Switch from Enfuvirtide to Raltegravir in Virologically Suppressed Multidrug-Resistant HIV-1-Infected Patients: A Randomized Open-Label Trial

• Published in: Clinical infectious diseases Vol. 49; no. 8; pp. 1259 - 1267
• Main Authors: De Castro, Nathalie, Braun, Joséphine, Charreau, Isabelle, Pialoux, Gilles, Cotte, Laurent, Katlama, Christine, Raffi, François, Weiss, Laurence, Meynard, Jean-Luc, Yazdanpanah, Yazdan, Delaugerre, Constance, Madelaine-Chambrin, Isabelle, Aboulker, Jean-Pierre, Molina, Jean-Michel
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.10.2009; University of Chicago Press; Oxford University Press
• Subjects: Adult; AIDS; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretrovirals; Antiviral agents; Biological and medical sciences; Blood plasma; Drug resistance; Drug Resistance, Multiple, Viral; Experimentation; Female; Genetic mutation; HIV; HIV 1; HIV Envelope Protein gp41 - adverse effects; HIV Envelope Protein gp41 - therapeutic use; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - isolation & purification; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infections; Infectious diseases; Male; Medical sciences; Middle Aged; Peptide Fragments - adverse effects; Peptide Fragments - therapeutic use; Pharmacology. Drug treatments; Plasma; Pyrrolidinones - adverse effects; Pyrrolidinones - therapeutic use; Raltegravir Potassium; Ribonucleic acid; RNA; RNA, Viral - blood; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; Immunopathology; Antiretroviral agent; Peptides; AIDS; Immune deficiency; Fusion inhibitor; Infection; Integrase inhibitor; Enfuvirtide; Viral disease; Multiple resistance; Antiviral; Raltegravir
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/605674

Background. Among patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection, salvage regimens including enfuvirtide have demonstrated sustained efficacy. Because of reluctance to use subcutaneous injections, raltegravir may be an alternative to replace enfuvirtide within a suppressive regimen. We conducted a prospective, randomized, open-label trial to compare the antiviral efficacy and safety of a switch to raltegravir with the efficacy and safety of continuing enfuvirtide. Methods. A total of 170 patients with multidrug-resistant HIV-1 infection and plasma HIV-1 RNA levels <400 copies/mL who were receiving enfuvirtide-based regimens were randomized 1:1 to maintain enfuvirtide or to switch to raltegravir. The primary efficacy end point was the cumulative proportion of patients with virologic failure, defined as a confirmed plasma HIV-1 RNA level ⩾400 copies/mL, over 24 weeks. The secondary end points mainly involved safety. Results. The switch to raltegravir was non-inferior to the maintenance of enfuvirtide, with virologic failure rates of 1.2% in both treatment arms in the intention-to-treat analysis (d=0.01%; 95% confidence interval, −6.7 to 6.8) and 1.2% and 0%, respectively, in the on-treatment analysis (d=1.22%; 95% confidence interval, −5.6 to 8.1). At week 24, 88%–89% of patients in both arms had plasma HIV-1 RNA levels <50 copies/mL. No significant CD4 cell count changes occurred in either arm. Grade 3–4 adverse events and laboratory abnormalities were uncommon and were not different between the treatment arms. Conclusion. A switch to raltegravir was safe, well tolerated, and virologically non-inferior to the maintenance of enfuvirtide in patients infected with multidrug-resistant HIV-1 infection who were receiving suppressive antiretroviral therapy. Clinical trials registration. NCT00454337.