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Substantial global efforts have been made to address the HIV epidemic yet challenges remain.

Why a cure for HIV remains elusive

By Paula Cevaal, Michael Roche and Sharon Lewin, The Peter Doherty Institute for Infection and Immunity in Melbourne

 

Advances in cancer treatment, gene editing and mRNA technology are helping researchers in their pursuit of an HIV cure.

World AIDS Day on December 1 is an opportunity to reflect on the spectacular progress made towards preventing and treating HIV — but a cure for the virus 39 million people are currently living with remains elusive.

While antiretroviral therapy (ART) for HIV stops the virus from replicating, stops people from getting sick and stops a person with HIV from infecting others, treatment for people with HIV must be continued for life.

ART doesn’t cure HIV because the virus has a sneaky trick: it can hide and become inactive, a state known as latent infection.

Once a person stops treatment, the latent virus becomes active again and resumes replication.

But drawing on advances in cancer treatment, gene editing and mRNA technology, researchers continue to make significant strides in pursuit of an HIV cure.

Globally, scientists are actively developing and testing interventions that specifically tackle latent virus, with the eventual goal to achieve virus-free control after stopping antiviral treatment.

HIV cure: from the theoretical to the possible

In the 40 years since the discovery of the virus, complete eradication and cure of HIV have been achieved in six exceptional cases.

These individuals all underwent stem cell transplants to treat life-threatening blood cancers, with all but one receiving stem cells from donors with a rare genetic trait that makes their cells resistant to HIV.

As a result, all six individuals were able to stop ART after the intervention, and the virus has not reappeared after years of follow-up.

However, due to the high risk of complications associated with stem cell transplant procedures, they are not a viable pathway towards a cure for the broader HIV community. Nonetheless, these cases have shown the world that an HIV cure is possible.

Approaches to safely stopping ART: reduce and control

Several therapeutic strategies are under investigation to reduce and control the latent HIV reservoir, without the need for invasive stem cell transplants.

One approach seeks to find treatments that force the latent virus out of its hidden, inactive state.

This process of reactivation can result in the death of the infected cell or its recognition and elimination by the immune system. This can be done safely, preventing nearby cells from becoming infected, by activating the virus while the person with HIV is on ART.

An alternative strategy involves the use of drugs to drive the persisting virus into further hiding.

In this permanent state of latency, the virus remains dormant and can never be reactivated. While this approach does not eradicate the pool of infected cells, it would mitigate the risk of the virus re-emerging when ART is stopped.

Both these approaches are still under development so are not yet being used in the clinic.

Other approaches aim to enhance the immune system’s ability to control HIV, in the absence of antiretroviral therapy.

Recent small-scale clinical trials have shown that boosting immune function with HIV-specific antibodies or an HIV vaccine can allow approximately one third of participants to stop ART for a defined period and still keep the virus under control.

While these are very encouraging findings, larger trials are needed, along with a better understanding of why and how some participants can sustain virus control while others cannot.

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