Two recent studies show that a new generation of antibodies that specifically target human immunodeficiency virus (HIV)-1 can drastically reduce virus levels, providing long-term control of HIV. These results suggest that antibody therapy may be useful to treat patients with chronic HIV-1 infections. The studies were published online in the journal Nature on October 30, 2013.
In Connecticut, 10,585 people are living with HIV (2011 data; ~1.2 million in the U.S.) and approximately 400 new cases of HIV infection are diagnosed each year (~50,000 in the U.S.). According to the Joint United Nations Program on HIV/AIDS, 1.7 million people worldwide died from AIDS-related causes in the year 2011 alone.
Antibodies are generated in response to infection and help eliminate pathogens. Some HIV-infected individuals do not develop AIDS (the most advanced stage of HIV infection) or have a delayed disease course. Antibodies from these individuals can have powerful HIV neutralization activity. It is these broadly neutralizing antibodies that two separate groups of researchers used to treat chronically infected rhesus and macaque monkeys. Their results show a rapid clearance of virus from the monkeys’ bloodstream. This suppression of HIV was sustained for several weeks or months.
These results are a step towards a cure for HIV. But, keep in mind that these studies were performed in animal models of HIV. Clinical trials in humans need to be performed to see if the effects of these broadly neutralizing antibodies can be translated into humans. Additionally, it is not currently known if these antibodies can cross the blood–brain barrier and suppress viral replication in the central nervous system (CNS), so whether this new therapy would be able to suppress HIV replication in the brain and spinal cord is an open question. Another issue is the fact that HIV has a high rate of mutation. This means that slightly different HIV proteins can be expressed within each individual, as well as across populations. This makes it likely that some people will have viruses that are resistant to some of the new therapeutic antibodies.
Currently, there are a slew of anti-viral drugs that can interfere with critical processes of the HIV virus. The problem with these drugs is that they do not work on the cells that are actually infected at the time you start treating the patient with these anti-virals. Rather they work on next round of cells – they prevent the virus that is being produced from infecting the new round of cells, but leave the old cells that are already infected alone. If the anti-viral therapy is stopped, these old or latent HIV-infected cells can still produce virus and re-ignite the infection.
There are essentially three hurdles to jump to develop a cure for HIV. The first step is to shutdown the spread of the virus. These new antibodies can very effectively suppress the replication of HIV. Check. The second step is to kill the cells that are actively producing virus. These new antibodies seem to be able to kill infected cells. Check. However, these new antibodies may not be able to affect the third step, which is the killing of the latent population of infected cells. Despite these limitations, this potential new therapy could still greatly enhance HIV treatment and would be a huge step toward a cure for HIV.
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