Pre-emptive CMV therapy should be prescribed for HIV-infected individuals on antiretroviral therapy who have a CD4 count below 75 and blood markers of CMV reactivation, according to French researchers.
The group led by Dr Dominique Salmon-Céron of the Hospital Cochin made the recommendation based on a study of 198 individuals with advanced HIV disease who were followed for two years.
Eleven individuals developed CMV disease during follow-up, most within 10 months of commencing HAART. The study found that individuals who had not sustained immune recovery above 75, and had signs of CMV antigen or virus in their blood were the group most at risk of CMV disease. Specifically, a positive plasma CMV DNA result, a pp65 antigenaemia greater than 100 nuclei/200,000 cells and a CD4 count below 75 were significantly associated with a greater risk of CMV disease. However, due to the low number of CMV cases, the authors warned that the results should be treated with caution.
Risk of CMV disease was reduced by immune recovery rather than viral suppression. The average CD4 count when CMV diagnosis occurred was 13, although 3 individuals had counts above 50, including one with a count of 160. Disappearance of CMV markers was associated with a CD4 count that rose above 75.
The French study confirmed findings by several other teams linking CMV markers with risk of CMV disease. For example, a study at London's Royal Free Hospital found that among people with CD4 counts below 50, those who developed CMV DNA viraemia were seven times more likely to develop CMV disease than those with no DNA viraemia (Bowen).
Should screening be introduced?
In the UK, primary prophylaxis for CMV disease is not routine practice. However, these studies identified those individuals most at risk of CMV disease, which would facilitate well-targetted prophylaxis.
A key problem with CMV screening has been that CMV DNA only appears about two months before disease, and the expense of such regular screening is unlikely to be cost effective. Another problem with DNA screening is that many people with immune recovery have a positive CMV DNA result but do not develop disease, probably due to immune restoration. At this stage, CMV DNA testing is not practical or effective.
The French group recommended the CMV antigen test, which is an earlier and highly accurate predictor of CMV disease, should be used to screen for CMV until a more sensitive DNA test is developed. However, the antigen test also requires rapid processing and considerable labour, so whether this approach to screening will be adopted in the UK remains to be determined.
At the Royal Free Hospital in London, Dr Jane Deayton says that screening for CMV viremia is routine practice, and that in the past few months several patients have resumed or started CMV prophylaxis as a result of a declining CD4 count and resurgent CMV activity.
"We're looking at doing a study or audit protocol of pre-emptive therapy in this group of patients, since we are suddenly starting to see cases of CMV after a period of 18 months with no cases", she told aidsmap.
"The CD4 count can give a general idea of the risk of CMV but becoming viremic substantially increases the risk, and testing for CMV viremia allows us to target prophylaxis and spare people the risk of toxicity".
References
Bowen EF et al. Cytomegalovirus (CMV) viraemia detected by polymerase chain reaction identifies a group of HIV-positive patients at high risk of CMV disease. AIDS 11(7):889-893, 1997.
Bowen EF et al. Cytomegalovirus polymerase chain reaction viraemia in patients receiving ganciclovir maintenance therapy for retinitis. AIDS 12(6):605-611, 1998.
Chevret S et al. Usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death in patients with AIDS. Clinical Infectious Diseases 28(4):758-763, 1999.
Salmon-Ceron D et al. Plasma cytomegalovirus DNA, pp65 antigenaemia and a low CD4 cells count remain risk factors for cytomegalovirus disease in patients receiving highly active antiretroviral therapy. AIDS 2000 14(8):1041-1049