Recommendations for Treatment-experienced HIV Patients on Failing Regimens Containing Boosted Darunavir (Prezista/r)

Ritonavir-boosted darunavir (Prezista/r) has proven potent efficacy when used by heavily treatment-experienced patients with multiple protease inhibitor (PI)-associated resistance mutations. However, there are limited data on resistance patterns that emerge in patients failing darunavir/ritonavir and their effect on subsequent remaining PI treatment options.

In the current study, published in September 12, 2008 issue of AIDS, French researchers conducted an analysis of genotypic resistance mutations in 25 patients experiencing virological failure (> 200 copies/mL), both at baseline and after at least 3 months on a regimen containing darunavir/ritonavir (600/100 mg twice daily).

Results

• The study included 25 highly PI-experienced patients.

• Baseline median HIV RNA was 5 log10 copies/mL.

• Participants had a median of 13 total PI resistance mutations, 4 major PI mutations, and 3 darunavir-associated mutations.

• Median duration of viral replication with darunavir/ritonavir selective pressure was 34 weeks.

• Emergence of darunavir-associated-resistance mutations was observed in 18 of 25 patients (72%) of patients, at codons L89I/M/V (32%), V32I (28%), V11I (20%), I47V/A (20%), I54L/M (20%), L33F/I (16%) and I50V (16%).

• A high risk of darunavir resistance was observed in patients with 2 and 3 baseline darunavir-associated resistance mutations, and in those with more than 24 weeks of ongoing viral replication.

• According to 2007 ANRS (Agence Nationale pour la Recherche sur le SIDA) algorithm, isolates classified as susceptible to ritonavir-boosted tipranavir (Aptivus) decreased from 76% at baseline to 60% at failure.

• Isolates susceptible to darunavir/ritonavir decreased from 32% at baseline to 12% at failure.

In their conclusion, the study authors noted, "Emerging mutations observed after darunavir/ritonavir failure were those already described to impact the darunavir efficacy."

In closing, they recommended, first, to reconsider lowering the cut-off number of darunavir mutations to 2; second, to avoid keeping patients on a failing darunavir regimen for more than 24 weeks; and third, to examine the efficacy of using tipranavir after darunavir failure.

Saint Louis Hospital-APHP, Paris, France; Kremlin Bicêtre Hospital-APHP, Bicêtre, France; Necker Hospital-APHP, Paris, France; Mondor Hospital-APHP, Creteil, France; Louis Mourier Hospital-APHP, Colombes, France; Raymond Poincare-APHP, Garches, France.

9/09/08

Reference

C Delaugerre, J Pavie, P Palmer, and others. Pattern and impact of emerging resistance mutations in treatment experienced patients failing darunavir-containing regimen. AIDS 22(14): 1809-1813. September 12, 2008.

Related Articles

1. S Lambert-Niclot, P Flandre, A Canestr, and others. Factors associated with the selection of mutations conferring resistance to protease inhibitors (PIs) in PI-experienced patients displaying treatment failure on darunavir. Antimicrobial Agents and Chemotherapy 52(2): 491-496. February 2008.

2. I Pellegrin, L Wittkop, LM Joubert, and others. (ANRS Co3 Aquitaine Cohort). Virological response to darunavir/ritonavir-based regimens in antiretroviral-experienced patients (PREDIZISTA study). Antiviral Therapy 13(2): 271-279. 2008.

3. S de Meyer, T Vangeneugden, B van Baelen B, and others. Resistance profile of darunavir: combined 24-week results from the POWER trials. AIDS Research and Human Retroviruses 24(3): 379-388. March 2008.

4. R Ortiz, E Dejesus, H Khanlou, and others. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS 22(12):1389-97. July 31, 2008.