Importance of cytomegalovirus viraemia in risk of disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy

Lancet. 2004 Jun 26;363(9427):2116-21. doi: 10.1016/S0140-6736(04)16500-8.


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.

Findings: 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).

Interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / virology*
  • Acquired Immunodeficiency Syndrome / diagnosis
  • Acquired Immunodeficiency Syndrome / virology
  • Adult
  • Aged
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / complications*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / virology
  • DNA, Viral / blood
  • Disease Progression
  • Female
  • HIV / isolation & purification
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / mortality
  • HIV Infections / virology*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Proportional Hazards Models
  • RNA, Viral / blood
  • Risk Factors
  • Viremia* / diagnosis
  • Viremia* / physiopathology


  • DNA, Viral
  • RNA, Viral