Why Do People With HIV Lose Smallpox Immunity Despite Vaccination?

One of the concerns of living with HIV is the potential loss of immunity to certain diseases over time. For example, it’s been established that people with HIV suffer disproportionately from shingles, which is caused by the varicella-zoster virus. This virus also causes chickenpox, another ailment that can manifest particularly severely in people with HIV. This vulnerability to infection occurs even though antiretroviral therapy (ART) bolsters the immune system.

To delve into this issue, a team of investigators based at the Oregon Health & Science University School of Medicine’s Oregon National Primate Research Center and SUNY Downstate Medical Center in Brooklyn conducted a study, published in The Journal of Infectious Diseases, in which subjects’ blood was exposed to the vaccina virus, which is used to inoculate against smallpox. The study was comprised of 50 matched pairs of women, each with 1 woman who was HIV positive and 1 who was HIV negative. All had been born before 1971 and were vaccinated against smallpox. Smallpox was chosen for this study because it’s been more than 70 years since the last known case in the United States, so there was no danger of the women having been exposed to the virus in recent years.

The team discovered that the HIV-positive women had a much weaker immune response to the vaccina virus than their HIV-negative counterparts: Twenty percent of the HIV-negative subjects exhibited a CD4 T-cell response above the set detection threshold of at least 20 per 10⁶ CD4 T cells, but just 2.4% of the subjects with HIV had a similar detectable response.

The study’s authors say the results show that even though ART reconstitutes the immune response of a person with ART, this reconstitution may not hold for certain viruses or vaccines that person had in childhood. “They lost that immune memory somewhere,” Michael Augenbraun, MD, director of the Division of Infectious Diseases at SUNY Downstate Medical Center and an author of the study, told Contagion®, referring to the HIV-positive subjects in the trial. “Our hunch is that there’s some damage there that’s just not fixable.”

The study’s HIV-positive subjects also displayed an increased CD8 T cell response, which the investigators believe contributes to a heightened inflammatory state that may cause long-term health problems. “[This loss of immunity] allows for chronic inflammation and the accelerated aging that we see in HIV patients,” Augenbraun said.

Revaccinating an HIV-positive person against infectious agents is unlikely to provide a solution, according to Augenbraun. “We don’t really know what the clinical risk is in these people who have lost their immunity,” he said, adding that an already-damaged immune system might not respond to another dose of immunization.

While smallpox was the only vaccine studied in the current trial, Augenbraun said more research will be undertaken to explore the likelihood that people living with HIV have reduced immunity to other conditions as well. “Measles comes to mind, mumps comes to mind, pertussis comes to mind,” he stated. We’re interested in tetanus and diphtheria as well.” His team is hoping to look at data on more people with HIV, including men, who were not included in the current study.

Augenbraun said that if further research confirms a correlation between the level of HIV-related immune-system malfunction and the lack of response to vaccines, it would bolster the argument for people to receive ART as early as possible so as to reduce the likelihood of having so-called HIV-associated immune amnesia.