Applying lessons of immune response to CMV retinitis, AIDS

May 2, 2016

Modern combination antiretroviral therapy (cART) has transformed the AIDS epidemic and the management of cytomegalovirus (CMV) retinitis.

Seattle-Modern combination antiretroviral therapy (cART) has transformed the AIDS epidemic and the management of cytomegalovirus (CMV) retinitis, said Douglas A. Jabs, MD, MBA.

Speaking at ARVO 2016, Dr. Jabs outlined the pathogenic mechanisms of CMV retinitis, reviewed clinical predictions based on understanding of the pathophysiology, and presented clinical data corroborating those predictions.

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The information demonstrated interactions between CMV and HIV and the importance of the immune response in controlling CMV disease, said Dr. Jabs, professor and chairman of ophthalmology, Mount Sinai School of Medicine, New York.

Discussing the variety of mechanisms CMV uses for immune evasion and to establish latent infection, Dr. Jabs said that the virus interferes with class I expression and antigen presentation to CD8+ T cells. It also produces a class I homolog on the surface of infected cells so that it avoids natural killer (NK) cell clearance.

In addition, the virus produces an IL-10 homolog binding to the human IL-10 receptor and downregulates Th1 responses.

Key facts

 

Dr. Jabs explained how this information, together with knowledge of interactions that occur between CMV and HIV (HIV selectively depletes CD4+ T cells and the two viruses transactivate each other) account for a number of facts:

·      CMV retinitis occurs most often in the context of AIDS rather than in persons with other causes of immunosuppression;

·      persons with a polymorphism in the IL-10 receptor are protected against the development of CMV retinitis;

·      CMV co-infection accelerates HIV disease;

·      effective treatment of CMV lowers the HIV load in peripheral blood; development of CMV resistance to antiviral treatments correlates with increased HIV-related mortality;

·      local ocular treatment of CMV retinitis in one eye does not prevent infection in the fellow eye; and

·      systemic anti-CMV therapy during the period of immunocompromise reduces the likelihood of second eye CMV involvement, new visceral CMV disease, and mortality in patients with AIDS.

In addition, Dr. Jabs presented data showing how modern cART-which provides sustained suppression of HIV replication and allows immune recovery as manifested by a rise in CD4+ T cells-has been associated with a >90% decline in CMV retinitis and decrease in mortality.

Transformation of AIDS

 

“Indeed, immune recovery controls CMV replication and permits discontinuation of specific anti-CMV treatment,” Dr. Jabs said.

He concluded by talking about what he termed “the real transformation” of AIDS, referring to data from the Studies of the Ocular Complications of AIDS Research Group showing that with the advent of modern cART, patients who develop CMV retinitis and achieve immune recovery now enjoy an almost-normal lifespan.

“Prior to the advent of modern cART, patients who developed CMV retinitis had a median survival of just 1 year,” he said. “We found that today, the median survival for AIDS patients who develop CMV retinitis but fail to achieve immune recovery is the same, just 13 months. However, for those who do get immune recovery, their median survival was estimated to be 27 years.”