enfuvirtide and Drug-Hypersensitivity

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

The present study investigated the effect of enfuvirtide cross-reactive glycoprotein 41 (gp41) antibody on the efficacy or safety of enfuvirtide in patients participating in 1 of 2 24-week phase 3 clinical trials (T-20 vs. optimized regimen only [TORO] 1 and TORO 2). Serum samples from human immunodeficiency virus-infected patients receiving enfuvirtide plus optimized background (OB) and from patients receiving OB only were evaluated for enfuvirtide cross-reactive gp41 antibodies. Most patients had detectable levels of antibody at baseline; 78% of patients treated with enfuvirtide plus OB had a > or =30% decrease in level of antibody, compared with 43% of patients treated with OB only. Baseline antibody status did not influence virological responses to enfuvirtide-containing treatment. Favorable virological responses were more common among patients who experienced a > or =30% decrease from baseline than among those who experienced either an increase or a lesser decrease. A decrease in virus load correlated with a decrease in level of antibody. Safety was unaffected by the presence of positive antibody at any time point or change in level of antibody. There was no evidence that enfuvirtide cross-reactive gp41 antibody affects the efficacy or safety of enfuvirtide.

Topics: Adolescent; Adult; Cross Reactions; Drug Hypersensitivity; Enfuvirtide; HIV Antibodies; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; HIV-1; Humans; Injections, Subcutaneous; Pain; Peptide Fragments; RNA, Viral; Skin; Viral Load

Enfuvirtide is beneficial in patients with limited treatment options. We report this case to highlight the possibility of a delayed hypersensitivity reaction as an important potential side-effect of enfuvirtide treatment. A highly antiretroviral treatment-experienced man was commenced on a new regimen containing enfuvirtide. Prophylaxis for Pneumocystis jirovecii pneumonia was started using trimethoprim/sulphamethoxazole (TMP-STX) simultaneously. Ten days later, he developed a maculopapular rash on the chest and abdomen without any systemic features. Both enfuvirtide and TMP-STX were discontinued. Re-introduction of enfuvirtide occurred in a hospital setting. Before re-challenge, haemodynamic observations were stable. The rash re-appeared involving the whole body 5 hours post-dose and was associated with fever (temperature 38.4), nausea and a presyncopal episode. Hypersensitivity to this drug occurred immediately post-dose in phase III trials. Enfuvirtide is a useful drug in those with reduced drug options. The possibility of delayed hypersensitivity has not been reported previously.

Topics: Antiretroviral Therapy, Highly Active; Drug Hypersensitivity; Enfuvirtide; Exanthema; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; HIV-1; Humans; Hypersensitivity, Delayed; Male; Middle Aged; Peptide Fragments

Topics: Adult; Desensitization, Immunologic; Drug Hypersensitivity; Enfuvirtide; Female; HIV Envelope Protein gp41; HIV Fusion Inhibitors; Humans; Long-Term Care; Peptide Fragments; Treatment Outcome

Topics: Desensitization, Immunologic; Drug Hypersensitivity; Enfuvirtide; Follow-Up Studies; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; Humans; Male; Middle Aged; Peptide Fragments; Risk Assessment

We report a case of successful, rapid desensitization to enfuvirtide after a hypersensitivity reaction in a man with highly drug-resistant human immunodeficiency virus type 1 infection. The patient was desensitized in a monitored intensive care unit and tolerated the rapid desensitization protocol without any serious adverse effects. This case illustrates the ability to safely desensitize patients with limited treatment options who require enfuvirtide therapy.

Topics: Adult; Drug Hypersensitivity; Enfuvirtide; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; HIV-1; Humans; Male; Peptide Fragments; Remission Induction