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Fuzeon plus an active PI provides maximal HIV suppression in treatment-experienced patients

Patients previously treated with three classes of antiretrovirals can achieve maximal viral suppression when starting a regimen of Enfuvirtide ( Fuzeon ) in combination with an active boosted protease inhibitor ( PI ) and other anti-HIV drugs.

New study data were presented at the 12th annual Conference on Retroviruses and Opportunistic Infections ( CROI ).

These new studies add to the growing body of evidence that support a powerful treatment strategy for treatment-experienced patients - building upon findings from the Fuzeon pivotal trials, TORO-1 and TORO-2.

" The goal of HIV treatment is to achieve maximum suppression of the virus - for both patients who are starting an antiretroviral regimen for the first time, and those who are treatment-experienced," said Joseph Eron, Jr., at the University of North Carolina, Chapel Hill. " The data presented at CROI are encouraging because they show that this goal is attainable in triple-class experienced patients. Multiple independent studies are showing that the majority of triple-class experienced HIV-positive patients achieve maximal response when an active PI-containing regimen is paired with Fuzeon. "

Investigators reported results of a 24-week phase IIB study of an investigational boosted protease inhibitor, TMC-114/Ritonavir, in triple-class experienced patients.
Of those who received Fuzeon and TMC-114/Ritonavir for the first time, two-thirds ( 67 percent; 18/27 ) achieved undetectable levels of HIV at 24 weeks ( defined as less than 50 copies/mL of HIV in the blood ) compared to one-third ( 37 percent; 10/27 ) of patients who received TMC-114/Ritonavir without Fuzeon as part of their background regimen. Almost half ( 47 percent ) of patients in the trial received Fuzeon.

Integrated results of the phase III RESIST trials of another investigational boosted protease inhibitor, Tipranavir, in triple-class experienced patients were also presented at CROI. In the trial, the greatest treatment response was seen in patients treated with Fuzeon and Tipranavir/Ritonavir, along with other anti-HIV drugs.
Despite extensive prior treatment and resistance to multiple drugs, more than two-thirds ( 70 percent ) of study participants using Fuzeon and Tipranavir/Ritonavir for the first time in their regimens achieved a treatment response ( defined as at least a 1 log drop in HIV levels from baseline ) after 24 weeks of therapy.

Fuzeon is the first and only fusion inhibitor for the treatment of HIV. Unlike other HIV drugs that work after HIV has entered the human immune cell, Fuzeon works outside the CD4 cell, blocking HIV from entering the cell. For this reason, Fuzeon is effective in treatment-experienced patients who have developed resistance to other anti-HIV drugs, though patients may still develop resistance to Fuzeon.

Injection site reactions ( ISRs ) are the most common adverse events associated with Rnfuvirtide.
ISRs occurred in 98% of patients studied and 4% discontinued Enfuvirtide due to ISRs.
Signs/symptoms may include pain and discomfort, hardened skin, redness, bumps, itching and swelling. Eleven percent of patients had local reactions that required analgesics or limited usual activities.

An increased rate of bacterial pneumonia was observed in subjects treated with Enfuvirtide in the Phase III clinical trials compared to the control arm. It is unclear if the increased incidence of pneumonia is related to Enfuvirtide use. Patients with HIV infection should be carefully monitored for signs and symptoms of pneumonia. Risk factors for pneumonia included low initial CD4 cell count, high initial viral load, intravenous drug use, smoking and a prior history of lung disease.

Systemic hypersensitivity reactions have been associated with Enfuvirtide therapy and may recur on rechallenge. Hypersensitivity reactions have included individually and in combination: rash, fever, nausea and vomiting, chills, rigors, hypotension and elevated serum liver transaminases. Other adverse events that may be immune mediated and have been reported in subjects receiving Enfuvirtide include primary immune complex reaction, respiratory distress, glomerulonephritis and Guillain-Barre syndrome.

The events most frequently reported in patients receiving Enfuvirtide plus an optimized background regimen were diarrhea ( 32% ), nausea ( 23% ) and fatigue ( 20% ). These events were seen at a lower incidence in patients taking a Enfuvirtide-based regimen compared to those receiving an optimized background regimen without Enfuvirtide when taking into account the uneven number of patients in each arm and the length of time they are in that arm. As measured in number per 100 patient-years, the incidence was: diarrhea ( 38 per 100 patient-years in subjects receiving Enfuvirtide-based regimens vs. 73 per 100 patient-years in patients who did not receive Enfuvirtide ), nausea ( 27 vs. 50, respectively ) and fatigue ( 24 vs. 38, respectively ).

Source: Trimeris, 2005