HIV patients who were previously vaccinated against smallpox lose their immunity, according to a recent study.

An article in the Journal of Infectious Diseases points out why that occurs even after HIV patients have had much of their immune system restored with antiretroviral therapy.

Oregon Health and Science University–led researchers said that HIV-associated immune amnesia could help explain why HIV patients tend to have higher mortality rates than HIV-negative counterparts despite being on antiretroviral therapy. 

Smallpox immunity was chosen for measurement because its last known U.S. case was in 1949; researchers knew that study subjects hadn't recently been exposed to its virus, which would have triggered new T-cell and antibody responses.

The study team notes that it has remained unclear whether HIV infection results in permanent loss of T-cell memory or whether it impacts preexisting antibodies to previous vaccinations/infections. To help resolve that issue, researchers conducted a matched cohort study involving 50 pairs of women who were HIV-positive and HIV-negative.

To do that, they measured total memory T-cell responses after anti-CD3 stimulation or after vaccinia virus stimulation to measure T cells elicited after earlier smallpox vaccination. 

Results indicated no difference between HIV-positive and HIV-negative participants in terms of CD4+ T cell responses after anti-CD3 stimulation (P = .19), although HIV positive subjects had significantly higher CD8+ T-cell responses (P = .033). 

“In contrast, there was a significant loss in vaccinia-specific CD4+ T cell memory among HIV+ subjects (P=0.039) whereas antiviral CD8+ T cell memory remained intact (P=1.0),” the authors wrote. “Vaccinia-specific antibodies were maintained indefinitely among HIV- subjects (half-life; infinity, 95%CI, 309 years-infinity) but declined rapidly among HIV+ subjects (half-life; 39 years, 95%CI, 24-108 years, P=0.001).”

Antiretroviral therapy did not change the situation, according to the researchers, who added, “Despite ART-associated improvement in CD4+ T cell counts (nadir CD4 <200 cells/mm3 with >350 cells/mm3 after ART), antigen-specific CD4+ T cell memory to vaccinations/infections that occurred before HIV infection did not recover after immune reconstitution and a previously unrealized decline in pre-existing antibody responses was observed.”

The authors explain that, in normal situations, people vaccinated against smallpox have CD4 T cells that remember the virus and respond in large numbers when they are exposed. In fact, they point out, previous research has shown that smallpox virus–specific CD4 T cells are maintained for up to 75 years after vaccination.

Future research will look at the effect in HIV-infected men and at whether HIV patients also lose immune memory to other diseases for which they have received vaccines.

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