Stephen Kintz
Apr 15, 2012

HIV: Why developing treatments and vaccines is so difficult

A nurse holds vials of blood during tests of an AIDS vaccine in Bangkok.Researchers from University of California, Los Angeles (UCLA) and a joint research venture by the US Army and the National Institute of Allergy and Infectious Diseases (NIAID) have recently published two papers on a possible new treatment and vaccine for HIV, respectively. According to the Centers for Disease Control, 1.2 million people are infected with HIV in the United States alone and about 34 million are infected worldwide. HIV has long since reached epidemic proportions. Yet, if anyone wants to understand the HIV epidemic, they need to understand the limitations and weakness of both approaches to combating HIV.

In research published in 2009, the UCLA team demonstrated an ability to turn human blood stem cells into mature HIV-fighting T cells. In a study published on April 12, the researchers took these T cells and implanted them in humanized mice infected with HIV. They found that after taking samples from the mice on week two and six, that the number of mature T cells had increased and the levels of HIV decreased. This suggests that the researchers have developed an effective means for fighting HIV. The researchers hope that this will eventually translate into better treatments and, possibly, a cure.

In a 2009 vaccine trial, known as RV144, researchers from the U.S. army and NIAID conducted a vaccine trial that involved over 16,000 people in Thailand. The researchers found that the vaccinated group was 31 percent less likely to contract HIV against a control group, who only received a placebo. Unfortunately, the trial was only moderately successful, so there has been a several year analysis on the data to try and understand why. Recently, the scientists published the results of this analysis in the New England Journal of Medicine. They found that the vaccine was most successful in people with high levels of an antibody, V1V2. The researchers plan to take this information to animal models to determine if the V1V2 antibody is helping the vaccine protect people against HIV.

The HIV virusBoth methods for combating HIV are fundamentally different, with one trying to kill the disease in infected individuals and the other trying to prevent infection. However, both methods suffer from the same weakness against the disease: HIV mutates at an extremely fast pace and our efforts to counteract the disease struggle to keep up. Both methods can only treat HIV infections that have not mutated beyond the human immune system's ability to recognize the infection. The UCLA researchers are hoping that they are capable of detecting the altered virus and producing enough altered T cells to destroy the infection. With a vaccine, the researchers will need to produce several vaccines for each strain of mutations or find some universal mechanisms that allow the immune system to respond to the disease. It is currently unclear if this is possible.

Unfortunately for the researchers at UCLA, HIV has another mechanism that allows it to survive treatment. HIV can survive in a latent form. Typically, once the HIV virus has injected its RNA into a cell (typically, a T cell), the cell explodes open with a copy of the virus. This, of course, kills the cell. Unfortunately, HIV can also become latent, which means that the RNA simply sits and replicates itself with the cell without killing the cell. In this latent form, the virus cannot be detect by the immune system or treatments designed around the immune system. So, even if the researchers think they have killed the entire disease, it is possible for the disease to be hidden with a cell that will eventually produce more of the HIV virus.

Therefore, HIV is an extremely hard disease to treat and kill. While the vaccine would probably be ideal, no one is sure if it is possible. Also, it is obvious that altering T cells might prove a useful treatment for HIV, but further treatments that target the latent form of the disease will need to be developed for the treatment to ever be an effective cure. In fact, it appears that prevention, vaccination and treatment will all play a small part in helping combat the disease.