Ritonavir-boosted
Darunavir (Prezista) Is Well Tolerated by Treatment-experienced Patients in POWER
1, 2 and 3 Trials Both
the 24- and 48-week results of the POWER 1 and 2 trials demonstrated significant
virological and immunological improvement in treatment-experienced patients using
the newly approved protease
inhibitor (PI) darunavir (Prezista, formerly TMC-114) co-administered with
ritonavir, compared with control arms. Similar efficacy was seen in an analysis
of a large group receiving open-label darunavir (POWER 3).
A pooled analysis,
presented at the XVI International AIDS Conference in Toronto, assessed the clinical
safety of the recommended dose of darunavir/ritonavir
for treatment-experienced patients, 600/100 mg twice daily (BID), in POWER 1,
2, and 3.
Patients were PI-, NRTI-, and NNRTI-experienced, with 1 primary
PI mutation at baseline. Adverse events were evaluated in all POWER 1, 2, and
3 participants using twice daily 600/100 mg darunavir/ritonavir in their initial
regimen (de novo; n = 458), and in POWER 1 and 2 patients using comparator
PIs (n = 124).
Results 
The majority of reported adverse events were mild to moderate (grade 1-2) in severity.
The frequency
of serious adverse events was 15% for darunavir/ritonavir versus 14% for comparator
PIs.
No
individual serious adverse event occurred in more than 1% of patients.
11 patients taking darunavir/ritonavir died, but none of these deaths were considered
at least possibly related to darunavir/ritonavir treatment.
Frequency of discontinuations and the most common adverse events are shown in
the tables below.
Discontinuations
|
|
POWER 1-3 darunavir/r
600/100mg BID de novo (n = 458) |
POWER 1 and
2 comparator PI (n = 124) |
|
All discontinuations (%) |
11 |
81 |
|
Due to adverse events (%) |
4 |
5 |
|
Due to virological failure (%) |
3 |
67 |
Most
Common Treatment-associated Adverse Events Occurring in at Least 10%
|
Diarrhea (%) |
16 |
28 |
|
Nausea (%) |
12 |
13 |
|
Nasopharyngitis (%) |
12 |
11 |
|
Headache (%) |
11 |
20 |
Most
Common Grade 2-4 Adverse Events Occurring in at Least 2%
|
Diarrhea (%) |
3 |
3 |
|
Vomiting (%) |
2 |
2 |
|
Headache (%) |
2 |
2 |
Conclusion
According
to the study authors, "[D]arunavir/ritonavir is generally well tolerated
by treatment-experienced patients." Further, they noted, "The incidence
of diarrhea with darunavir/ritonavir was lower than with comparator PIs."
They concluded that, "[D]arunavir/ritonavir is expected to provide a valuable
HIV therapy option." Centro
de Referência e Treinamento DST/AIDS, Mariana-São Paulo, Brazil,
Chalucet Hospital, Toulon, France, University of California, San Francisco, United
States, Tibotec BVBA, Mechelen, Belgium, Tibotec Inc., Yardley, United States. 08/29/06 References
J Valdez Madruga,
A Lafeuillade, G Beatty, and others. TMC114/r is well tolerated by treatment-experienced
patients in power 1, 2 and 3: integrated clinical safety analysis. XVI International
AIDS Conference. Toronto, August 13-18, 2006. Abstract TUPE0062. J
M Molina, C Cohen, C Katlama, and others. TMC114/r in treatment-experienced HIV
patients in POWER 3: 24-week efficacy and safety analysis. XVI International AIDS
Conference. Abstract TUPE0060.
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