How a young child fought off the AIDS virus

 

In 1996, a baby infected with HIV at birth was started on anti-AIDS drugs. But at age 6, against the advice of doctors, her family stopped treatment. Twelve years later, the young French woman is still healthy, with no detectable virus in her blood. Her unusual case, reported today at an international AIDS conference in Vancouver, Canada, may hold clues that might help other HIV-infected people control their infections without antiretroviral (ARV) drugs and offer insights to AIDS vaccine developers.

The case adds a new wrinkle to earlier reports of people who manage to control their HIV infections on their own: the so-called elite controllers, who never receive treatment yet suppress the virus to low levels, and posttreatment controllers like the “Mississippi baby,” who stopped taking ARVs at 18 months of age and remained virus free for more than 2 years. In 2013, many researchers thought that child might have been “cured,” but HIV came back strong after 27 months off treatment.

This time, it’s clear that the French woman is not cured: Investigators have found strong signals of HIV DNA in her immune cells and can readily induce them to produce virus, says Asier Sáez-Cirión, a viral immunologist at the Pasteur Institute in Paris who reported on her case. But she is the first documented HIV-infected child to go off treatment and remain in remission for this length of time. “We don’t know why this happened,” Sáez-Cirión says.

Some clues may come from a group of people infected by HIV as adults, known as the VISCONTI cohort, who went off ARVs and did not have the virus return for many years. As Sáez-Cirión and colleagues described in the March 2013 issue of PLOS Pathogens, the adults were diagnosed shortly after they became infected, began ARVs immediately, and stayed on them for an average of 3 years. At the time of that publication, the average person had been off ARVs for 7 years. Sáez-Cirión and co-workers have added the new case to the VISCONTI group, which now has 20 members.

The people in the VISCONTI cohort look strikingly different from elite controllers, the 1% of HIV-infected people who never have high virus levels, even in the first weeks of infection, despite never receiving treatment. Although no single factor explains the unusual ability of elite controllers to rein in HIV, many are genetically predisposed to have high levels of the CD8 lymphocytes that identify and eliminate cells infected with HIV. 
Posttreatment controllers, like the people in VISCONTI, have high virus levels shortly after infection and their immune systems rapidly deteriorate. Paradoxically, many have a genetic background that predisposes them to a weak adaptive immune response to the virus.

Sáez-Cirión thinks they may be receiving help instead from the more primitive and less powerful “innate” immune system that serves as a frontline defense against invaders. The researchers suspect that the innate immune system may be strong enough to contain HIV if people have very small reservoirs of viral DNA. Members of the VISCONTI cohort began treatment so quickly after infection that those reservoirs never got a chance to fill.

Another, somewhat counterintuitive, possibility is that the weak immune response in posttreatment controllers helps limit the size of the reservoir before the drugs are even started. HIV preferentially targets and infects the CD4 white blood cells that help fight infections. A weak CD4 response to the virus means fewer targets for it to infect.

Sáez-Cirión also suggests a third possibility: that some posttreatment controllers happen to be infected with a weaker form of the virus—a mutant resulting from HIV’s error-prone replication.

Anthony Fauci, who heads the U.S. National Institute of Allergy and Infectious Diseases, says he’s intrigued by the new French case and how it fits together with the Mississippi child. “There’s something about the immune system of a very young person,” Fauci says. “The Mississippi child was a tickler for us, and I wouldn’t throw it out the window—27 months is a long time. Maybe, somehow, the way that child kept the virus under control is the same as the new case. I have an entirely open mind.”