enfuvirtide and Pneumonia

The introduction of enfuvirtide (FUZEON) represents an important advance in the treatment of therapy-experienced patients with HIV-1 infection. However, parenteral self-administration, and the advanced disease and antiretroviral experience of patients currently most needing enfuvirtide introduce unique usage considerations. Enfuvirtide has been shown to provide clinically relevant improvements in CD4 cell counts and reductions in HIV viraemia across all subgroups of treatment-experienced patients studied, including those taking few or no other active drugs. However, optimal outcome results from initiation when the CD4 cell count is above 100 x 10(6) cells/l and viraemia below 1 x 10(5) copies/ml, as part of a newly constructed third or fourth antiretroviral regimen in combination with one or two other antiretrovirals to which the virus remains sensitive. Resistance testing should be used where available to guide background drug selection. Where insufficient options for an effective background exist, enfuvirtide should still be considered and treatment undertaken with the aim of achieving an immunological or clinical response, despite the unlikelihood of a sustained virological outcome. Similarly, where there is no viable alternative treatment, enfuvirtide should be continued following virological failure wherever ongoing immunological or clinical benefit is discerned. Injection site reactions (ISRs) are common on enfuvirtide and will affect almost all patients. ISRs are manageable and seldom activity- or treatment-limiting. Bacterial pneumonia and systemic hypersensitivity reactions have also been reported uncommonly. A structured series of patient visits with a healthcare professional provides an atmosphere of ongoing training and support that may prevent 'injection fatigue', maintain adherence and minimise the incidence of ISRs. An initial investment in establishing such procedures can be expected to yield significant returns in patient confidence and benefit on enfuvirtide.

Topics: Clinical Trials, Phase III as Topic; Drug Hypersensitivity; Drug Resistance, Viral; Enfuvirtide; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; Humans; Injections, Intradermal; Patient Education as Topic; Peptide Fragments; Pneumonia; Randomized Controlled Trials as Topic; Treatment Outcome

Antiretroviral tolerability is a critical factor contributing to treatment outcome. The T-20 Versus Optimized Background Regimen Only (TORO) studies assessed the safety and efficacy of enfuvirtide in treatment-experienced HIV-1-infected patients.. A total of 997 patients were randomized at a 2:1 ratio to an optimized background antiretroviral regimen plus enfuvirtide (n = 663) or an optimized background regimen alone (control group; n = 334). Control patients could switch to enfuvirtide on virologic failure.. In total, 26.5% of patients randomized to enfuvirtide and 36.6% to the control group discontinued study treatment before week 48; the percentage of patients withdrawn for safety reasons (including adverse events [AEs], deaths, and laboratory abnormalities) was 14.0% in the enfuvirtide group and 11.6% in the control group. Injection site reactions (ISRs) occurred in 98% of enfuvirtide patients and led to treatment discontinuation in 4.4%. Treatment-related (defined as possibly, probably, or remotely) AE rates per 100 patient-years were lower with enfuvirtide (96.2) than in the control group (149.9); diarrhea, nausea, and fatigue, the most frequently reported AEs, were significantly less frequent with enfuvirtide than in the control group. Pneumonia was significantly more frequent in patients treated with enfuvirtide (6.7 vs. 0.6 events per 100 patient-years), although the incidence was within expected ranges for this population. Lymphadenopathy was also higher in enfuvirtide-treated patients (7.1 vs. 1.2 events per 100 patient-years) for control patients.. The addition of enfuvirtide to an optimized background regimen does not exacerbate AEs commonly associated with antiretrovirals. ISRs limited treatment in <5% of patients.

Topics: Adult; Anti-HIV Agents; Diarrhea; Drug Therapy, Combination; Enfuvirtide; Fatigue; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; HIV-1; Humans; Lymphatic Diseases; Nausea; Peptide Fragments; Pneumonia