Long Lasting HIV Drugs Hold Lessons For Us All

The successful results from a clinical trial of a new, long-acting HIV prevention drug are not just a critical milestone for those working on HIV/AIDS, but also for researchers working on other deadly infectious diseases. The results prove that in the absence of a vaccine for a viral disease like HIV, we can develop the next best thing—long lasting drugs that are highly effective at preventing infection when taken prophylactically.

The HIV drug, developed by ViiV Healthcare, is called cabotegravir and belongs to a class of drugs called integrase inhibitors. Integrase is an enzyme critical to viral replication. Block the integrase and you prevent the virus from replicating. It’s an approach that I and my Harvard research group identified nearly thirty years ago, now being applied to great effect. Results from a Phase III trial found that cabotegravir, when taken prophylactically, was 89% more effective in preventing HIV infection among women than Truvada, the current gold standard in HIV pre-exposure prophylaxis.

Its long-lasting effectiveness in women is important because women bear such a disproportionate burden of this disease. In some parts of sub-Saharan Africa, 80% of new HIV infections among adolescents are young women. Truvada and other HIV prevention medications that need to be taken daily have been highly ineffective in reducing the burden of disease in this key population for a number of reasons, not the least of which is the lack of autonomy and independence given to many young girls when it comes to their sexual health and ability to access HIV services. This new drug, which can be taken once and provides protection for up two to three months, could free women from daily dosing and significantly reduce the number of new HIV infections globally.

Another HIV drug, currently in development, has a similarly long-lasting effect, though it attacks a different part of the virus. GS-6027, developed by Gilead, attacks capsid proteins which protect the virus but also play an important role in viral replication, facilitating virus entry and exit when infecting new cells. In July, Gilead demonstrated that their anti-capsid drug could potentially protect people for up to eight months with one single injection.

Though GS-6027 and cabotegravir are very different drugs, they do have one important thing in common in addition to their long-lasting effect: they have an enormous therapeutic index. A therapeutic index is essentially the ratio between how much a drug harms the patient and how much it harms the virus, tumor, or other agent that is causing the illness. Ideally, you want drugs that do a great deal of damage to the agent but leave the rest of the patient free from harm. These two drugs do just that, as they target functions that are specific to the virus and have no corresponding function in human biology.

The success of these long-acting HIV drugs points to a strategy that may prove effective against Covid-19, influenza, and other infectious viral diseases. The early announcement by Pfizer of the potential effectiveness of their vaccine is promising, but there are still many unanswered questions. The Pfizer vaccine, like all the other Covid vaccines currently in development, does not prevent infection. It may prevent serious cases of Covid-19, but without any published data its still unclear how much a vaccine may limit the severity of disease.

What we do know is that a vaccine that does not prevent infection is unlikely to reduce the size of the pandemic, on its own. This means we can’t shift our focus away from other approaches that we know work—like mask-wearing and social distancing—and that we think could have a very high potential of working, like drugs that target the integrase and capsid proteins which have shown such great success against HIV.

It has been more than thirty-five years since we discovered the virus that causes AIDS and we still don’t have a vaccine. But now, for the first time, we may have not one, but two drugs—cabotegravir and GS-6027— that can effectively end the pandemic. If we pay attention to the lessons we have learned from that journey, I have hope that we will find a medical solution to Covid-19 far, far sooner.

© William A. Haseltine, PhD. All Rights Reserved.