Review
Cytomegalovirus disease in the era of highly active antiretroviral therapy (HAART)

https://doi.org/10.1016/j.jcv.2006.03.005Get rights and content

Abstract

Cytomegalovirus (CMV) infection was one of the most important opportunistic infections in HIV-infected patients before the introduction of highly active antiretroviral therapy (HAART), i.e. the combination of at least three antiretroviral drugs of different classes. Thereafter, life expectancy and quality of life increased dramatically with the persistent suppression of HIV viremia and a significant reduction in incidence of CMV disease. Nevertheless, evidence for a multitude of direct and indirect effects of CMV on HIV progression is accumulating. Even in the era of HAART, a considerable number of HIV-infected patients have a CD4 cell count below <100 mm−3, which involves a high risk for CMV disease. The focus of the present review is on interpretation of test results, their predictive value for CMV disease, and guidance for the rational use of diagnostic assays in HIV-infected patients. Identification of patients at immediate risk for CMV disease may be accomplished by detection of CMV-DNA in leucocytes or plasma. Evidence is growing that CMV genotypes may be also relevant for the risk of CMV disease. Diagnosis of CMV disease requires in most instances demonstration of virus in biopsy specimen from the affected organ because presence of CMV in blood may not be causally related to symptoms observed. Clinical symptoms and patient characteristics are essential in the interpretation of laboratory test results and may guide the rational collection of clinical specimen and use of laboratory assays. As a consequence, a reliable diagnosis of CMV disease and early identification of patients at high risk for CMV disease requires an integrated interpretation of clinical and virological information.

Section snippets

Changing epidemiology of CMV disease

Cytomegalovirus (CMV) infection was one of the most important opportunistic infections in HIV-infected patients before the introduction of HAART. Approximately 40% of HIV-infected patients with advanced disease suffered from one of several different manifestations of CMV disease during life-time (Bowen et al., 1996, Jabs et al., 1989, Pertel et al., 1992, Drew, 1992). Prophylaxis and treatment of other AIDS-related opportunistic infections had improved overall prognosis and extended

Is CMV still an issue?

Given this dramatic drop in incidence of CMV disease in HIV-infected patients, is it reasonable to worry about this infection anymore? Considering the evidence for a multitude of direct and indirect effects of CMV on HIV progression, the answer has to be yes. CMV-seropositive individuals progress 2.5 times more rapidly to AIDS and death than those who are CMV seronegative (Webster et al., 1989, Sabin et al., 2000, Sabin et al., 1995). In the case of primary CMV infection, even patients with

Virological diagnosis of disease

A large variety of laboratory techniques is available for the rapid and reliable diagnosis of CMV infection and disease. The individual assays have been reviewed in detail previously in this Journal (Grangeot-Keros and Cointe, 2001, Baldanti et al., 1998, de la Hoz et al., 2002). The focus of the following review will be on interpretation of test results, their predictive value for CMV disease, and guidance for the rational use of diagnostic assays in HIV-infected patients.

Clinical manifestations of CMV disease

Signs and symptoms are pathognomonic in a minority of manifestations of CMV disease. More commonly, clinical manifestations of CMV disease are too uncharacteristic to establish or refute the diagnosis of CMV disease. However, they may guide the rational use of virological assays and collection of clinical specimen.

Conclusions

Treatment of HIV-infected patients with HAART reduced dramatically the incidence of CMV disease, extended life expectancy and improved quality of life. Still, a considerable number of patients has CD4 cell counts below the critical threshold of 100 mm−3 and is therefore at high risk for CMV disease. All the more, early and reliable identification of patients at risk for and diagnosis of CMV disease remains critical in the management of HIV-infected patients. For this purpose, an integrated

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