Arnaud Pontin (Image: Pixabay)
For people living with HIV, antiretroviral treatment remains the foundation of care. When taken correctly, these medicines suppress HIV replication, maintain an undetectable viral load, and prevent sexual transmission of the virus. Yet they do not completely eliminate HIV from the body.
Some virus can remain dormant inside certain cells, forming what researchers call the viral reservoir. If treatment is stopped, these reservoirs may allow HIV to begin multiplying again. The possibility of targeting these hidden cells is one reason immunotherapy has become an important area of HIV research.
The idea draws partly on progress in cancer medicine. Research in one medical field increasingly produces results that can be useful in another, and cancer studies have led to particularly interesting developments for HIV, including the design of new drugs and immune-based strategies.
Immunotherapy has changed the treatment of some cancers by replacing or supplementing intensive treatments such as chemotherapy. In certain cancers of the lung, throat, or colon, these approaches can be better tolerated by the body.
A close neighbor provided a personal example of this change. About 10 years ago, after many years of smoking cigarettes, he developed throat and lung cancer. He sought medical advice after losing his voice and experiencing discomfort in his throat. Following several examinations, the cancer was diagnosed, and he immediately began a series of chemotherapy treatments that caused significant side effects.
After several treatments, he decided not to continue, preferring to end things with less suffering. His oncologist then told him about an experimental immunotherapy treatment. Its principle was to stimulate or mobilize his own immune system so that it could better recognize and fight cancer cells. The treatment carried risks, but it involved far fewer side effects, so he agreed to try it.
After a very short series of infusions, he began feeling better within a few weeks. His voice returned, and the discomfort in his throat improved. The effects of immunotherapy can continue even after treatment has ended because the immune system may go on recognizing and attacking cancer cells.
Two years later, a scan was performed to assess the affected areas. The doctor’s smile conveyed the result: there was no longer any sign of active cancer. The only visible traces were scar tissue, remnants of the battle between his immune system and the cancer.
Could a similar principle be used against HIV?
Cancer immunotherapy has produced specialized antibodies, treatments that stimulate T lymphocytes, and genetically modified immune cells capable of targeting certain cancer cells. Researchers are now examining whether some of these technologies can be adapted to HIV.
The objective would not merely be to stop the virus from reproducing. Researchers are also seeking ways to make cells containing HIV visible, enabling the immune system to eliminate them.
One strategy often described as “kick and kill” involves reactivating dormant HIV in certain cells so that the virus becomes recognizable. The immune system or a targeted treatment would then be used to destroy those cells. Although the expression sounds simple, carrying out the strategy is extremely complex. The viral reservoir is made up of relatively rare cells spread across different tissues, where the virus can remain in a form that is difficult to detect.
Broadly neutralizing antibodies, or bNAbs, are another major area of study. Some of these antibodies can recognize numerous HIV variants. They may neutralize the virus directly, and some may also help alert the immune system to infected cells so that those cells can be destroyed.
Researchers are studying combinations of antibodies and their use alongside other immune treatments. The longer-term aim would be durable HIV remission without permanent reliance on antiretroviral drugs. These approaches are not yet treatments available in clinical practice; they remain experimental and are being evaluated in trials for their effectiveness and safety.
Genetically modified T lymphocytes could provide another route. CAR-T treatments, developed mainly in oncology, modify T lymphocytes so that they recognize certain characteristics of cancer cells and attack them. Researchers are exploring a comparable approach for HIV by modifying T lymphocytes to identify virus-infected cells more effectively.
This strategy is of particular interest because, in theory, it could direct the immune system against the viral reservoir itself rather than simply preventing HIV from reproducing.
Therapeutic vaccines are also part of this research. Unlike preventive vaccines, which aim to stop an infection before it occurs, a therapeutic vaccine would be intended for someone who already lives with HIV. Its purpose would be to stimulate or redirect the immune response so that the body could control the virus more effectively.
No therapeutic HIV vaccine is currently approved as a treatment that can replace antiretroviral drugs. Nevertheless, therapeutic vaccination is among the strategies being studied in the search for a functional cure.
That search requires a distinction between complete eradication and durable remission. Scientists may not initially seek to remove every copy of HIV from the body. A first achievement could be durable remission, meaning that the virus remains under control without daily antiretroviral treatment.
Complete eradication remains the ultimate goal, but the persistence of viral reservoirs makes it much more difficult. A future approach could therefore combine antiretroviral drugs, broadly neutralizing antibodies, immune stimulation, genetic modification of T lymphocytes, and other treatments designed to target reservoirs.
It would be an exaggeration to suggest that cancer treatments can simply be transferred to HIV. HIV and cancer are very different diseases, and their biological mechanisms are not interchangeable. They do, however, share one fundamental element: the immune system must recognize a cell that needs to be destroyed.
Cancer research has produced highly sophisticated tools for manipulating that immune response, and some of this knowledge can now be applied to HIV research. The central challenge is to identify cells containing dormant HIV precisely enough to eliminate them without causing significant damage to healthy cells.
For now, immunotherapy does not replace antiretroviral treatment. Properly used, antiretroviral drugs remain the basis of HIV care and enable people living with HIV to have a long and healthy life. Research is nonetheless moving toward the next question: after learning to control HIV, how can scientists reduce or eliminate the reservoirs that allow the virus to persist?
Immunotherapy could have an important role in that effort. One of the major lessons from cancer research may eventually be applied to HIV: instead of fighting the virus only with drugs, it might be possible to give the immune system the tools to find infected cells itself and destroy them.
That day has not yet arrived. Unlike the early years of the epidemic, however, researchers now possess biological tools that make it possible to seriously consider the possibility.
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