Major investments in science have resulted in the worldwide availability of over 20 anti-HIV drugs. When used in combination, these drugs restore health, prolong life and reduce transmission of the virus. HIV-infected individuals who harbor drug-susceptible virus, who have access to antiretroviral drugs, who can tolerate the drug side effects, toxicities, and other complications, and who are able to adhere to therapy, can maintain control of HIV infection indefinitely.
Despite these successes, these therapies have limitations. They do not eradicate HIV, requiring people to remain on expensive and potentially toxic drugs for life. They do not fully restore health as patients still experience co-morbidities such as increased cardiovascular disease, bone disorders or cognitive impairment. They are expensive and difficult to deliver to all in need.
Although the cost of delivering anti-retroviral drugs to the more than 34 million people now living with HIV has decreased substantially, and the availability of these drugs in resource-poor settings has steadily increased, the costs associated with delivering anti-retroviral drugs is overwhelming many organizations and public health systems. Estimates put the cost of the funding response to the HIV/AIDS epidemic by 2015 to be $22-24 billion per year, and $19-35 billion per year by 2031, with anti-retroviral treatment accounting for up to 70% of the total cost of care in the most affected countries.
Also, an effective and scalable HIV cure is to essentially stop transmission of HIV to those who are uninfected and restore the immunological function and normal health to those who are infected.
Scientists have known for some time now that latent HIV reservoirs, where HIV hides and persists, are one of the main barriers to finding a cure. This is precisely why treatment does not eradicate HIV and why, when treatment is stopped, the virus rebounds.
Several recent observations make scientists enthusiastic about pursuing cure research. For the first time ever there is now a "proof of concept", as scientists like to call it, for an effective cure. The case of Timothy Brown, the so-called "Berlin Patient", who received a stem-cell bone marrow transplant in 2007, and is now considered to be cured of HIV, has proved that a cure is at least possible. (See "Is He or Isn't He Cured?" in this issue.) This stem cell transplant worked because the donor was among the one percent of Northern Europeans who lack CCR5, the "doorway" through which HIV enters cells. While it is unrealistic to pursue this risky and costly therapeutic approach for most people, it has nevertheless gotten scientists thinking about the use of gene therapy to modify a patient's own immune cells to make them resistant to HIV infection.
The molecular biology regarding how HIV DNA becomes integrated in the chromosomes of infected people is the focus of intense research. This work has already led to a number of possible interventions, some of which are being tested in the clinic. Recently, in a test in HIV+ patients, David Margolis and colleagues showed that a dose of a drug that inhibits an enzyme involved in HIV silencing leads to rapid production of mv RNA in the patient's latently infected cells. This could make such previously unreachable viral reservoirs susceptible to curative strategies. For example, in combination with treatments that enhance host immune defense, unmasking latent virus might allow clearance of infection.
Scientists have also been aware of a rare group of HIV infected people who appear to have been naturally "cured" their own infection. These "elite controllers" are HIV+ but have no readily apparent virus in their blood. Scientists are gaining better understanding of this group.
There exists a unique cohort of patients in France who became HIV infected, started therapy early, and were able to successfully stop therapy without viral rebound (the "Visconti Cohort"). This study confirms the benefits of treating mv at the very early stages of infection, and there is an immensely valuable store of knowledge to be gained from analyzing the immunological characteristics that made therapy redundant for these patients. Understanding this group of people who efficiently control virus replication and reservoirs may lead to novel therapeutics.
Currently, the following strategies are being investigated, and it is expected that all of these strategies will be more efficient in combination with each other, alongside the use of antiretroviral therapy to at least protect the immune system of patients to prepare them for a cure.
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