The new boosted protease inhibitor darunavir has already proven to be more powerful than other boosted protease inhibitors when taken by highly treatment-experienced individuals. (The drug, formerly known as TMC 114, has been released under the trade name Prezista in the United States) Combined results from three related clinical trials have now confirmed that darunavir is equally effective, regardless of whcih protease inhibitor has been used previously.
Much of the data on darunavir are drawn from several ongoing multi-site trials conducted by Tibotec, the drug manufacturer. For the purposes of this study, data from three of these randomised trials – POWER 1, 2 and 3 – was combined. These three trials all studied similar groups of people: participants were on failing regimens, with viral loads over 1000 copies/mL. They also had experience with nucleoside analogues, non-nucleoside analogues (NNRTIs) and protease inhibitors (PIs), and had developed at least one PI resistance mutation.
On starting the study, all participants received a background antiretroviral regimen that was optimised by resistance testing, plus 600mg darunavir and 100mg ritonavir twice daily. The new combinations may or may not also have included enfuvirtide (T-20, Fuzeon); none contained any NNRTIs.
Darunavir effectiveness against protease inhibitor-resistant HIV
The study looked at virological response to the new drug regimen after 24 weeks. Specific comparisons were made between those whose previous (failing) regimen had contained tipranavir (TPV), lopinavir (LPV), and fosamprenavir (fAPV).
Results were very similar for the study overall, and the three PI-specific groups:
- In the overall study (458 people): average viral load drop of 1.74 log; 42% became undetectable.
- In the TPV group (51 people): average viral load drop of 1.64 log; 44% became undetectable.
- In the LPV group (192 people): average viral load drop of 1.72 log; 40% became undetectable.
- In the fAPV group (74 people): average viral load drop of 1.66 log; 42% became undetectable.
Darunavir compared to other protease inhibitors
The study also compared the effectiveness of boosted darunavir to other, ‘control’ PIs (CPIs). In the set of participants studied (131 on darunavir-containing regimens, 124 on CPIs), darunavir performed very impressively: 45% and 12%, respectively, achieved viral loads of less than 50 copies/ml after 24 weeks. Responses were, unsurprisingly, better in those who showed genotypic susceptibility to at least one CPI at baseline (24%, vs. 7% in those resistant to all CPIs). Among the CPIs, fosamprenavir was the most successful, leading to undetectable viral loads in 16% of those taking it.
Researchers concluded that darunavir ‘showed greater HIV RNA reductions and CD4 cell count increases over the [control PIs (CPIs)] used by the control group, regardless of CPI used, type of boosting (single or double RTV-boosted PI regimen), and baseline susceptibility’, and that ‘the PI-based regimen at screening did not affect the subsequent virologic response to TMC114/r 600/100 mg bid plus [an optimised background regimen] after 24 weeks of treatment.’
Lefebrve E et al. Impact of use of TPV, LPV and (f)APV at screening on TMC114/r virologic response in treatment-experienced patients in POWER 1, 2 and 3. Forty-Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract H-1387, 2006.