In the 1980s, HIV was a death sentence. Today, three decades later, clinical research has produced therapeutic breakthroughs that have turned HIV into a chronic yet manageable disease. Drugs that approach the disease from different angles, in combination with each other, are able to reduce viral load—the amount of virus in the body—to levels that are undetectable.

These drugs not only protect an individual infected with the virus from getting AIDS, they significantly limit the ability of the disease to spread from one person to another.
HIV is big business for drug makers like Gilead and ViiV who dominate the marketplace with established brands like Truvada, Atripla and Stribild, and newcomers like Triumeq and Genvoya, each one either currently making or forecast to generate $3 billion or more in sales every year.

Even with all the scientific advances, clinical research has yet to find the Holy Grail: an HIV vaccine. It isn’t for lack of trying. There are 117 clinical and preclinical studies currently looking for the answer.

In the historical context, 30 years may not seem like a lot of time. It took over 100 years to find a vaccine for typhoid, 80 years for pertussis and 47 years for polio. But as science progresses, lag time between virus identification and vaccine discovery has been getting shorter. It only took 16 years to develop a vaccine for the hepatitis B virus, for example.

Since the discovery of the human immunodeficiency virus, a number of clinical trials have held promise, but ultimately failed to achieve their mission. In 2007, Merck’s highly anticipated STEP trial was terminated, marking a major setback not just for the sponsor but for vaccine development in general. The trial failed to protect against infection and failed to raise T-cell levels, negating the premise that stimulation of T-cells was the answer.

Should we be concerned that vaccine development for HIV, which has been ongoing since the 80s, has yet to yield a viable vaccine candidate?

Maybe not. The scientific challenge is an unusually difficult one, requiring researchers to develop a vaccine against a retrovirus the likes of which they’ve never seen before.

HIV is particularly adept at hiding itself from the body’s natural surveillance, allowing it to mutate and replicate quickly. Because the human immune system has a hard time detecting the presence of HIV, it can’t keep up with it. A successful vaccine would only have a small window of time—less than 24 hours—in which it could search and destroy HIV in order to be effective.

In 2009, investigators in what was known as the Thai Trial (named for its central site in Thailand) were able to trigger an immune response in people infective with HIV. Though the outcomes were not significant enough for the drug to be used as a vaccine, it was the first and only successful proof-of-concept that a vaccine could reduce transmission rates. Building on the Thai study, a new trial, known as the Uhambo Study, is now underway in South Africa using the same product, but with an effort made to make the vaccine remain active in the body for a longer period of time.

While it is possible that the trial will not yield a comprehensive vaccine, scientists believe any degree of protection could still be important in prevention when combined with antiretroviral drugs and other interventions, like medical male circumcision. The Uhambo Study will take 10 years to complete, with initial results expected for publication by 2019.

About six years ago, scientists discovered something interesting in the blood of a so-called “long-term nonprogressor”—a person who had HIV and whose body controlled the infection for more than 15 years without medicine. As it turns out, in roughly 15% of people infected with HIV, the immune system learns over time to make antibodies that fight a broad array of HIV strains.

This year a new clinical research effort is underway to explore the effectiveness of these broadly neutralizing antibodies. Whereas the Thai Trail focused on non-neutralizing antibodies, this new approach involves testing a manufactured version of a natural antibody delivered directly into the patient’s bloodstream via an intravenous infusion.

Considered a landmark clinical trial, the AMP Trial is one of two parallel studies that will span three continents and involve more than 4,000 participants—2,700 men and transgender people who have sex with men at 24 sites in the U.S., Brazil and Peru, and 1,500 sexually active women at 15 sites in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe.

The study promises a whole set of scientific breakthroughs that could advance the science needed to make a potent HIV vaccine, and open a second avenue to pursue in the quest for a vaccine.  

Matthew Howes is executive vice president, Strategy & Growth for PALIO, an inVentiv Health company. A leader in digital strategy, he has provided the fuel for digital businesses visited by over 100 million people every month. Email matthew.howes@inventivhealth.com.

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