By Rowena Johnston, Ph.D.
If you’ve been following the news lately, you may be starting to wonder why anybody ever thought curing HIV was so challenging. On March 3 we heard the news that a child appeared to have been cured. Hard on the heels of that report came the news that 14 individuals in France had been functionally cured. So what do these cases mean? How are they similar, and how do they differ? And importantly for HIV research, where do we go from here?
Much depends on how a cure is defined. Researchers are used to thinking of a cure in two different ways. One type, a sterilizing cure, requires that HIV be eradicated from the body of the infected person. The second, a functional cure, is less stringent in that it requires that the patient is able to stop taking antiretroviral therapy without suffering any adverse consequences of the HIV that remains in their body.
The Berlin Patient
A decade ago, almost nobody spoke of curing HIV infection as a realistic goal, yet we find ourselves in early 2013 with not one, nor even two, but three different types of HIV cure.A decade ago, almost nobody spoke of curing HIV infection as a realistic goal, yet we find ourselves in early 2013 with not one, nor even two, but three different types of HIV cure. The first cure—the “Berlin patient,” who we now know as Timothy Brown—has been widely reported. Mr. Brown was living in Germany when he was diagnosed with HIV infection in the mid-1990s. His infection was well-controlled by antiretroviral therapy until he was diagnosed with acute myeloid leukemia about 10 years later. To treat the cancer, he received a stem-cell transplant, but his doctors took an extra step, finding a donor with a genetic mutation known as CCR5 delta-32. Naturally present in around 1–2 percent of Caucasians, this mutation renders people highly resistant to HIV infection. By transplanting cells from a donor with the mutation, doctors knew there was a good chance of curing Mr. Brown’s leukemia and hoped they might also eradicate—or at the very least bring under control—his HIV infection.
amfAR CEO Kevin Robert Frost and Timothy Brown, the “Berlin Patient”
Photo: Kevin Tachman
Since his transplant five years ago, standard clinical tests have failed to detect any HIV in Mr. Brown’s body, he hasn’t taken any antiretroviral therapy, and he has certainly not manifested any signs or symptoms suggesting he is progressing to AIDS. Why do we think this means he is cured of HIV? In almost all cases, a person who stops taking antiretroviral therapy will experience a rebound in virus, a resurgence to levels that are both easily detected and that predict a progression to disease and ultimately death.
When this case was first reported at a conference in 2008, scientists were skeptical. To quell doubts, numerous more detailed tests have been performed, using the most powerful laboratory tools available today. The viral outgrowth assay, single copy assay, PCR for DNA and RNA, antibody and other immune tests, immunohistochemistry, and digital droplet PCR results collectively suggest that if there are any pieces of the virus left in his body, they are not capable of replicating. In other words, although many scientists are still not willing to go so far as to say HIV has been eradicated from Mr. Brown, it seems increasingly likely that any virus that may be left in his body will not rebound and cause health issues associated with HIV disease. This is as good a cure as exists for any disease.
The Mississippi Child
When Drs. Deborah Persaud and Katherine Luzuriaga identified a child late last year who appeared to have been cured of HIV, they knew the case would require intensive documentation. The child had been born in Mississippi to a mother who tested HIV-positive during labor. Because this was the first point of contact between the mother and medical care, the doctors knew she had not taken antiretroviral therapy during pregnancy, an intervention that vastly reduces the chances of mother-to-child transmission of the virus. With this in mind, the pediatrician in charge of the case, Dr. Hannah Gay, decided to administer a treatment dose, rather than the usual prevention dose, of antiretroviral therapy to the infant just 31 hours after birth, to increase the chances that HIV infection could be prevented. She figured that if the infection occurred despite this therapy, at least the infant would be starting on therapy soon after birth. Infants are normally started on a treatment dose of antiretroviral therapy at six weeks or more, so there would be few other infants who had started antiretroviral treatment so soon after birth.
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