Lightening the Load: Looking for a Cure for HIV

HIV is a wide-reaching public health problem, with more than 37 million individuals infected worldwide. Current antiretroviral therapy (ART) has a varying array of uses, ranging from HIV treatment to pre-exposure prophylaxis. For patients with HIV who have access to medication, daily antiretroviral drugs hinder viral replication and prevent the patient’s death from AIDS. Unfortunately, our current drug therapy for HIV is not curative, and relies on consistent treatment to suppress the level of the virus.

An article published in a recent issue of the journalDrugs In Contextdescribes some current strategies under investigation to cure HIV, including 2 approaches: (1) a sterilizing cure or (2) a functional cure for individuals living with HIV.

Sterilizing cures attempt to remove the virus completely from the host. Current sterilizing cure possibilities consist of the ‘shock and kill,’ and gene editing and stem cell transplantation strategies.

The ‘shock and kill’ method uses HDAC inhibitors, such as valproic acid, to purge the integrated virus from HIV reservoirs, making it transcriptionally active. Once the virus is active, current drug therapy combined with specific cytotoxic CD8+ T cells can eliminate it. However, despite early indication that this approach could work, this method still needs refinement.

The gene editing and stem cell transplantation method models the case of the ‘Berlin patient,’ a patient who had HIV and became HIV-negative after receiving a hematopoietic stem cell transplantation. Many researchers have attempted to reproduce these results, but sadly none have been successful.

Functional cures use the immune system to keep the virus at an undetectable level without the need for ongoing ART. Such strategies include early treatment initiation and intensification of ART and broadly neutralizing antibodies (bNAbs).

Early initiation and intensification plays on the idea that early, prolonged ART therapy may allow some patients to achieve prolonged remission without the need for constant medication. However, even in instances where patients start on early ART, permanent remission rarely occurs.

The discovery of bNABs has opened pathways in therapeutic innovation. In early clinical trials, treatment with bNABs reduced HIV RNA in patients. One main set back was the potential for rapid development of HIV resistance to these antibodies.

Drug therapy against HIV has drastically advanced since the disease was discovered in the '80s, with many therapies giving patients the chance to live relatively normal lives. As research into this disease continues, perhaps one day soon we will find a cure.

Reference

Pham HT, Mesplède T. The latest evidence for possible HIV-1 curative strategies.Drugs Context.2018 Feb 21;7:212522.