Importance of cytomegalovirus viraemia in risk of disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy.
BACKGROUND
Before highly active antiretroviral therapy (HAART) became available, cytomegalovirus was a major cause of opportunistic infection in HIV-infected patients and was associated with accelerated progression to AIDS and death. We have investigated whether cytomegalovirus viraemia remains a significant risk factor for progression of HIV disease and death in the era of HAART.


METHODS
374 patients whose CD4-cell count had ever been below 100 per microL were enrolled in a prospective study. Serial blood samples were tested for cytomegalovirus by PCR. Rates of new cytomegalovirus disease, new AIDS-defining disorders, and death were calculated over a median follow-up of 37 months after stratification according to baseline and most recent cytomegalovirus PCR status at any point during follow-up.


RESULTS
Of 2969 PCR assays, 375 (12.6%) were positive for cytomegalovirus DNA. 259 (69.3%) patients were persistently negative for cytomegalovirus by PCR; 15 were persistently positive; and 100 were intermittently positive and negative. In multivariate models, cytomegalovirus PCR-positive status as a time-updated covariate was significantly associated with increased relative rates of progression to a new AIDS-defining disorder (2.22 [95% CI 1.27-3.88] p=0.005) and death (4.14 [1.97-8.70] p=0.0002).


CONCLUSIONS
Detection of cytomegalovirus in blood by PCR continues to identify patients with a poor prognosis, even in the era of HAART. Randomised controlled clinical trials of drugs active against cytomegalovirus are needed to investigate whether this virus is a marker or a determinant of HIV disease progression.
Deayton
Jane R
JR
Department of Virology, Royal Free and University College Medical School of University College London, Royal Free Campus, London, UK.
Prof Sabin
Caroline A
CA
Johnson
Margaret A
MA
Emery
Vincent C
VC
Wilson
Pauline
P
Griffiths
Paul D
PD
D017088:AIDS-Related Opportunistic Infections / Q000821:virology*; D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000821:virology; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000175:diagnosis / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D014766:Viremia / Q000175:diagnosis / Q000503:physiopathology
D004279:DNA, Viral; D012367:RNA, Viral