HIV: Is a cure possible with immunotherapies?

ARTs for HIV treatment are highly effective, but rebounds occurs after medicine discontinuation. This article looks at developing treatment options in this field.

Immunotherapies show promising results

The latent HIV reservoir causes rebound

People who are HIV-positive and treated with antiretroviral therapy (ART) quickly achieve a significant reduction in viral load. However, after discontinuation of the medication, a rebound occurs quickly, which is caused by the latent HIV reservoir. This reservoir arises because ARTs do not eradicate the virus, but reduce it. Research to cure HIV therefore targets the latent reservoir.

Two different approaches

The therapies that could be considered, either target an eradication of the virus or a reduction of the viral load. In the latter case, immune responses or modulations then take effect to keep the infection under control. This could be a pathway to achieve remission.

Immunotherapies could lead to remission in exactly this way, by acting on cytotoxic T cells, NK cells and antibodies. A combination of mechanisms of action affecting multiple arms of the immune system is also conceivable.

Interface between vaccination and cure

But it is not only research into possible therapies that lead to remission that aims to achieve long-lasting immune surveillance. Vaccine research is also concerned with these effects. Thus, both research arms can complement each other and provide starting points for possible further studies.

Long-lasting effect versus continuous therapy

To achieve HIV remission, a long-lasting effect of a therapeutic agent is crucial. However, continuous administration of drugs is less effective in achieving eradication or remission.

The timing of therapy induction as well as possible combinations of active agents could also play a decisive role here.

Broadly neutralising antibodies (bNAb) in the focus of science

bNAbs were originally obtained from infected individuals, but are now available for clinical use.

In studies, the combination of two different bNAbs infused three times has resulted in up to 30 weeks of viral suppression during a break in ART. Whether bNAbs improve T-cell function is also a focus of HIV research.

Regarding the timing of therapy initiation, a randomised controlled trial showed that patients who received the bNAb 3BNC117 at the time of ART induction achieved better viral control, particularly those with a 3BNC117-sensitive viral variant. One patient achieved virus undetectable status for over four years after stopping ART.

Combination brings advantages in animal models

Besides bNAbs, therapeutic stimulation of toll-like receptors is also an approach in the treatment of HIV. In animal models, the combination of bNAbs and TLR-7 agonists showed good remission rates. Whether this can be transferred to humans, however, remains to be seen.

Conclusion for medical practice

The search for an eradication therapy for HIV has identified several substances that can help. In addition to bNAbs, there are other therapeutics in development that still need to be investigated in trials. Eradication is currently rather unlikely even with bNAb treatment, but good results up to long-lasting remission have been described if bNAb induction takes place at the time of ART therapy.

Session: Approaches for HIV cure and vaccine research. Thomas RASMUSSEN, Aarhus University Hospital, Immunotherapies towards an HIV cure, AIDS 2022, 31.7.2022.