The world’s biggest conference on the fight against the scourge of HIV/Aids just ended in Durban, South Africa. Thousands of delegates including scientists, HIV/AIDS activists, advocates and journalists were excited at the possibility of getting an HIV cure according to the latest research.
This was during a pre-conference symposium dubbed ‘Towards an HIV cure research’ in the week-long 2016 International Aids Conference which took place from 18th – 22nd July 2016.
Dr. Anthony Fauci, the Director of the US Institute of Allergy and Infectious Diseases (NIAID) said that the search for an HIV cure is indeed challenging but not impossible. He explained that in HIV cure research, the term ‘cure’ refers to a strategy that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease.
Two types of cures are being discussed today. A “sterilizing” cure that would completely eliminate the virus and a “functional” cure that would suppress HIV viral load, keeping it below the level of detection without the use of antiretroviral therapy (ART).
Dr. Fauci added that at this level, the virus would not be eliminated from the body but it would be effectively controlled and prevented from transmitting. He said that some scientists are now using the term ‘remission’ borrowed from the cancer field because it is difficult to distinguish these types of cures.
Explaining the term remission, he said that it is generally defined as the lack of readily detectable rebound of the virus for some period of time after stopping drugs. However, he quickly added that this period is not yet defined by the scientific community.
It is however important to know that researchers are still debating and discovering what it means to be biologically cured of HIV. Although some possible cases of functional cures have been reported, it takes time to be certain that HIV can no longer cause disease, because it is known that at even low levels the virus below the limit of detection can increase the risk of certain illnesses and ultimately lead to AIDS.
Many cure strategies being investigated
Prof. Sharon Lewin Director of The Doherty Institute at the University of Melbourne, Australia said that there are four broad strategies being explored. Each of these strategies takes a different approach to the fundamental challenge of HIV infection that the virus can hide out in cells that are not active and dividing. As long as the cells are not dividing, the virus isn’t copying itself and is considered to be ‘latent’.
Cells that carry latent virus are, collectively referred to as viral reservoirs. Most of the viral reservoir is in memory CD4+ T cells, which are designed to live in the body indefinitely. A truly effective cure will either have to eliminate these viral reservoirs or ensure that the virus that gets activated from resting cells does not re-establish infection in the body.
SO WHAT ARE THE STRATEGIES?
‘Shock and kill’
This two-step strategy aims to flush (or shock) the virus out of its resting cells and then follow it up with effective killing of the infected cells. Many of the shock agents being considered are currently used as cancer treatments. The ‘kill’ component of this one-two punch could involve a therapeutic vaccine, if an effective one can be developed or other interventions to improve the immune response.
Gene editing (manipulation)
This strategy seeks to change a person’s cells so that HIV can’t infect them. This can be done by altering the genes of a person’s immune cells. Genes are the blueprint for the cell’s architecture. An alteration of that removes a key receptor or protein that HIV uses for infection can make the cell resistant to infection.
Gene editing or gene therapy is targeting many of the same targets used in treatment. Since HIV needs to be inside cells to copy itself, such a strategy might effectively stop HIV from spreading in the body.
The most advanced gene therapy is technologically complex; it involves extracting CD4 T cells from HIV+ individuals and then modifying them with a method that disables the gene that encodes the CCR5 receptor (which most HIV variants use as a foothold to gain entry into cells)
Stem cell transplants
Another strategy is stem cell transplant, Hematopoietic stem cells produced in the bone marrow, are the source of all blood cells in the body. Stem cell transplants are used to treat life threatening illnesses such as cancer. They carry a high risk of side effects. Only one person, Timothy Brown, who was apparently cured of HIV, received a stem cell transplant for cancer treatment.
His transplant contained cells that could not be infected by HIV because they lacked a key receptor (CCR5) on their surface. Stem cell transplants are preceded by a process called conditioning. Conditioning eliminates an individual’s immune system to make room for the donor system and decreases the likelihood of transplant rejection. In HIV + individuals, conditioning eliminates HIV infected cells. Stem cell transplants are a last resort for people with both cancer and HIV. This strategy is not scalable.
Therapeutic vaccines
Therapeutic vaccines are designed to boost or induce immune responses against HIV in someone who is already infected with the virus. Most of these vaccines are aimed at increasing the potency of the natural killers of HIV (e.g, HIV specific CD8+ T cells and NK cells). The hope is that vaccine-induced immune responses can contribute to control of the virus in the absence of antiretroviral treatment, and perhaps also help eliminate latently infected cells.
What are the challenges related to HIV cure research?
Prof. Lewin explains that there are many issues that make cure research difficult. First, there is no clear measure of HIV reservoir. The two leading approaches are to measure the number of HIV RNA copies in the blood, or the number of HIV DNA copies in cells.
Just measuring HIV RNA doesn’t necessarily give an accurate picture, either, since the cheapest and most available technologies cannot distinguish replication-competent virus. A more precise assay, the quantitative viral outgrowth assay, requires the use of large numbers of cells and cannot be done with a simple blood draw.
A second major challenge is that cure strategies currently under investigation carry unknown risks and benefits. Figuring out how to communicate these unknowns to potential trial participants will be an important part of any cure clinical trial.
All these strategies being developed require expensive equipment and specific training to administer. To show success or failure, additional resources will be needed and yet the resources are not available in most global settings.
Social workers come in
And that is exactly when the social workers come in. In order to test whether a person has been cured, they need to stop effective antiretroviral treatment so that viral rebound, if any, can be measured. There are however no standardised guidelines for how to time such ‘treatment interruptions’ so that they minimize risks for cure trial participants and their partners.
That is why, social workers are also calling upon our advocates to sensitize communities about this important stage of the search for an HIV cure and also urge research institutions, policy makers and funders to remain focused on the need for an HIV cure.
“HIV Cure research has the potential to alter the future of this epidemic”, said Nobel Laureate Francoise Barre-Sinoussi, co-chair of the International Aids Society Towards an HIV Cure Initiative.
With 37 million people currently living with HIV worldwide, and another two million newly infected each year, an effective approach to curing or achieving sustained remission of HIV infection would be a ground breaking advance in global health.
Research to achieve such cures is in a formative stage, but significant advances are being made and are explored in Durban during AIDS 2016 that has brought together over 18,000 delegates from across the globe.
