Safety
and Antiviral Activity of PA-457, the First-in-class Maturation Inhibitor: A 10-Day
Monotherapy Study
PA-457
is the first compound in a new class of anti-HIV drugs called “maturation inhibitors.
Dr.
G. Beatty of the University of California at San Francisco (UCSF) presented
new data on the drug at the 45th Interscience
Conference on Antimicrobial Agents and Chemotherapy in
Washington, DC (December 16-19, 2005). In
this placebo-controlled, double blinded study, 33 HIV patients were given PA-457
orally once daily for 10 days (placebo, 25, 50, 100, or 200 mg). Study participants
had >/= 200 CD4 cells/mm3, HIV RNA 5,000-250,000 copies/mL,
and ARV naïve or >/= 12-weeks without therapy. Results 
Median CD4
count was 441 cells/microliter
and HIV RNA was 4.73 log 10 copies/mL at baseline.
The 100mg
and 200mg doses yielded significant reductions in HIV RNA load compared to placebo.
Median reductions
observed on day 11 were 0.03, 0.05, -0.17, -0.48, and -1.03 log10 for the placebo,
25, 50, 100, and 200 mg doses, respectively.
Patients
in the 100 and 200 mg dose groups with baseline viral loads <5log10 had median
reductions on Day 11 of -0.56, and -1.52, respectively.
Genotypic
data, available now for 21/33 patients, show no evidence
of resistance development to PA-457.
All doses
were generally safe and well tolerated with no Grade 3/4 laboratory abnormalities.
All adverse
experiences were mild to moderate.
One serious adverse event, of moderate severity,
was described as possibly related to treatment in a patient with a 5-year history
of poorly controlled hypertension and transient findings of a possible lacunar
CVA.
At the doses
studied, PA-457 demonstrated potent dose-related antiviral activity and were generally safe and well tolerated by study participants.
In
conclusion, the authors write, “These data support further development of PA-457
as a potential new treatment option for HIV infection.” 01/10/05 Reference
G
Beatty, J Lalezari and others. Safety and Antiviral
Activity of PA-457, the First-In-Class Maturation Inhibitor, in a 10-Day Monotherapy Study in HIV-1 Infected Patients. Abstract H-416d. Abstract LB-27. Abstracts of the 45th Interscience
Conference on Antimicrobial Agents and Chemotherapy. December 16-19,
2005. Washington, DC.
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