Why isn’t there a cure yet?

Dr. Rowena Johnston, vice president and director of research at amfAR, has the answer:
There has been only one known case of cure of HIV, namely the “Berlin patient.” It would be hard to overstate how important this case has been in terms of spurring optimism that a cure for HIV can be found, in the scientific community as well as other stakeholders (i.e., infected people). Of course, the drawbacks are that the procedures done on him cannot be replicated on an expanded scale. In fact, many doctors around the world have tried, and there has not yet been one instance where this cure has been replicated.

There is a group of patients in France, known as the VISCONTI cohort, who started taking antiretroviral therapy within weeks of infection, then eventually stopped taking the drugs. These people have been able to maintain low but detectable levels of the virus. The mechanism whereby they can keep their virus in check is not understood. Certainly, nobody recommends that patients stop taking their drugs; in almost all cases, the virus returns to very high levels. If some way could be found to safely withdraw patients from their antiretrovirals, this would be a great step forward, even though patients would still be infected. It is unknown whether the VISCONTI patients can still transmit their virus to others.

The major objectives of amfAR’s research road map address the four remaining roadblocks to curing HIV. These are all related to reservoirs, pockets of virus that persist in the DNA of infected cells. Antiretroviral therapy targets and helps contain any new viruses that these infected cells produce, but the blueprint for making those viruses remains within the cells’  DNA. If treatment is stopped, there is nothing to prevent that DNA blueprint from making new copies of the virus, which are able to spread unchecked. Therefore, in order to cure HIV, we need to tackle these four challenges:

• Chart the precise locations of viral reservoirs. Locating all the places where HIV is hiding in the body is a bit like finding a needle in a haystack. A particular body part—such as the brain or the gut—can harbor a reservoir of HIV. Particular cell types, including immune cells that are found throughout the body and are not limited to one place, can also be reservoir sites. We will not be able to eradicate or neutralize this latent virus unless we know exactly where all of it is.

• Understand how HIV persists in the reservoirs. Although scientists know that HIV hides in various reservoirs throughout the body and in different types of cells, many questions remain about why it persists in particular places and how it behaves.

• Record how much virus is in the reservoirs. When testing potential cure strategies, it is important to be able to assess whether the amount of virus in the body is diminishing. This will require highly sensitive measurement tools—tests that are capable of recording even a single particle of virus.

• Eliminate the reservoirs — via pharmacotherapy, immunotherapy, or cell therapy.

This shouldn’t be a zero-sum game. Many areas of HIV research continue to be important, including improving treatment, finding a preventive vaccine, and curing the infection. The scientific community can learn a lot about how HIV persists, and some circumstances under which it can be reduced or removed, via transplants. Many think that transplantation will not ultimately be a realistic way to cure millions of people. It’s difficult to know that in advance; perhaps if transplants could cure a lot of people, someone would work out how to provide transplants, or some cure intervention based on what we learn from transplants, to all the people who need to be cured.

Dr. Rowena Johnston, vice president and director of research at amfAR, is responsible for overseeing the foundation’s pioneering research program, targeting work directed at improving HIV prevention and treatment interventions, supporting the career development of young HIV and AIDS researchers, and aggressively pursuing a cure for HIV. In 2010 she was instrumental in forming the amfAR Research Consortium on HIV Eradication (ARCHE).