Consequences for the management of cytomegalovirus.

BACKGROUND

Recent advances in the field of antiretroviral therapy have led to a new era where it is possible to effectively prolong the survival of HIV-infected patients. However, a corollary is the increasing prevalence of opportunistic infections, such as cytomegalovirus (CMV). CMV disease is associated with substantial morbidity, mortality, moral prejudice, impaired quality of life and cost.

THE NATURAL HISTORY OF CMV INFECTION

The natural history of CMV infection consists of three phases: there is latent CMV infection with a low CMV viral load where, ideally, prophylactic treatment is indicated; then at the opposite end of the spectrum there is CMV visceral localization, associated with clinical symptoms and tissue injuries, where acute therapy is required. In between these two stages, there is reactivation of CMV, in the absence of clinical symptoms, characterized by a medium or high viral load. Early pre-emptive therapy is indicated at this stage. It is clearly very important to distinguish between these stages in order that the patient receives optimum therapy. PROPHYLAXIS AND PRE-EMPTIVE THERAPY: A recent large, placebo-controlled study has revealed the prophylactic efficacy of oral ganciclovir, with a significant reduction in the incidence of CMV disease after both 12 and 18 months. The fact that patients in this study who had reactivation of CMV virus experienced more limited benefits than those who did not have reactivation leads directly to the idea of pre-emptive therapy in those patients who are at high risk of developing the disease. Drugs used for pre-emptive therapy include foscarnet, ganciclovir and cidofovir; oral adefovir and lobucavir are also currently in development.

CONCLUSIONS

The understanding of CMV infection and disease is entering a new phase. However, new drugs and new therapeutic regimens need to be evaluated and there is an urgent need for techniques to evaluate virological markers of infection and the efficacy of treatment.