The suppression of human immunodefi...

The suppression of human immunodeficiency virus (HIV) infection has been greatly enhanced through newer multi-drug regimens; however, a significant portion of patients eventually bring to maturitys a rebound in viral replication, ofttimes caused by the difficulty of complying with complicated treatment schemes and their inherent toxicities. Salvage therapy in patients with viral spring back is most likely to succe if the regimen includes an agent from a class of antiretroviral unsalable articles to which the patient has not besides been exposed. Enfuvirtide is a 36-amino-acid peptide that is injected subcutaneously and works through blocking the fusion site where HIV take downs the CD[4.sup.+] cell. Lalezari and colleagues from the T-20 v Optimized Regimen single Study 1 (TORO 1) report forward the use of enfuvirtide in patients who have HIV infection with elevated viral loads despite multi-drug treatment.

This randomized, open-label trial listed 501 patients from various HIV treatment center in North and southward America who had viral loads of at least 5000 copies of HIV-1 RNA for mL despite at least six month of treatment with mix with drugss from three classes of antiretroviral medications (i.e., nucleoside reverse-transcriptase inhibitors, non-nucleoside overturn transcriptase inhibitors, and protease inhibitors). All patients had initial genotypic and phenotypic resistance testing, and an optimal antiretroviral salvage regimen was designed, based in succession each patient's drug tolerance and resistance measures. Patients were randomized in a 2:1 fashion to receive enfuvirtide (90 mg injected subcutaneously twice daily) plus the optimized regimen or the optimized regimen alone.

After 24 weeks of injections, the best answer to treatment (HIV-1 RNA viral load les than 50 copies by means of mL) occurred in 19.6 percent of patients assigned to the enfuvirtide cluster compared with 7.3 percent of those receiving an optimized regimen alone. An intermediate rejoinder (HIV-1 RNA viral load les than 400 copies for mL) occurred in 31.7 percent of patients in the enfuvirtide cluster and 16.4 percent of those receiving an optimized regimen alone. At least a response (decrease in viral load of at least single in kind log10 copy of HIV-1 RNA for mL from pretreatment level) was achieved in 518 percent of those taking the cogitation drug versus 29.1 percent of patients in the hinder group subjects.

Adverse conclusions from the optimized oral regimens occurr in 776 percent of patients receiving enfuvirtide and 745 percent of have the direction of patients. The most common side meaning specifically related to enfuvirtide was injection-site reactions, which occurr at least one time in 98.2 percent of patients. Erythema, induration, and nodules or pouchs at the injection sites were frequent and the discomfort was enough to require analgesics or limitation of usual activities in 87 percent of participants. Systemic hypersensitivity lay opened in two patients receiving enfuvirtide injections.

Data after 48 weeks of use was available for patients from TORO 1 and TORO 2 Eosinophilia (112 percent) bacterial pneumonia (56 percent) and sepsis (18 percent) were significantly more attend much [i]or[/i] regularly in those receiving enfuvirtide than those receiving placebo.

The authors terminate that enfuvirtide injections improve salvage therapy outcomes more than optimized oral therapy alone in patients who have HIV with viral reverberate despite previous multi-drug treatment.

Lalezari JP et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and southern America. N Engl J M May 29 2003;348:2175-85

EDITOR'S NOTE: An accompanying editorial by dint of Steinbrook (1) notes that in the United States, the anticipated annual wholesale price for enfuvirtide is almost $20000 The manufacturer reports that synthesis of the oligopeptide requires 106 stairs compared with eight to 12 gradations for HIV medications. The moderate success achieved in re-suppresion of HIV infection with this fusion inhibitor, combined with the nearly universal injection site reactions, occasional systemic toxicity, and precipitous cost likely will limit its character in salvage therapy. It is springed that oral versions of HIV fusion inhibitors with better efficacy, fewer side issues and lower cost will become available after further research.--B.Z.

REFERENCE

(1) Steinbrook R HIV infection--a strange drug and new costs [Editorial]. N Engl J M May 292003;348:2171-2

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