Anti-cytomegalovirus therapy may not be needed upon immune recovery

The recommendation that patients with AIDS and cytomegalovirus retinitis who attain immune restoration can discontinue their ocular therapy may be clinically justifiable.

Janet T. Holbrook

A study supported United States Public Health Service guidelines stating that anti-cytomegalovirus therapy may be discontinued after immune recovery in patients with AIDS.

“The take-home message is that the guidelines are sound and that, even if you look at things that are not surrogate measures but are clinical outcomes, patients who experience immune recovery and are taken off therapy for their CMV can do well,” Janet T. Holbrook, PhD, MPH, first study author, told Ocular Surgery News.

The analysis included a cohort of patients with cytomegalovirus (CMV) retinitis from the Longitudinal Study of Ocular Complications of AIDS, a prospective, observational study aimed at collecting data on the incidence, prevalence and complications resulting from AIDS-induced ocular morbidities since the introduction of highly active anti-retroviral therapy (HAART).

The study, published in the American Journal of Ophthalmology, supported prior findings but included vision and mortality outcomes not included in previous reports.

“I think we just have stronger data than previously published, because we compared prospective follow-up of patients who discontinued treatment and people who continued treatment, and it was in the context of a cohort study, so we had standardized methods for assessing CMV retinitis, including fundus photographs, as well as a larger group of patients,” Dr. Holbrook said.

CMV susceptibility, methods

CMV disease is more common in neonates, individuals who undergo transplant and patients with HIV disease because these individuals have a weakened immune system, according to Dr. Holbrook.

“Many of us are infected with CMV, probably 50% of the population, but most do not have a problem with CMV because we have a functioning immune system,” she said.

In this study, participants with CD4+ T-cell counts of 50 cells/µL or fewer who showed sustained immune recovery were categorized into two groups: those who continued anti-CMV treatment after immune recovery and those who did not. The factors most strongly associated with continued treatment were lower T-cell count, shorter time since CMV diagnosis and female gender.

Survival, progression of retinitis, incidence of bilateral retinitis and visual acuity were evaluated.

Results, ongoing follow-up

Of the 152 patients observed, 71 experienced immune recovery; 34 of the 71 continued therapy and 37 did not. No statistical difference was shown between the two groups for any outcomes assessed. Patients lost on average 1.2 letters of visual acuity per year regardless of treatment strategy (P < .01).

“The steady loss of acuity may indicate that despite control of CMV retinitis, these patients may be at higher risk than other AIDS patients or the general public for significant vision loss over their lifetimes,” the study authors wrote.

Considering such visual decline, as well as the potential for opportunistic infection, Dr. Holbrook and her research team continue to follow the cohort. Moreover, 5-year outcomes from the Longitudinal Study of Ocular Complications of AIDS, published in 2010, concluded that HAART does not terminate the increased risk for mortality, retinitis progression, retinitis complications and vision loss associated with CMV retinitis.

“[The risk] has not gone to zero. People still have retinitis progression, even if they have immune recovery, but it is a much lower risk. So we will be continuing to follow these patients over 10 years and longer,” Dr. Holbrook said.

She noted that the current study had a small sample size and an observational design, introducing selection bias, and thus did not provide definitive evidence. However, the data add to already accumulating support for the safety of discontinued treatment. – by Michelle Pagnani

References:

Holbrook JT, Colvin R, Van Natta ML, et al. Evaluation of the United States public health service guidelines for discontinuation of anticytomegalovirus therapy after immune recovery in patients with cytomegalovirus retinitis. Am J Ophthalmol. 2011;152(4): 628-637.

Jabs DA, Ahuja A, Van Natta M, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: five-year outcomes. Ophthalmology. 2010;117(11):2152-2161.

Janet T. Holbrook, PhD, MPH, can be reached at Johns Hopkins Center for Clinical Trials, 911 South Ann St., Baltimore, MD 21231; 443-287-5791; fax: 775-871-4030; email: jholbroo@jhsph.edu.

Disclosure: Dr. Holbrook has no relevant financial disclosures.

Since the introduction of HAART, patients with HIV and CMV retinitis are more likely to live longer as their CD4 count increases and viral load decreases. In 1999, the United States Public Health Service published recommendations to discontinue anti-CMV therapy in those with immune recovery and inactive retinitis. These recommendations were based on case series indicating a low risk for retinitis recurrence upon immune recovery. The paper analyzed data from the multi-centered Longitudinal Study of Ocular Complications of AIDS, highlighting that patients with sustained immune recovery who discontinued anti-CMV therapy had similar visual outcomes to those with recovery who continued therapy. However, both groups experienced some vision loss, supporting the need for continued observation. Clinicians can use the information from this study to inform recovered patients that discontinuing anti-viral therapy does not increase risk of vision loss or mortality.

– Sunil K. Srivastava, MD
Staff Physician, Cole Eye Institute
Disclosure: Dr. Srivastava receives research support from Allergan, Bausch + Lomb and Novartis. He was also a previous site principal investigator for the L-SOCA study.