A long-acting, injectable formulation of an HIV drug is demonstrated in mice in a study published in Nature Communications. A single injection maintained the required concentration of the drug to inhibit HIV replication in the blood and tissues of mice for at least a month.
Antiretroviral therapy has transformed HIV infection from a deadly condition to a chronic, manageable disease. However, patients need to adhere to a daily regimen of drugs as suboptimal adherence may lead to the development of resistant HIV strains. Drugs that require less frequent administration (for example, weekly, monthly or even bimonthly) would potentially be welcome alternative treatments.
Howard Gendelman and colleagues chemically modified dolutegravir, an antiretroviral medication, by attaching a long carbon chain and encapsulated the pro-drug (an inactive compound, which can be metabolized to produce an active drug) into a polymer. In mice, the final formulation showed high antiretroviral activity for more than four weeks.
Although some clinical trials of long-acting injectable HIV treatments are in progress, dolutegravir is already used by a number of patients. Additionally, the new formulation shows improved penetration into cells and tissues, where the virus forms reservoirs, and would require smaller injection volumes than other long-acting antiretroviral drugs currently undergoing investigation. Further studies will focus on the co-formulation of dolutegravir with other drugs and on the possibility of human trials, including both treatment of infected patients and protection of healthy individuals from infection.
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