The often-overlooked Düsseldorf patient

The London patient mentioned in this issue of TreatmentUpdate is not the only patient who has entered into remission from HIV. Researchers in the German city of Düsseldorf have reported interim results on a patient who has had remission from HIV after a bone marrow transplant from a donor with the rare genetic delta-32 mutation. This mutation results in a person not having the CCR5 (R5) co-receptor on their cells, making them resistant to infection by most strains of HIV.

The case of the Düsseldorf patient

In October 2010, a 42-year-old man from Düsseldorf was diagnosed with HIV infection. His doctors prescribed the following regimen of anti-HIV drugs (ART) for him:

• darunavir + ritonavir + TDF + FTC

In January 2011 the man was diagnosed with acute myeloid leukemia, a cancer of the white blood cells produced in the bone marrow. Doctors then changed his ART to the following combination:

• raltegravir (Isentress) + TDF + FTC

Isentress belongs to a class of drugs called integrase inhibitors. In general, most integrase inhibitors tend to have few interactions with other medicines, particularly compared to darunavir and ritonavir, which belong to a class of drugs called protease inhibitors. Doctors had prescribed chemotherapy and did not want any interactions with his ART, as maintaining suppression of HIV would help his immune system in its struggle against cancer. His viral load was less than 40 copies/mL.

After five courses of chemo the man went into remission, but in 2012 he relapsed. Doctors then prescribed three courses of new combinations of chemo, but these failed to kill the cancer.

Doctors then decided to wipe out his current immune system and give him a stem cell transplant from which a new immune system could arise. They found a donor with the rare delta-32 mutation who had a similar genetic makeup to the patient.

Doctors then gave him a conditioning regimen to try to destroy the leukemia as well as his bone marrow so that the stem cell transplant could take hold.

Post transplant

The stem cell transplant was successful and the man’s cancer resolved. A new immune system was formed and though he always maintained good adherence to ART both before and after his stem cell transplant, his CD4+ cell count in 2014 was less than 260 cells/mm³ and his viral load continued to fall below the 40 copy/mL mark.

In mid 2014 doctors changed his ART to the following combination:

• dolutegravir + abacavir + 3TC (all three drugs are in one pill called Triumeq, taken once daily)

In 2015, his CD4+ count began to rise, reaching 400 cells/mm³ by the end of that year. By October 2018, his viral load continued to be suppressed and his CD4+ count had risen to 650 cells/mm³.

Looking for HIV

After his stem cell transplant and the subsequent creation of his new immune system, doctors at the university of Düsseldorf performed ultrasensitive tests on samples of his blood and lymph nodes and could not find any HIV. Given the limits of current technology to detect residual HIV, the only way to be sure that the virus has been eradicated would be to cease taking ART and monitor the patient for several years, while continuing to perform complex laboratory tests. So, in November 2018, the patient and his doctors decided to withhold ART.

The patient remains under intense medical surveillance and, at least initially, has had his blood drawn twice weekly so that it can be checked for any trace of HIV. Once a month, researchers conduct complex testing of his immune system, checking for HIV-infected cells and any signals that CD4+ and CD8+ cells have encountered HIV.

So far HIV has not been found and the man’s immune system is healthy. It is possible that after several additional years of monitoring and continued lack of any trace of HIV that doctors in Düsseldorf will declare this man cured. Right now, though, he is considered to be in remission. This alone is very promising.

Resources

The Canadian HIV Cure Enterprise (CanCURE)

—Sean R. Hosein

REFERENCES:

1. Jensen B-E, Knops E, Lübke N, et al. Analytic treatment interruption (ATI) after allogenic CCR5 delta-32 HSCT for AML in 2013. In: Program and abstracts of the Conference on Retroviruses and Opportunistic Infections, 4 – 7, March 2019, Seattle, Washington. Abstract 394.
2. Kobbe G, Kaiser R, Knops E, et al. Treatment of HIV and AML by allogeneic CCR5-d32 blood stem-cell transplantation. In: Program and abstracts of the Conference on Retroviruses and Opportunistic Infections, 22–25 February 2016, Boston, MA. Abstract 364.