ART may not be completely effective in restoring immune protection, study suggests

A study led by researchers from SUNY Downstate Health Sciences University and Oregon Health & Science University, published in the Journal of Infectious Diseases, showed that, despite successful antiretroviral therapy (ART), antigen specific memory to vaccinations that occurred before HIV infection did not recover, even after immune reconstitution. Additionally, a previously unrealized decline in pre-existing antibody response was also observed.

Approximately two-thirds of HIV-positive patients in the U.S. are on an ART regimen. It works by reducing viral replication and boosting CD4 T cell counts, which are important to suppressing or regulating the immune response. Normally, these cells "remember" viruses and respond in large numbers when exposed again.

However, this study suggests that this memory is inhibited in some HIV-positive patients who are otherwise doing well on therapy. Should this loss of serological memory, or HIV-immune associated amnesia, exist for other pre-infection vaccinations or viruses, it would have significant implications for the overall health status of HIV patients, including:

• Providing an explanation for chronic inflammation and "accelerated aging" observed among people with HIV
• Suggesting a loss of protective immunity and an increased risk for common acute or chronic viral infections among people with HIV, regardless of whether they are on an ART regimen
• Suggesting a potential loss of protection against such common childhood diseases such as measles, mumps, chickenpox, pertussis (whooping cough) and others, for which these patients were previously vaccinated as children, prior to HIV infection, and not restored by ART

There is no doubt that ART provides significant, life-changing benefits for people with HIV by reconstituting their overall immune response. What our study suggests is that ART may not be completely effective in restoring the immune protection resulting from viral infections or childhood vaccines received prior to becoming HIV positive. This makes these patients potentially susceptible not only to these serious diseases, but also other chronic infections and to chronic inflammation that may diminish their overall health and shorten their lifespan."

Michael Augenbraun, MD, FACP. FIDSA, Professor of Medicine and Vice Chair, Department of Medicine and Director, Division of Infectious Diseases at SUNY Downstate Health Sciences University and Kings County Hospital Center

Dr. Augenbraun cautions that, while this study only examined immunologic responses to smallpox vaccination and not to specific clinical outcomes, it builds on previous studies and evidence pointing to HIV-associated immune amnesia. He says additional studies need to be conducted both on HIV positive men utilizing the smallpox vaccine antigen, and antigens of other common diseases for which people are vaccinated as children. Additionally, Dr. Augenbraun believes the study may also contribute to gathering support for earlier aggressive treatment in HIV infected individuals before they suffer significant damage to their immune system.

Should future studies identify broader HIV-associated immune amnesia, it could mean that a significant proportion of the 1.1 million people in the U.S. and more than 23 million people worldwide living with HIV have diminished protection from previous immunizations. However, he cautioned that the potential need for revaccination of patients, although suggested by these data, was not directly addressed by the study.