Outcomes for treatment-experienced patients receiving 'salvage therapy' that includes the protease inhibitor darunavir (Prezista) are equal to, or even better, than those seen in clinical trials, Swiss investigators report in the online edition of HIV Medicine.
After 48 weeks of treatment, viral load was detectable in 20% of Swiss patients, compared to 55% of those in the POWER studies that lead to the licensing of darunavir. Of the 130 patients in this study, 37 were receiving T-20 (enfuvirtide, Fuzeon) at baseline, of whom 22 stopped the drug while taking darunavir. Eleven of these patients switched to raltegravir (Isentress).
But the majority of patients in this study did not receive a new antiretroviral drug class – either an entry inhibitor or integrase inhibitor – when they started darunavir.
“Salvage therapy with darunavir is as successful in clinical practice as it has been in clinical trials,” comment the investigators.
A number of antiretroviral drugs have recently become available that provide important treatment options for treatment-experienced patients with drug-resistant HIV.
One of these drugs is darunavir, which is usually boosted by a small dose of ritonavir (Norvir). In clinical trials, 45% of highly treatment-experienced patients had an undetectable viral load after 48 weeks of therapy with the drug in combination with an optimised regime of other anti-HIV drugs. Even better outcomes were seen in patients with moderate treatment experience, and those starting HIV therapy for the first time.
Resistance to darunavir is uncommon, but is associated with previous therapy with the protease inhibitors amprenavir (Telzir) and saquinavir (Invirase).
Despite the promising outcomes of patients treated with darunavir in clinical trials, there is little information about the safety and effectiveness of the drug in routine clinical practice.
Therefore, Swiss investigators monitored 130 treatment-experienced patients who received darunavir as a component of 'salvage therapy' for up to 72 weeks. All had experienced a sustained increase in viral load when taking other combinations, and all the patients had experience of therapy with the main three classes of antiretrovirals.
The patients had an average age of 47, and had been living with diagnosed HIV infection for a median of 16 years. Consistent with this long duration of infection, most (81%) had received treatment with either mono or dual therapy, and since then had experienced virologic failure when taking a median of three protease inhibitor-based combinations.
Typically there was a considerable time period between the development of virologic failure on an earlier treatment (median 6.6 years) and starting therapy with darunavir. This meant that many patients developed drug-resistant virus, and only 42% had virus that was fully susceptible to darunavir when they initiated therapy with the drug.
Nevertheless, most of the patients were in reasonable health. Their median CD4 cell count was 250 cells/mm3, 43% had been diagnosed with AIDS, and 22% were co-infected with hepatitis C virus.
Patients were followed for a median of 45 weeks. A total of 22 patients stopped therapy with the drug after a median of 22 weeks. However, twelve subsequently restarted darunavir. Six patients stopped the drug because of side-effects, including fat redistribution, liver toxicity and diarrhoea.
One patient died. His death was not related to treatment with darunavir, and was recorded as due to “HIV disease resulting in other bacterial infections”. In addition, four patients were diagnosed with an AIDS-defining condition.
Viral load was measured using one of three different assays.
Virologic failure – defined as viral load never being suppressed to undetectable or rebounding after falling below this level – occurred in between 18% and 29% of patients. The highest failure rate was seen using Amplicor assay.
Many of the patients (between 48 and 56% depending on the testing assay) whose viral load was not effectively suppressed had baseline resistance to darunavir.
Older age was associated with an increased chance of viral load suppression with a darunavir containing regimen. Being a woman was associated with a poorer outcome, as was baseline viral load, poor adherence and the presence of virus that was resistant to darunavir.
‘The patients receiving darunavir as part of salvage therapy in this study were not dissimilar to the highly treated patients receiving darunavir in the POWER trials,” comment the investigators.
They conclude: “When used for salvage therapy, darunavir can achieve a similar efficacy and tolerability to that seen in clinical trials.”
However, they note that virologic failure during amprenavir or saquinavir therapy, and the number of previous unsuccessful protease inhibitor regimens, were associated with less effective control of HIV when taking darunavir. They recommend that doctors should keep this in mind “when choosing a salvage regimen”.
Young J et al. Efficacy, tolerability and risk factors for virological failure of darunavir-based therapy for treatment-experienced HIV-infected patients: the Swiss HIV Cohort Study. HIV Med, online edition, DOI: 10.1111/j.1468-1293.2010.00885, 2010 (click here for abstract)