Today’s powerful antiretroviral therapy (ART) helps fight back HIV infection and restore normal immune function. However, clinical evidence suggests that people with HIV who are virologically suppressed still have higher rates of comorbid viral infections than the general population.
Now, a new study in the Journal of Infectious Diseases suggests that ART does not restore the immune system completely back to normal. Instead, people with HIV may experience “immune amnesia,” in which the immune system slowly loses its capacity to recognize and fight off viral infections introduced during childhood or through a vaccine.
“Even with therapy, there’s something not quite fixed about the immune system,” said lead author Michael Augenbraun, M.D., FACP, FIDSA, who is vice chair of the Department of Medicine and director of the Division of Infectious Diseases at SUNY Downstate Health Sciences University and Kings County Hospital Center.
In the study, Augenbraun and his colleagues compared immune response among a group of 50 HIV-negative women and a group of 50 HIV-positive women on ART with low viral load. Each of these women had been vaccinated against smallpox during childhood, so they should all theoretically have similar levels of lingering protection against the smallpox virus.
Instead, researchers found that vaccine-specific antibodies declined rapidly among HIV-positive women but were maintained “indefinitely” among those without HIV. Meanwhile, a basic test of immune response (as measured by CD4+ T-cell responses after anti-CD3 stimulation) revealed no difference between the groups (P = .19), although HIV-positive women had significantly higher CD8+ T-cell responses (P = .039).
These results hint that—on the surface, at least—ART appears to restore immune function. Yet somehow the virus continues to weaken the immune system in subtle ways, even among people with an undetectable viral load.
Augenbraun stopped short of saying that the results in smallpox are generalizable to other viral infections, such as measles or herpes. He also emphasized that the results should not indicate anything negative about the success of ART.
The results “shouldn’t alarm people,” he said. Rather, they suggest “there may not be complete reconstitution of immune health in individuals. For the individual in the community who has HIV infection, there is no doubt in my mind: Take your medication.”
However, the results do indicate that the immune system’s “memory” is worse in HIV-positive patients, which could help explain why people with HIV have a fourfold higher rate of chickenpox (which manifests as shingles later in life), as well as other viral infections.
If the HIV virus is contributing to a loss of protective immunity, that means people living with HIV would be more likely to fall ill with childhood infections to which they were previously exposed or vaccinated against—infections like measles, mumps, chickenpox, or pertussis (whooping cough).
The results could also help unpack the role of chronic inflammation, which appears to contribute to “accelerated aging” among people living with HIV. Chronic inflammation leads to a whole range of health problems experienced by HIV-positive people, including cardiovascular disease.
The immune system’s ability to respond to viruses dwindles over time in everyone—but this effect appears to be accelerated in HIV. Augenbraun said there is a lot more research that is needed to determine if people with HIV would benefit from interventions such as re-vaccination.
“Like all studies, it’s a first step,” Augenbraun said. He noted that he and colleagues are planning a follow-up study among HIV-positive men, because this recent study was only conducted in women. For the time being, he says he’ll continue to study smallpox—an ideal model to study immune aging because the virus was eradicated from the United States back in the 1970s, meaning that patients who were vaccinated as children have not been re-exposed later in life.
Eventually, he said, researchers will need to confirm that these results can be replicated with other viral infections, like herpes, shingles, and measles.
“Like a lot of studies, it begs more questions than gives us answers,” he said. “If we can shed light on reducing risk of those things like cardiovascular risk and cancers, that would be helpful—but that’s down the line.”