Modified Antiviral Drug Could Cure HIV

Altering the chemical structure of an antiviral drug may help it penetrate HIV viral reservoirs and could expedite the public health goal of curing HIV, according to a study published by Nature Communications.

In the new study, the authors used a psychiochemical scheme to change the properties of dolutegravir and inserted it into nanocrystals.

The resulting drug crystals were found to circulate throughout the body and target HIV viral reservoirs, which are notoriously difficult to access. Even when a patient’s viral load is nearly undetectable, viral reservoirs of HIV persist and can multiply when antivirals are not taken.

This approach was also found to extend the life of dolutegravir, increase the capability to reach viral reservoirs, and reduce viral growth, according to the study. The chemically-altered dolutegravir was able to reach viral reservoirs in the lymph nodes, bone marrow, intestines, and spleen.

Significantly, the drug crystals were non-toxic, did not disintegrate with temperature changes, and demonstrated long-term stability, according to the study. The authors also noted that organs and functionality did not appear to be affected by this treatment.

The crystals are coated with parts of fat and are able to navigate through the protective membrane of cells to be stored in macrophages for weeks, according to the study. Once inside the cells, the drug was released from the crystal as a prodrug, which was broken down into an active drug. The active formulation was then circulated to cells and tissue storage.

"The strength of this system is that it not only can be effective in improving HIV care and prevention but can be applied to many classes of drugs beyond HIV, such as drugs used to treat cancer, other infectious diseases and degenerative diseases that affect the brain,” said co-lead researcher Benson Edagwa, PhD.

These findings suggest that chemically altering dolutegravir may expedite an HIV cure, which has been out of reach thus far.

“The new products can optimize HIV restrictive growth so that strategies that may eradicate viral infection would be successful,” said co-lead researcher Howard Gendelman, PhD.