The potential to apply the findings from the child cure case is intriguing. Each year around the world more than 330,000 infants are born HIV-positive. Although a regimen of antiretroviral therapy during pregnancy, sometimes with the addition of a brief regimen in infants after birth, can prevent around 98 percent of mother-to-child transmission of HIV, efforts to scale up this intervention have so far failed to reach all HIV-positive pregnant women. Even with universal coverage, some infants would still be born with HIV. What remains to be determined—and clinical research studies are currently being planned—is whether an early course of antiretroviral treatment in infants for a circumscribed period of time can eliminate HIV infection after it has occurred.
Dr. Rowena Johnston (second from left) was a panelist at a cure symposium preceding the 2012 International AIDS Conference.
(Photo: IAS/Steve Shapiro – Commercialimage.net)
The French cases described above are clearly examples of a functional cure—the patients all still have HIV, and yet have stopped taking their medication and have not progressed to HIV disease and AIDS. It is possible that such a cure might be effected more broadly, but the major challenge would be to identify HIV-infected people sufficiently early during the course of infection for the therapy to make this difference. Even so, it appears that only 10–15 percent of people are functionally curable this way.
It is less clear what type of cure Timothy Brown or the child have experienced. In both patients, trace amounts of the genetic material of the virus are sporadically detected. One challenge is knowing whether or not those results are “real.” In each case, the levels of virus are at the “limit of detection” of the assays being used. In other words, the virus hovers in the region in which the assays cannot definitively say whether or not the results are a false positive. Even if there really are traces of the virus left in these patients, what are the ramifications? In both cases, the patients have been off antiretroviral therapy for significant periods of time. If either had been harboring virus that was capable of replicating, in all likelihood that virus would have rebounded by now and would be readily detectable. It therefore seems most likely that any virus they still have is either incapable of replicating (and it is estimated that 99 percent of all viruses in any infected person are replication-incompetent) either because it is defective or present only in fragments. If the only HIV present in either patient is not capable of replicating, and therefore cannot behave in the deleterious ways we care about, can we say they have a sterilizing cure?
... it is clear there is much work to be done to find a cure—or possibly different types of cure—that can be applied to the estimated 34 million people living with HIV today. Although most researchers might say no, one could argue that this may be as close to a sterilizing cure as we will ever come, and that such fragments may not be as concerning as they sound. Geneticists have characterized stretches of DNA found in all humans, regardless of HIV status, called human endogenous retroviruses (HERVs). These HERVs share many of the characteristics of HIV. They are remnants of evolutionarily ancient infections with retroviruses (a class of virus to which HIV also belongs) that became incorporated into our genomes and those of our primate and mammalian ancestors. In fact, we have more DNA from these HERVs than we have DNA encoding our own proteins, leading one researcher to declare that “there is more virus in us than us in us.” Although yet to be confirmed, it is possible that trace amounts of HIV remaining in patients who are otherwise cured of the infection will be as harmless as these HERVs.
As promising as the recent reports of a cure have been, it is clear there is much work to be done to find a cure—or possibly different types of cure—that can be applied to the estimated 34 million people living with HIV today. That work will continue, with funding from amfAR, the U.S. National Institutes of Health, and other funders around the world. We owe a lot to the selflessness of the patients who have undergone the testing required to get us where we are today. Timothy Brown is probably the single most poked, prodded, and studied patient in the history of the epidemic, and he deserves our gratitude for his bravery in coming forward and his willingness to be tested in ways that advance the HIV cure research agenda. We are also very grateful to the mother of the cured child, who has allowed researchers to conduct the intensive tests required to confirm the cure of her child, to the French patients for subjecting themselves to repeated testing, and to countless others who have participated in studies that have not yet brought us a universal cure, but are teaching us each day what it will take to cure HIV infection and bring an end to this pandemic.
Dr. Johnston is amfAR’s vice president and director of research.
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