Timothy Henrich and Daniel Kuritzkes from Brigham and Women’s Hospital and Harvard Medical School in Boston recently presented their latest results on two HIV patients who underwent a bone marrow transplant a few several years ago. After three months, no virus was detectable in their peripheral blood. Years later, it was decided to try to stop the antiretroviral treatment of these patients under high medical supervision. After 7 or 15 weeks, there is still no sign of the virus in their blood.
New Bristol - HIV virus model
Source: Flickr/creative commons licence/Biker Jun
The seventh International Aids Society (IAS) conference on HIV pathogenesis, treatment and prevention took place at the beginning of July in Kuala Lumpur. One of the major breakthroughs was presented by Timothy Henrich and Daniel Kuritzkes from Brigham and Women’s Hospital and Harvard Medical School in Boston. After years of living with HIV and combination antiretroviral therapy (cART), two Hodgkin lymphoma patients in remission stopped their HIV treatment under extreme medical surveillance. No sign of the virus was found in their blood after 7 or 15 weeks, depending on the patient.
HIV patients treated for Hodgkin lymphoma
Two long-term HIV-1 patients treated with cART for several years were diagnosed with Hodgkin lymphoma in 2006. After numerous therapies, such as chemotherapies, they both underwent a bone marrow transplant from an external donor. To avoid too many side effects, the immune system of the patients was suppressed before the operation, but their bone marrow was still capable of producing new blood cells.
In an article published in the Journal of Infectious Disease in June, Henrich et al. reported that the virus was still detected after the transplant. Nevertheless, no sign of it could be found in their peripheral blood cells up to 21 and 42 months later. In addition, they showed that the donor cells completely replaced the host ones and that the cART protected them from being infected.
HIV patients no longer under cART
At the IAS 2013, Henrich and Kuritzkes presented the continuation of this study. After 4 to 6 months of discussion with ethical and institutional boards, the patients, and their clinicians, it was decided to stop the HIV treatment. The patients were very well aware that this was a big risk, as they were doing well, both with HIV that was undetectable and their cancer in remission. In addition, among a number of different symptoms that could appear, not only could the virus come back stronger, but the risk of the cancer rebounding could not be excluded either.
At the IAS 2013 press conference, Tim Henrich explained that it was worthwhile to try, with very frequent monitoring and particular attention to these patients. Because of the mortality risks, it has been difficult, since the end of the 90’s, to obtain a transplant when you are HIV-positive. “[Because of these conditions], I feel like I need to give back to scientific knowledge after having the possibility to have a healthier life,” said one of the patients.
Emily Hanhauser, senior laboratory technician
in Henrich’s lab, working on the ‘Boston patients’
samples in the retrovirology laboratory
Towards a future HIV cure?
After 7 and 15 weeks depending on the patient, still no trace of the virus could be found in their blood. In quite all other cases of cART interruption, the virus has resurfaced quickly, in two to three weeks. Only Timothy Ray Brown, known as the 'Berlin patient' has been living HIV-free for six years. In 2007, he received a transplant of bone marrow containing cells resistant to HIV infection. Today, he is considered cured.
At this stage, for the two ‘Boston patients’, who didn’t receive HIV-resistant cells, numerous hypotheses can be made about a probable multifactorial explanation, but it will take years to know more about what is really happening. As the virus can be found latent in various reservoirs like the brain and the gut, unchecked in this case, a longer follow-up is required to be sure that the virus will not be back in a year or two.
Tim Henrich said that “This study was done with two goals. First, to show that nowadays, it is safe and potentially beneficial for patients with HIV who need a transplant to receive it. Second, to learn a lot more about how the immune system and the residual reservoirs of viruses interact. We are hoping that we can learn some basic physiology and basic pathogenesis of how HIV persists and how we can use components of transplant without doing full transplantation.” They are working with a long-term view and hope to acquire enough information to develop new strategies.
With these new results, researchers are one step closer to a real solution.
To find out more:
Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation. Henrich TJ et al., J Infect Dis. 2013 Jun 1;207(11):1694-702.