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CD4 count questioned as predictor of CMV activity
Continued anti-CMV retinitis therapy may not be necessary for some patients with stabilized disease.
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Recent research on cytomegalovirus retinitis conducted during the era of highly active antiretroviral therapy indicates that CD4 cell count may not be the most accurate predictor of CMV retinitis activity.
CMV retinitis was once expected to occur in up to 40% of patients with AIDS. However, since the introduction of HAART, remission and slower progression of CMV retinitis have been observed in these patients. CD4 cell counts have traditionally been indicative of an AIDS patient’s susceptibility to CMV retinitis activity.
Historically, patients have been considered at risk for developing CMV retinitis when their CD4 cell counts dropped below 50/µl. Since the introduction of HAART, the incidence of CMV disease has diminished dramatically as patients have been attaining immune reconstitution.
In the June issue of Retina, Mi-Kyoung Song, MD, et al reported on several AIDS patients in whom CMV retinitis activity seemed to operate independently of their CD4 cell counts. Dr. Song discussed one case that developed CMV retinitis despite immune reconstitution, while another four cases remained free of CMV retinitis despite HAART failure and CD4 cell counts below 50/µl.
Another study by Danny Y. Lin, MD, et al, also published in the June issue of Retina, concluded that the HIV viral load following HAART is a better clinical predictor of CMV retinitis activity. The report said that post-HAART CD4 cell levels were potentially the second-best clinical predictor when considered in combination with the post-HAART viral load.
Based on the minimum HIV viral load achieved after HAART, the authors said that it may now be possible to develop a strategy for predicting potential candidates for discontinuation of CMV retinitis therapy.
Atypical CMV activity
Dr. Song and colleagues conducted a prospective, longitudinal, observational study of 116 AIDS patients with CMV retinitis who were followed at the AIDS Ocular Research Unit of the University of California at San Diego. According to the report, 60 (52%) of the patients did respond to HAART; 44 of these patients were able to discontinue anti-CMV therapy.
During the follow-up, HAART failed for nine of the 44 patients, with CD4 cell counts dropping below 50/µl. However, reactivation of retinitis occurred in only five of these nine patients. The median CD4 cell count at the time of CMV reactivation for these patients was 41/µl. The researchers reported that the mean CD4 cell count for the remaining four patients without CMV reactivation was 11/µl.
“This clarifies that no arbitrary number of CD4 cells can be established as a cutoff value,” the authors said.
In addition, newly diagnosed CMV retinitis was detected in one patient who continued to receive HAART for a prolonged period and who had a CD4 cell count greater than 100/µl, they reported.
“The presence of active CMV retinitis in our patient with a sustained high CD4 cell count illustrates that an absolute CD4 cell count value may not be predictive of protection from CMV retinitis,” the authors said.
According to the researchers, one possible explanation for their findings is that the T-cells the researchers measured “may not be the direct agents of viral control and another immune mechanism is restricting viral replication.” Therefore, they said, it is not possible to draw conclusions regarding the correlation of lymphoproliferative response regarding the reactivation of CMV retinitis.
No predictive pattern was seen after comparing CD4 cell counts of those with reactivated CMV retinitis with those who remained free of CMV retinitis, the report said.
The authors recommend frequent observation of CMV retinitis patients to detect reactivation of the disease.
Retrospective review
Dr. Lin and colleagues from Stanford University, University of California San Francisco and Kaiser Permanente San Francisco noted in their report that no standard clinical criteria have been developed for the selective discontinuation of anti-CMV treatment. According to their report, this is important to provide clinicians with more precise information on the natural course of CMV retinitis in the HAART era.
Researchers conducted a retrospective analysis of the medical records of 53 HIV-infected patients and examined nine variables as potential predictors of a favorable CMV remission status. These included baseline CD4 cell count, post-HAART CD4 cell count, the absolute rise in CD4 cell count, baseline clinical weight, the absolute rise in clinical weight, the percentage of post-HAART weight improvement, log of baseline HIV viral load, log of minimum post-HAART viral load and log unit reduction in HIV viral load.
Study subjects were separated into two groups. Eighteen patients (26 eyes with CMV retinitis) were included in a non-HAART, matched historical control group and were compared to 35 patients (47 eyes with CMV retinitis) in a HAART-treated group.
Prolonged remission
According to the report by Lin et al, patients who did not receive HAART had a mean CMV retinitis remission of 80.5 days. This was compared with a mean CMV retinitis remission of 574 days for patients treated with HAART.
According to the report, the log of the minimum post-HAART viral load, when considered alone, was the only significant predictor of CMV retinitis progression or recurrence.
However, the authors said, “It is possible that additional data would show that CD4 change could usefully supplement post-HAART HIV viral load as a predictor of the course of CMV progression.”
Dr. Lin and colleagues wrote that within the HAART-treated group, similar patterns of patient remissions suggest the beneficial effect of HAART on CMV retinitis is long-lasting, extending beyond the first episode of CMV retinitis reactivation.
“Selected patients with stable CMV retinitis activity may not require continued anti-CMV therapy. Standardized clinical criteria are needed to identify this group of patients with CMV retinitis from those more likely to progress,” the authors wrote.
Nine variables
Most of the nine clinical variables that Dr. Lin and colleagues examined did have some degree of a positive correlation with the achievement of CMV retinitis remission. However, they said, the minimum HIV viral load achieved following HAART most closely correlated with prolonged CMV retinitis remission. Other variables demonstrated only a mild significance.
“This study suggests that the HIV viral load response is a better clinical predictor of a favorable remission,” the authors wrote. The rise in post-HAART CD4 levels was potentially the second best clinical predictor when used in combination with the minimum post-HAART viral load data.
According to the report, the results of the study suggest that immune recovery, as indicated by CD4 cell counts, may not be adequate predictors of continued CMV retinitis remission.
According to the report, based on the minimum HIV viral load achieved after HAART, it may now be possible to develop a strategy for predicting potential candidates for discontinuation of CMV retinitis therapy.
For your information:References:
- Mi-Kyoung Song, MD, can be reached at Eye Associates of New Mexico, 101 Hospital Loop NE, Albuquerque, NM 87109; (505) 883-6800; fax: (505) 889-3589; e-mail: mi_kyoungs@hotmail.com; Web site: www.eyeassociatesnm.com.
- Danny Y. Lin, MD, can be reached at the department of ophthalmology at Stanford University Medical Center, 900 Blake WIlbur Drive, Stanford, CA 94305; (650) 723-6995; (650) 723-7918.
- Song M, Schrier RD, et al. Paradoxical activity of CMV retinitis in patients receiving highly active antiretroviral therapy. Retina. 2002;22:262-267.
- Lin DY, Warren JF, et al. Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy in HIV-infected patients. Retina. 2002;22:268-277.