By Françoise Barré-Sinoussi, Sharon Lewin, and Steven Deeks
To date only one individual, Timothy Brown, is known to have been cured of HIV infection.
The process that cured Mr. Brown, a dangerous and expensive stem cell transplant from a donor known to be immune to HIV, was related to his treatment for acute myeloid leukemia. It is not a practical route to cure others, but it did prove one critical point — curing HIV is possible.
Finding a safe, affordable and scalable cure for HIV is a formidable challenge. Scientists have known for decades that HIV infection persists even when viral replication is effectively controlled by antiretroviral therapy. The virus can hide inside cells forever during therapy and re-emerge rapidly, and at any time, once treatment is stopped.
Despite these challenges, the quest to develop a cure for HIV has made remarkable advances over the past four years. Researchers have not been able to eliminate the virus from anyone except Mr. Brown, but in a handful of cases very early treatment with antiretroviral therapy has enabled an individual’s immune system to control the virus, without any need for treatment. These rare “post-treatment controllers” stay off therapy for years without any evidence of the disease, raising the possibility that pathways to achieving lasting control of the infection in the absence of treatment—a remission using the cancer model—may be available for discovery.
Linking HIV to Cancer
The parallels between HIV and cancer are striking. We now know that controlling HIV in the absence of therapy will require the generation and maintenance of powerful CD8+ — or “killer” – T cells that can target vulnerable parts of the virus. The challenge is remarkably similar to that in oncology, where the goal of innovative therapies is to generate killer T cells that recognize and clear cancer cells.
Many of the key immune pathways now being therapeutically manipulated to cure cancer were first discovered in studies of chronic viral infections, particularly HIV. For example, inhibitory pathways known as immune checkpoint blockers — that control immune responses and ensure self-tolerance — can reverse the brakes on killer T cells, enabling them to clear cancer (and presumably HIV-infected cells). Many people with once fatal cancers are now in long-term remission as a consequence of these new approaches.
Efforts are now underway to determine if these cancer therapies can be used to build up the immune system of patients with HIV in such a way that they too can achieve a durable and perhaps life-long treatment-free state of remission.
Both disciplines also struggle with the need to quantify the burden of disease. Cancer cells and HIV-infected cells are exceedingly difficult to distinguish from normal cells. They often also reside in tissues that are difficult to access. Intense efforts are therefore being aimed at quantifying the size, and distribution, of the disease in both disciplines, with often-similar approaches being taken.
Timothy Brown was cured by the work of a highly resourceful team of oncologists. His case illustrates that we need to do more to bring HIV and cancer research together — incentivizing scientists to work across diseases and ensuring that research funding allows for these synergies.
Transformative advances in the cancer field may well provide inspiration for future directions of a strategy to guide those working towards an HIV cure.