Many people living with HIV who adhere to regular antiretroviral therapy (ART) have undetectable levels of HIV in their blood. However, while these individuals are much less likely to spread the virus or experience most of the symptoms and complications, they still have latent HIV in certain tissues of the body, a phenomenon known as "HIV reservoir." If people with HIV with ART suppression stop taking the medication, harmful levels of HIV will lead to a "rebound".
Sustained viral remission, also known as a functional cure, refers to treatment or vaccination that would result in prolonged undetectable levels of HIV without regular therapy.
Effective ART allows HIV to remain suppressed in blood and tissues without replication to high levels. However, this effective treatment does not result in a cure for the disease because HIV can prevent these drugs and the immune system's natural response, remaining latent in a small number of long-lived immune cells. This small amount of HIV that persists in people on ART is called the HIV reservoir.
While individuals on ART with reproduction of suppressed hiv are much less likely to spread the virus or suffer from most of the symptoms and complications arising from HIV infection, such as the level of HIV in their blood known as viral load, will revert to harmful levels if they stop ART on account of the viral reservoir. Many people who are on ART with undetectable viral loads can live fully, with healthy lives and no risk of transmitting the virus to others, but maintaining this status requires regular treatment and draconian discipline.
A cure for sustained viral remission would allow a person living with HIV to maintain undetectable viral load without regular treatment or complex therapeutic regimens, as is often necessary in people living with HIV for a long time, or even newly infected persons , who may contract resistant strains of the virus because they would have been propagated by, for example, a sexual relationship in which the condom escaped or burst and neither partner in the frenzy of the moment can not perceive. A person in sustained viral remission would be considered functionally cured of HIV infection; he or she would still have to be infected with a very low level of virus but would be able to live their life with minimal risk of spreading HIV and without the need to take the medication daily. While there are still many existing challenges, both research for treatment and cure are working towards this goal.
Optimization of anti-HIV therapy
Because ART is so effective in reducing blood levels of HIV, some researchers theorized that introducing medication as soon as possible after infection could prevent HIV from building viral reservoirs and this would generate a form of formidable healing and that of could fail to make the ART. Experts initially believed that this had been the case in a child in Mississippi born in 2010. The child was infected with HIV from the mother at birth but started with an aggressive ART of 30 hours later. She continued ART for the first 18 months of her life before stopping the medication. She did not come to any specialist clinic until five months after her last dose of ART, but notably, doctors found that she had no detectable viral load. It continued to remain in sustained viral remission for two years when, in 2014, researchers announced that the child had detectable levels of HIV. While this was an unfortunate development, this case study sparked fundamental research on questions and showed that quiescence periods (Translator's note: temporary stoppage of development or other activity of an organism due to unfavorable environmental conditions) of the HIV in the absence of therapy may be possible. A lot of work is being done to try to understand where the virus was "hiding" in this girl and what led to the eventual rebound of their viral load.
In addition to selecting the right time to enter ART, researchers are also optimize ART for long-term therapeutic action that will be able to suppress viral load for long periods of time.
Long-acting therapeutic ART could offer convenience, cost reduction and ease of use for the millions of people around the world who must take multiple medications daily, or several times a day, to maintain a low viral load. While these advances in treatment do not replace the need for a functional, early and long-acting ART cure, it could act as one of the critical components capable of achieving complete viral suppression and reducing the size of persistent viral reservoirs to improve the success of remission viral and complete viral eradication in healing strategies.
Long-acting anti-HIV medication is also being tested for preventive use.
Strengthening the immune system
Most approaches to achieving sustained viral remission involve changes in the immune system to induce long-term control of HIV. Researchers try to manipulate the immune system with antibodies and therapeutic vaccines targeting HIV and HIV-infected cells and with therapies that alter the behavior of immune cells to better deal with the infection.
To broadly neutralizing antibodies, or bNAbs, are potent proteins that block infection of a high percentage of global HIV strains from infecting human cells and precipitating the death of cells that have already been infected.
Although they may develop naturally in some people with HIV over time, they usually do so in amounts too small to provide significant benefit, or they develop too late to control the virus, since HIV is mutated over time they are always one step ahead in the "arms race" that seems to be taking place. Researchers are exploring ways to bring various types of bNAbs naturally occurring in adequate amounts that can control HIV and lead to viral remission.
Potent bNAbs, several of which have already been tested in clinical trials may someday induce sustained viral remission. Alternatively, a therapeutic vaccine that induces the immune system to produce bNAbs may lead one day to long-term control of the virus.
Researchers are also exploring how immune cells can be manipulated to control HIV in the long run.
Chronic viral infections such as HIV infection lead to T cells depletion in which immune cells called "T cells," which fail to properly perform their normal functions of identifying and killing virus-infected cells. The scientists have developed antibodies known as anti-PD1 or anti-PD-L1 that have been observed in fighting T-cell depletion vitro and in cancer clinical trials by blocking a receptor-binding ligand cell that interacts by lethargizing these cells to atrophy and dying. Researchers are now verifying that these drugs may be able to help control HIV levels in the blood. Learn more about a recent clinical study of anti-PD-L1 therapy for HIV (external link).
Using another strategy in 2015, the scientists primed (traduror's note: see here) TK cells (specialized immune cells to destroy organic cells "defective", "potentially dangerous" or inadequate to the proper functioning of the "body" A kind of Gestapo) of T cells with fragments of HIV proteins. Scientists have discovered that these properly driven cells have eliminated HIV-infected cells in Petri dishes and in mice genetically modified to have human immune systems Note: A Petri dish, or Petri dish, is a cylindrical, flat, glass or plastic container that the laboratory professionals use for the culture of microorganisms. The name was given to this laboratory instrument in honor of the German bacteriologist Julius Richard Petri (1852-1921) who invented it in 1877 when working as assistant of Robert Koch (Translator's note: In spite of the reservations that the wiki made to the text, I could not simply ignore the mention of such a man). The study suggests that a therapeutic vaccine can in the same way increase the response of T cells to HIV can be successful in achieving sustained viral remission.