AEGiS-CATIE: TreatmentUpdate: New protease inhibitors: ABT-378 and '141'

TreatmentUpdate: New protease inhibitors: ABT-378 and '141'

TreatmentUpdate 76. 9(2): 8-9; March, 1997
Sean Hosein

This article is based on information presented at the 4th Conference on Retroviruses and Opportunistic Infections in Washington, DC, January 22-26, 1997.

ABT-378

Abbott Labs, which also makes ritonavir, has developed a drug called ABT-378 that in experiments with HIV-infected cells and animals is:

* 10 times more powerful than ritonavir

* active against HIV which is resistant to ritonavir

* is able to increase the concentration of ritonavir (when used together).

Low doses of ritonavir also increase the concentration of ABT-378. As well, HIV that is resistant to ABT-378 is still sensitive to saquinavir.

?141?

Glaxo-Wellcome is testing the protease inhibitor 141W94 (commonly called ?141? and formerly called VX-478) and the ?nuke? 1592U89 (commonly called ?1592?) together. Nine HIV-infected subjects, half of whom had:

* 233 CD4+ cells

* a viral load of about 66,000 copies

and who never received a protease inhibitor, received ?141? ? 900 mg twice daily together with ?1592? ? 300 mg twice daily for 4 weeks.

Results

Viral load fell to about 660 copies and CD4+ cell counts rose between 60 and 105 cells. Symptoms of toxicity included diarrhea, nausea and rash. Two subjects left the study because of nausea (1 subject) and rash (1 subject).

REFERENCES:

1. Kumar GN, Dykstra J, Jayanti V and Denissen JF. Potent inhibition of the in vitro human liver microsomal metabolism of the HIV-1 protease inhibitor ABT-378 by ritonavir - potential for positive drug interaction. Poster 211.

2. Schooley RT and the 141W94 international study group. Preliminary data from the phase I/II study on the safety and antiviral efficacy of the combination of 141W94 plus 1592U89 in HIV-infected patients with 150 to 400 CD4+ cells/mm3. Oral presentation LB3.

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