 for pp65 antigenaemia of > or = 1 and > or = 100 nuclei/200,000 cells, respectively; 35 for plasma CMV DNA; 6 for CMV mRNA; 29 for CD4 < 75 x 10(6) cells/l; and 12 for HIV RNA > 100,000 copies/ml. In a stepwise multivariate analysis, only three covariates were independently associated with the occurrence of a disease: plasma CMV DNA, pp65 antigenaemia > or = 100 nuclei/200,000 cells and a CD4 count < 75 x 10(6) cells/l.


CONCLUSIONS
CMV blood markers and CD4 count < 75 x 10(6) cells/l remain risk factors for CMV disease in patients receiving HAART. Analysis of plasma CMV DNA by the polymerase chain reaction is a reproducible and standardized tool that could be used as a decision marker for initiating CMV pre-emptive therapy.
Salmon-Céron
D
D
Department of Internal Medicine, Hospital Cochin, Paris, France.
Mazeron
M C
MC
Chaput
S
S
Boukli
N
N
Senechal
B
B
Houhou
N
N
Katlama
C
C
Matheron
S
S
Fillet
A M
AM
Gozlan
J
J
Leport
C
C
Jeantils
V
V
Freymuth
F
F
Costagliola
D
D
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000821:virology; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000097:blood*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D010750:Phosphoproteins; D018894:Reverse Transcriptase Inhibitors; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa