Speaker: Beth L. Nordstrom, PhD, Epidemiologist, Ingenix Epidemiology, Aburndale, Massachusetts

In a large population of patients with influenza, treatment with oseltamivir (Drug Tamiflu, Hoffman-LaRoche Ltd.) was associated with a significant reduction in the risk of pneumonia. Several clinical studies showed that oseltamivir was up to 92% effective in preventing influenza in adolescents, adults, and elderly adults when it was taken once daily for seven days. These studies suggested that the risk of pneumonia and other sequelae of influenza might be decreased in patients who used this agent.

To determine the risk of pneumonia, the frequency of antibiotic dispensing, and hospitalization rates among influenza patients in a real-world setting, investigators conducted a retrospective cohort study using medical and prescription claims data for members of United Healthcare, a large U.S. health insurer, and a source population from the Ingenix Research Database. The cohort included patients one year of age or older with an insurance claim diagnosis of influenza between December 1, 1999, and March 31, 2002, and who either had taken oseltamivir generic or who had not taken any antiviral medication. The researchers also assessed the rate of dispensing of antibiotics or hospitalization within 30 days after an influenza diagnosis. Separate analyses were performed, according to the number of outcomes (exposed vs. unexposed) in patients receiving oseltamivir and in patients who had not taken osel-tamivir, across three age ranges, as shown in the chart in the next column.

In the 13- to 59-year-olds, the risk of pneumonia was reduced by 19%; in fact, the decreased risk was most dramatic in the youngest and oldest age groups. In the patients aged one to  years, the risk was reduced by 66%. In patients 60 years of age and older, the risk was reduced by 59%. Finally, in these two age groups, the incidence of required antibiotic therapy and hospitalization was also decreased.

Anidulafungin in HIV-Negative Patients with Esophageal Candidiasis

Speaker: Jennifer A. Schranz, MD, Director, Clinical Research, Vicuron Pharmaceuticals, King of Prussia, Pennsylvania

Anidulafungin (Vicuron Pharmaceuticals), a novel echino-candin antifungal antibiotic with potent in vitro and in vivo activity against Candida species, including azole-resistant and camphotericin B-resistant organisms, was as effective and as well tolerated as fluconazole (Diflucan generic, Pfizer) in HIV-nega-tive patients with esophageal candidiasis. This therapy gives physicians one more option for patients with fluconazole intolerance as well as a benefit of no dose adjustments required for patients with renal or hepatic impairment or for those taking concomitant medications.

Initially, a phase 3, randomized, double-blind, double-dummy comparative trial was conducted from April 2001 through October 2002 from sites in South Africa, Thailand, Argentina, and the U.S. to compare the efficacy and safety of anidulafungin versus fluconazole in patients with esophageal candidiasis. Of 601 patients, 300 were assigned to receive anidulafungin 100 mg IV on the first day and 50 mg IV daily, and 301 were to receive fluconazole 100 mg orally each day. Treatment lasted for 14 to 21 days for patients who remained symptom-free for seven days.

The primary method of efficacy analysis was a comparison of endoscopic response in evaluable per-protocol patients at the end of therapy (EOT). Secondary efficacy analyses included (1) the clinical response (a successful response was the absence or improvement of symptoms compared with baseline values) and (2) the mycological response (a successful response was proven or presumed eradication of baseline Candida species).

Of the patients who agreed to HIV testing, 114 of 136 patients in the anidulafungin group (83.6%) and 123 of 143 in the fluconazole group (86.9%) were HIV-positive. At the EOT for the overall study, the endoscopic success rate was 97.2% with anidulafungin (242 of 249 patients) and 98.8% (252 of 255 patients) with fluconazole. Anidulafungin was found to be statistically non-inferior to fluconazole. High rates of microbiological success were also seen for anidulafungin (86.7%) and fluconazole (90.9%).

For the documented HIV-negative subgroup from the large clinical trial, 19 anidulafungin patients and 18 fluconazole patients were in the clinically evaluable EOT population. Fungal infections in those patients were caused by immuno-suppression resulting from cytotoxic therapy for cancer or preventing transplanted organ rejection; the overuse of antibiotics; the excessive use of corticosteroids; or invasive surgical techniques in high-risk individuals. Most of these patients had moderate-to-severe symptoms of disease.

At the EOT, the clinical response rate and the endoscopic success rate were 100% for both anidulafungin and fluconazole treatment groups of patients. The mycological response rates in the EOT population were 81.8% (9 of 11 patients) taking anidulafungin and 90.9% (10 of 11 patients) taking fluconazole.

Early Treatment with Enfuvirtide Found to Be Most Beneficial

Speaker: Calvin J. Cohen, MD, Research Director, Community Research Initiative of New England and Clinical Instructor, Harvard Medical School, Boston, Massachusetts

The early use of enfuvirtide (Fuzeon®, Roche/Trimeris) with an optimized-background (OB) regimen in treatment-experienced HIV-infected patients results in better outcomes, including significantly lower virological failure rates and markedly less loss of active background agents, when compared with regimens that do not contain enfuvirtide; it also preserves future drug options.

These findings were derived from a new analysis of the TORO (T-20 [Fuzeon®] vs. Optimized Regimen Only) studies, two randomized phase 3 clinical trials that assessed the efficacy and safety of enfuvirtide plus an OB regimen of antiretroviral agents (ARVs) versus an OB regimen alone in 995 triple-class experienced HIV-infected patients.

The patients were randomly assigned, in a 2:1 fashion; 661 received enfuvirtide plus an OB regimen and 334 received an OB regimen alone. The analysis was designed to explore the development of resistance and antiretroviral efficacy of initial or subsequent regimens in treatment with and without enfu-virtide.
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Results from these exploratory and retrospective analyses of the TORO studies indicated that 33% of patients who did not receive enfuvirtide in their regimen at the beginning of the TORO trials developed resistance to at least one active therapeutic option. In contrast, only 13% of those who began their treatment with an enfuvirtide-based regimen at the initiation of the TORO studies experienced a loss of at least one active treatment option after 48 weeks because of virological failure.

In addition, 32% of the patients receiving an enfuvirtide-based regimen from the outset of the study achieved un-detectable levels of HIV-1 RNA (less than 400 copies/ml) compared with 22% of the patients receiving a non-enfuvirtide-based regimen. This finding represents a significant difference favoring the use of an enfuvirtide-based regimen.