HIV and AIDS were discovered decades ago but progress in combating the disease has been very slow. Research has focused primarily on managing the disease through combinations of antiretroviral drugs known as the AIDS cocktail. Recently, there have been promising developments in the areas of vaccine, prevention, testing, and cure.
The most effective vaccine to date was RV 144, also know as the Thai trial. It combined 2 failed vaccines and achieved a 30% protection rate, which is not considered an effective rate for widespread use. Colonel Nelson Michael, director of the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research and lead researcher of the trial, expects large-scale effectiveness studies to start in 2016. His goal is to have a vaccine with 50% effectiveness licensed by 2019.
Vaccines frequently start with animal testing, which has seen major advances. Rhesus monkeys are typically used in testing but simian immunodeficiency virus (SIV) is not an exact match for HIV.
A 2011 study at Caltech, funded in part by the Bill and Melinda Gates Foundation, created “humanized” mice that more accurately represent the disease in humans. The mice were given a human immune system by transplanting stem cells from bone marrow, along with liver and thymus tissue. The researchers then used a procedure called Vectored ImmunoProphylaxis (VIP) to directly injected antibodies via a harmless virus.
“VIP has a similar effect to a vaccine, but without ever calling on the immune system to do any of the work,” says Alejandro Balazs, lead author of the study. “Normally, you put an antigen or killed bacteria or something into the body, and the immune system figures out how to make an antibody against it. We’ve taken that whole part out of the equation.”
The mice were from exposed to HIV in increasing dosages from 1 nanogram, which is normally enough to infect a mouse, to 125 nanograms but they showed no signs of the virus when tested.
“We expected that at some dose, the antibodies would fail to protect the mice, but it never did-even when we gave mice 100 times more HIV than would be needed to infect 7 out of 8 mice,” explained Balazs. “All of the exposures in this work were significantly larger than a human being would be likely to encounter. If humans are like mice, then we have devised a way to protect against the transmission of HIV from person to person. But that is a huge if, and so the next step is to try to find out whether humans behave like mice.”
U.S. Food and Drug Administration (FDA) has approved Truvada, a drug that mimics and replaces an enzyme necessary for the virus to replicate. When compared with a placebo, it reduced the risk of HIV infection by 42% in gay and bisexual men who had unprotected sex with multiple partners and 75% in heterosexual couples where one partner was infected. The pill needs to be taken daily and costs up to $14,000 per year so it’s being marketed to high risk groups such as sex workers, IV drug users, and those with multiple partners or an infected partner.
“This is a pretty radical step, but I think it’s a necessary step,” said Dr. Lisa Sterman, who prescribes the drug. “We’ve come as far as we can with condom use and safe sex strategies. It’s the first time we have talked about a medication for prevention of HIV.”
Since the pill isn’t 100% effective, Truvada still encourages the use of condoms through free vouchers.
Early detection is crucial not only for treatment but also to prevent spreading the virus. A 2005 CDC study found that 54-70% of new infections in the U.S. are caused by people who don’t know they’re infected. Some individuals may be reluctant to go to a clinic out of embarrassment but now you can get tested in privacy of your own home.
The U.S. Food and Drug Administration recently approved the first over-the-counter HIV test, called Oraquick. The $40 kit includes a mouth swab that detects the presence of HIV antibodies in just 20 minutes. It’s 99.98% accurate in detecting the virus; however, negative results are only 92% accurate because the virus may not have reached a detectable concentration. It’s suggested that those who think they’ve been exposed get retested in three months to confirm a negative result.
TIME magazine named Oraquick one of the “Best Inventions of 2012.”
“The OraQuick In-Home HIV Test is a breakthrough product in the fight against HIV and AIDS because it empowers more people to learn their HIV status in the comfort and privacy of their own homes,” said OraSure CEO Doug Michels. “OraSure is extremely proud to be recognized by Time for this innovation.”
Until recently, scientists haven’t focused on a cure because it seemed such a lofty goal. Five years ago, a scientist who proposed researching a cure “would be laughed out of the room,” says Paula Cannon, a molecular biologist at USC’s Keck School of Medicine. “Nobody would give you money.”
That all changed thanks to Timothy Brown, also known as the “Berlin Patient.” Brown was HIV-positive but all traces of the disease disappeared after he received a bone-marrow transplant as part of a separate treatment for cancer. The donor had a genetic mutation that disables the receptor known as CCR5, which HIV needs to gain entry into immune cells. He no longer takes antiretroviral drugs and is still HIV negative 5 years later.
“There’s nothing like success to galvanize the research,” Cannon said. “People are daring to hope again that with a lot of hard work and ingenuity, scientists can deliver.”
At this year’s International AIDS Conference in Washington, D.C., Dr. Daniel Kuritzkes of Brigham and Women’s Hospital in Boston, announced two more cases of men being cured by bone marrow transplants but this time the donors did not have the mutation. Researchers say the patients underwent milder chemotherapy. It allowed the patients to continue taking their anti-HIV drugs. That protected the donor cells, which in turn killed off the patient’s infected cells in a phenomenon known as graft-versus-host disease.
“We’re never really going to be able to do bone marrow transplants in the millions of patients who are infected,” warns Kuritzkes. “But if you can stimulate the virus and eliminate those cells, we can protect the remaining cells from being infected.”
New drugs called histone deacetylase inhibitors can do just that. They block the enzyme that allows HIV to hide from the immune system and drugs. The problem is completely purging all reservoirs of latent virus so that there’s no resurgence.
In lieu of a true cure, some researchers are trying to stop the disease from advancing and thereby prevent the negative effects. Cannon hopes to have this so-called “functional cure” ready for clinical trials by 2014.
“We’re trying to do the poor man’s version of what happened to Timothy Ray Brown,” she told Quest. “We’re going to use the tools of genetic engineering to snip out the CCR5 gene in a patient’s own cells, and in that way make some part of their immune system be resistant to HIV.”