In HIV, there is no simple way to define cure, because HIV can hide in deep cells in the body for many years and some people naturally have no detectable HIV in blood without treatment despite HIV continuing to grow and multiply in the body.
For this reason, it is not possible yet to determine if a person has a “sterilising” cure, where HIV has been completely eliminated from the body.
So, an alternative of a “functional” cure has been coined, where there is no evidence of HIV multiplying in the body and no evidence of the virus over a period without the use of ART (antiretroviral therapy). In a patient with a “functional” cure, the virus may reside in the deep cells (referred to as HIV reservoirs) but is not detectable with available laboratory tests.
The “Berlin” patient is the only person in the world who has been functionally cured of HIV. This was achieved through a bone marrow transplant, a similar complicated and risky procedure as the “London” patient had about three years ago.
This transplant replaces all the existing stem cells (that will become future blood cells) with a genetic variant that prevents HIV from entering these cells and infecting them.
In scientific terms, HIV multiplies in CD4 cells by entering the cells through attaching to a co-receptor, which is usually the C-C chemokine receptor type 5 (CCR5).
Some rare individuals, roughly one in 10000, have a genetic mutation of the CCR5 gene.
Patients with the mutation, known as a delta 32 deletion (because 32 base-pairs are deleted from the CCR5 gene) are resistant to HIV infection because their CCR5 co-receptor is faulty. This mutation is harmless to people but lethal to HIV.
Both the “Berlin” and “London” patients required bone marrow transplants for blood cancers unrelated to HIV. The “Berlin” patient had leukaemia while the “London” patient had Hodgkins lymphoma.
These bone marrow transplants, which were required for their cancers, provided an opportunity to see if bone marrow from donors with the delta 32 genetic mutation in the CCR5 gene, could suppress the patients’ HIV infection.
In short, the new blood cells in the “Berlin” and “London” patients from their donor bone marrows, are not able to become infected with HIV because of the faulty CCR5 co-receptor. This is why HIV is no longer able to grow and multiply in their bodies.
Bone marrow transplantation is a complicated and potentially life-threatening surgical procedure and should only be done if there is a compelling medical reason other than HIV. Further, HIV-resistant bone marrow donors are rare. Hence, this procedure is not an option except in very unusual circumstances, and even then, has a high risk of failure.
Regardless, the “Berlin” and “London” patients are providing us with important clues on the potential role of CCR5 genes in cure strategies and have inspired new research and advocacy toward an HIV cure.
Globally, it is estimated that there were about 36.7million people living with HIV and 1.8million new HIV infections in 2017.
South Africa is the worst-affected country in the world; about one in every five HIV-positive individuals in the world lives here.
The world has made great strides in treating people living with HIV, with about 21.7million people on antiretroviral therapy in 2017. With sustained treatment with antiretroviral drugs, HIV-positive people can have a lifespan similar to that of HIV-negative people. Besides treatment, substantial programmes are under way in South Africa to reduce the number of new HIV infections.
Despite this, HIV continues to spread. South Africa is at the forefront of research on HIV prevention and vaccines and has an important research initiative to find a cure for Aids.
The Centre for the Aids Programme of Research in South Africa (Caprisa) in partnership with the South African Medical Research Council, the US National Institutes of Health and the national government Departments for Health as well as Science and Technology together with the UCT and the National Institute for Communicable Diseases in Joburg are undertaking research on HIV reservoirs and are using locally discovered potent broadly neutralising antibodies to neutralise HIV in the reservoir to render them non-infectious as a cure strategy.
Recent promising data from monkeys indicate the potential value of this approach. Studies in humans are expected to start next year.
At present, there is no cure for Aids. Treatment and prevention programmes need to continue with vigour. Research is our hope, as a long but essential road, to create better treatment and prevention strategies and eventually a cure for Aids.
Karim is the director of Centre for the Aids Programme of Research in South Africa (Caprisa) and Caprisa Professor of Global Health at Columbia University. He is also pro vice-chancellor for research at the University of KwaZulu-Natal.