High cytomegalovirus antigenemia levels and cytomegalovirus syndrome in patients with AIDS.

Abstract

To the Editor: Two recent studies published in this journal showed that quantitative cytomegalovirus (CMV) antigenemia assay is a rapid and simple test that could be used to identify patients with clinical disease, but there is no sensible cutoff to differentiate CMV disease and other states of CMV replication(1,2). Up to 50% of AIDS patients have periods of CMV viremia together with other opportunistic infections(3). Our own experience is similar. However, although no strict individual correlation could be observed between levels of antigenemia and disease manifestations, previous studies have found higher levels of viremia in patients with symptomatic CMV infection than in asymptomatic patients(4). Over an 18-month period, we have prospectively studied 230 HIV-infected patients with a CD4+ cell count <100/mm3 to establish the significance of high CMV antigenemia levels. Quantitative CMV antigenemia tests were performed with CMV monoclonal antibodies against CMV lower matrix protein pp65 (Argene Biosoft, Varilhes, France). Results were expressed as the number of positive cells per 200,000 peripheral blood leukocytes (PBL). We defined high antigenemia levels as those values > 125 positive cells/2 x 105 PBL, because this was the highest value found in our population of asymptomatic HIV patients at the same level of immunodepression. During this period, 18 patients (8%) presented higher CMV antigenemia levels than the above mentioned value. In 13 cases, a definitive diagnosis of CMV disease was achieved: retinitis in 7 cases, colitis in 4, esophagitis in 1, and encephalitis in 1. Strikingly, the remaining 5 patients presented a clinical feature characterized by mild pneumonitis, hepatitis, and bone marrow suppression, usually neutropenia. Three had concomitant fever. Specific studies failed to identify either focal CMV disease or the presence of other opportunistic pathogens. A median value of 965 positive cells/2 x 105 PBL (range, 214-1500 positive cells/2 x 105 PBL) was found in these 5 cases. We observed a complete clinical and biochemical response and disappearance of antigenemia after treatment with ganciclovir (in 3 cases) or foscarnet (in 2 cases). However, 2 patients developed CMV retinitis in a 3-month period and all patients died before 4 months of follow-up. We have prospectively observed a cohort of AIDS patients to investigate the importance of high levels in the CMV antigenemia test. These results show that patients with high CMV antigenemia levels had focal or disseminated CMV disease, and these values were associated with a shorter time to progression and death. Although it is likely to find CMV viremia in otherwise asymptomatic HIV individuals with severe immunodepression, we have never observed levels as high as those seen in the 5 cases described above. Thus, the positive predictive value of CMV disease for high CMV antigenemia levels was 100% in our study, reflecting a correlation between a high grade of viremia and disease. This fact correlated with the effect described with high CMV load, as measured by quantitative-competitive polymerase chain reaction (PCR), on progression and survival(5). Characteristically, we failed to demonstrate focal CMV disease in 5 patients despite the high CMV antigenemia levels. This CMV syndrome presented with fever, mild lung disease, hepatitis, and neutropenia, similar to that described in transplant recipients(6). Although most clinical articles about CMV in AIDS include as disseminated disease the involvement of two or more organs, we believe that our patients probably represented a defined pattern of CMV disease. This CMV syndrome may be not previously well defined in AIDS patients because of the higher frequency of at least one affected organ or the short survival of very immunosupressed AIDS patients. The main diagnostic tool in the cases described was the result of quantitative CMV antigenemia assay. We found significantly higher values in these 5 patients in comparison with asymptomatic patients, and even in those with CMV retinitis or colitis. Therefore, in our experience, high levels of CMV antigenemia were strongly correlated with either focal or disseminated CMV disease. Pending further studies, early institution of antiviral therapy should be considered in these cases. Lucía G. San Miguel José L. Casado Angelina Ca~nizares Mercedes Lobo Antonio Guerrero Department of Infectious Diseases; Hospital Ramón y Cajal; Madrid, Spain