Once-Weekly and Once-Monthly HIV Meds in the Pipeline: Studies From ICAAC 2012
Two new HIV drugs in development that show promise for less frequent dosing were previewed at ICAAC 2012 in San Francisco.
One of the drugs, a fusion inhibitor named albuvirtide, could make once-a-week HIV medication a reality. Results from two small Chinese studies demonstrated the general safety and effectiveness of albuvirtide.
The first study followed 54 HIV-infected, treatment-naive individuals in Beijing, all of whom had a viral load above 5,000 copies/mL and a CD4+ cell count above 250 cells/mm3. The group consisted of 39 men and 15 women with a median age of 37.5. Each participant was either treated with a single dose of albuvirtide or a placebo. Two participants discontinued treatment during the study.
The second study followed 12 HIV-infected, treatment-naive men who have sex with men. Half of the group (median age 35.5) was given multiple albuvirtide doses of 160 mg, while the other half (median age 26.5) received multiple doses of 320 mg. The doses were given on days 1, 2, 3, then 8 and 15.
Albuvirtide is administered intravenously, while the only approved fusion inhibitor, enfuvirtide (T-20, Fuzeon), is administered subcutaneously. And, unlike enfuvirtide, albuvirtide does not require twice-daily dosing.
In the single-dose study, albuvirtide's plasma half-life averaged 11 days. Participants tolerated albuvirtide well: there were no injection-site reactions and no serious adverse events. Elimination kinetics were linear. Albuvirtide monotherapy suppressed plasma viremia for 6 to 10 days.
In the multiple-dose study, there were no serious adverse events and no drug-related adverse events of any kind. There were no injection site reactions through the 5 doses. No anti-albuvirtide antibodies could be detected in plasma for up to 42 days.
While these early results indicate albuvirtide is well tolerated and can suppress HIV for up to 10 days, further research is needed in a larger study population with more long-term indications.
The second drug in development, an integrase inhibitor currently known as S/GSK1265744 (or simply "744"), was analyzed in two studies, and showed a potential to control HIV for up to one month with a single dose taken either orally or through long-acting parenteral injection.
The first study looked into the effectiveness of 744 and its potential interactions with raltegravir (Isentress) and elvitegravir (GS 9137, JTK-303).
Cell studies showed generally low-level resistance with S/GSK1265744, a long-acting integrase inhibitor that may control HIV with a single shot administered once a month. The findings suggest a high barrier to resistance, limited or low potential for cross-resistance to raltegravir and elvitegravir. [...]
In an earlier study, 744 showed strong antiviral activity at an oral dose of 30 mg once daily, suppressing viral load by a median 2.6 log10 copies/mL at treatment day 11. A nanosuspension formulation of 744 had a half-life of 21 to 50 days after a single intramuscular or subcutaneous injection, a result indicating that once-monthly dosing may be possible.
The second study showed that S/GSK1265744 was well tolerated and could be taken with rilpivirine (Edurant) without negative interactions. Still, as with any drug in early-stage development, further research needs to be conducted to test the long-term efficacy and safety of 744 in larger study groups.
[Editor’s note: An earlier version of this article incorrectly stated that enfuvirtide is administered intravenously, when in fact it is administered subcutaneously. The article has been corrected to reflect this.]