EVG/FTC/TAF in Nanoparticles Suppresses HIV in Humanized Mice

Elvitegravir, emtricitabine and tenofovir alafenamide (EVG/FTC/TAF) subcutaneously injected as nanoparticles suppressed HIV replication in intravaginally infected humanized bone marrow-liver-thymus (hu-BLT) mice. Viral load remained undetectable three weeks after the last nanoparticle dose, according to the study.

Single-tablet EVG/cobicistat/FTC/TAF (Genvoya) is licensed in the United States for treatment of patients 12 years old or older who are starting antiretrovirals or switching from a stable, suppressive regimen. Researchers at Creighton University in Omaha, Nebraska, encapsulated EVG, FTC and TAF in nanoparticles and tested them against HIV in mice with functional human immune reconstitution.

The Creighton investigators used an oil-in-water emulsion technology to formulate nanoparticles loaded with TAF plus EVG, and they used water-in-oil-in-water technology to formulate nanoparticles loaded with FTC. The researchers randomly assigned six hu-BLT mice to treatment and six to no treatment. They intravaginally challenged all mice with virus from acutely infected people at a dose of 2.5 x 105 TCID50.

Starting three weeks after HIV challenge, treated mice received 200 mg/kg each of TAF and EVG and 100 mg/kg of FTC. Control mice received injections containing no antiretrovirals. Injections were given every two weeks for the first three doses, and a fourth dose was given one week after the third dose. The researchers measured viral load during weeks without injections.

Entrapment efficiency averaged 40% for TAF, 45% for EVG and 62% for FTC. After viral challenge and before the first injection, viral load averaged 12,000 copies/mL in treated mice and 170,000 copies/mL in control mice. Over the treatment period, viral load rose in control mice to about 1,000,000 copies/mL. In treated mice, average viral load rose above 100,000 copies/mL at the time of the first injection then began falling.

After four nanoparticle doses, all treated mice had an undetectable viral load (<800 copies/mL), while viremia averaged 1,700,000 copies/mL in control mice (P = .03). In treated mice, viral loads remained undetectable for three weeks after the last dose. All three drugs reached levels around or above 100 ng/g in lymph nodes and around 10 ng/g in liver and female reproductive tract tissue.

The Creighton team notes that this is the first proof-of-concept report of a preferred Department of Health and Human Services regimen encapsulated in nanoparticles and leading to undetectable viral loads after four subcutaneous doses.