Long-lasting HIV drugs hold lessons for all of us

Positive results from a clinical trial of a new long-acting HIV prevention drug are not only a milestone for those working on HIV / AIDS, but also for researchers working on other infectious diseases deadly. The results show 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 in preventing infections 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 a critical enzyme for viral replication. Block integrase and prevent the virus from replicating. It is an approach that my Harvard research group and I identified nearly 30 years ago, now applied to great effect. The results of a phase III study found that cabotegravir, when taken as a prophylactic, was 89% more effective in preventing HIV infection among women than Truvada, the current gold standard in pre-exposure prophylaxis. to HIV.

Its long-term effectiveness in women is important because women bear such a disproportionate burden of this disease. In parts of sub-Saharan Africa, 80% of new HIV infections among adolescents are young women. Truvada and other HIV prevention drugs that must be taken daily have been highly ineffective in reducing the disease burden in this key population for a number of reasons, not the least of which is the lack of autonomy and independence given to many 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 to two to three months, could free women from daily dosing and significantly reduce the number of new HIV infections globally.

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

Although GS-6027 and cabotegravir are very different drugs, they have one important thing in common besides their long-lasting effect: they have a huge therapeutic index. A therapeutic index is essentially the relationship between how much a drug harms the patient and how much it harms the virus, tumor, or other agent that causes the disease. Ideally, you want drugs that cause a lot of damage to the agent but leave the rest of the patient harmless. These two drugs do just that, as they target specific functions of the virus and have no corresponding function in human biology.

The success of these long-lasting HIV drugs indicates a strategy that could prove effective against Covid-19, influenza and other infectious viral diseases. Pfizer’s first announcement of their vaccine’s potential efficacy is promising, but there are still many unanswered questions. Pfizer vaccine, like all other Covid vaccines currently in development, does not prevent infection. It can prevent severe cases of Covid-19, but without published data it is still unclear how much a vaccine can limit the severity of the disease.

What we do know is that a vaccine that doesn’t prevent infection is unlikely to reduce the size of the pandemic on its own. This means that we cannot shift our attention away from other approaches that we know work – such as mask wearing and social distancing – and which we think may have very high potential for work, such as drugs that target integrase proteins. and the capsid 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 actually end the pandemic. If we pay attention to the lessons we learned from that trip, I hope we will find a medical solution to Covid-19 much, much sooner.