amfAR, The Foundation for AIDS Research

Curing HIV: Lessons from and for Children

Jeffrey Laurence, M.D., and Rowena Johnston, Ph.D.

Adults with HIV have a small number of infected cells in which HIV remains dormant, invulnerable to attack by the immune system or highly active antiretroviral therapy (HAART). It is generally believed that these latently infected cells persist lifelong—for at least seven decades—forming a critical barrier to curing AIDS. The three main strategies currently under investigation to cure HIV—pharmacological, immunological, and gene therapy—have all received amfAR support, and several have made it into human testing. However, the vast majority of these studies involved adults. A think tank organized by amfAR in San Francisco June 22–24 brought together 12 scientists involved in various aspects of HIV cure research, along with two bioethicists, to explore the potential for an HIV cure in infants and children. Some surprising, potentially game-changing, results were reported.

It is possible that the reservoirs of latent virus decay—self-destruct—much more quickly than has been observed in HIV-infected adults.Around the time HAART became available in the mid-1990s, doctors and researchers wondered whether these potent drugs that can shut down the ability of the virus to reproduce might ultimately cure patients of their infection. Hopes were soon dashed as scientists identified the small number of infected cells that came to be known as the latent reservoir of virus that would take about 70 years to eradicate with HAART. It has since become a truism that HIV cannot be cured by HAART. But an intriguing finding was reported at the think tank by Dr. Deborah Persaud of Johns Hopkins University relating to a cohort of children who had received ART within days to weeks of being identified as HIV infected by way of mother-to-child transmission. Several have continued on ART for as many as 15 years. It is not uncommon for some children identified soon after birth and put on antiretroviral therapy to test HIV antibody negative on standard HIV testing. 

Is it possible that when HAART is started in infancy, rather than adulthood, the length of time needed to eradicate HIV might be reduced? Dr. Mike McCune of UCSF presented data suggesting that a fetal, and perhaps neonatal, human immune system might respond very differently to HIV infection compared to that of an adult. These differences could provide a unique protective barrier that serves to reduce the chances of mother-to-child transmission of HIV. Based on this new information and data presented by others, it is possible that the reservoirs of latent virus decay—self-destruct—much more quickly than has been observed in HIV-infected adults.

Tackling the problem of curing HIV from a different angle, meeting participants discussed the possibility that an uninfected newborn’s stem cells might be used in an approach to an AIDS cure in both adults and children. These “cord blood stem cells,” obtained by draining blood from placentas removed following birth, are much more forgiving in terms of the need to match the donor tissue type to that of the recipient. Banks of such donated stem cells have been formed and tested for the CCR5 mutation that renders the cells HIV-resistant. Already one HIV-positive man in Utrecht, Holland, who required a transplant in an attempt to cure his leukemia-like disease, received such cord blood cells in mid-May. Once his anti-HIV drugs have been stopped, we will know if he is indeed the second “proof of concept” that AIDS can be cured by such a procedure. (Click here for information on the Berlin patient, the first person to have been cured of HIV.) In his discussions of gene therapy approaches for curing HIV, Dr. Hans-Peter Kiem brought up the possibility of engineering stem cells that have only one copy of the CCR5 mutation. This has a couple of advantages–cord blood stem cells with only one copy of the mutation are far more numerous than those with both copies of the mutation (which is required for resistance to HIV). If the cells already have one copy, it may be easier to genetically engineer them to acquire the other copy of the mutation than when starting with cells that have neither of the copies.

Several new avenues of investigation were illuminated, and intriguing hints at the possibility of a new way to cure HIV were presented. The think tank helped to shed light on a relatively understudied area, namely the differences in the challenges we may face in trying to cure HIV in the pediatric setting. Children infected with HIV represent an important group to address as we move towards our goal of curing *everyone* who has HIV.

Dr. Laurence is amfAR’s senior scientific consultant and Dr. Johnston is amfAR’s vice president and director of research.