Monthly injectable ART - TLD

[Jim Allen]

A pre-clinical pharmacokinetic study indicates that injectable TLD could have the potential as a monthly injectable. Drug levels after four weeks in macaques maintained levels above IC90 (The drug concentration that will inhibit replication of 90% of HIV)

In Full: Monthly injectable ART: potential nanoformulation of tenofovir, 3TC and dolutegravir - Polly Clayden, HIV i-Base https://i-base.info/htb/46525

In Brief:

A novel long-acting injectable formulation of tenofovir, lamivudine and dolutegravir (TLD) sustained effective concentrations over four weeks in a macaque study.

Researchers from the University of Washington TLC-ART (Targeted, Long-acting and Combination Anti-Retroviral Therapy), are developing a long-acting TLD drug-combination

Five macaques were dosed 6.2, 5.1 10 mg/kg TLD-in-DcNP suspension and two (control) were dosed with free-soluble mixture TLD (dissolved in liquid but not using DcNP) – both by subcutaneous injection.

In four animals dosed with TLD-in-DcNP, peripheral blood mononuclear cells (PBMC) were isolated, in the 48– and 168–hour blood samples, and also analysed for drug content.

Tenofovir, 3TC and dolutegravir were detectable in plasma throughout a four-week period. By contrast, plasma drug levels in the animals receiving TLD-free dosage fell below detectable levels within three days.

The investigators concluded that these data show water-soluble tenofovir, 3TC, and water-insoluble dolutegravir combined into the single TLD-in-DcNP injectable provided four weeks plasma exposure in monkeys above detectable, measurable, and IC90-predicted levels.

[Jim Allen]

Additional information on long-lasting TLD treatment options being explored.

https://www.poz.com/article/longerlasting-hiv-meds-horizon
Longer-Lasting HIV Meds Are on the Horizon. An extended-release formulation of tenofovir, lamivudine and dolutegravir maintained effective drug levels for a month.