title: Safety and efficacy of enfuvirtide in combination with darunavir-ritonavir and an optimized background regimen in treatment-experienced human immunodeficiency virus-infected patients: the below the level of quantification study.
abstract: Enfuvirtide is the first fusion and entry inhibitor approved for use for the treatment of human immunodeficiency virus (HIV) type 1 infection and as such represents a novel class of agents. For the population of patients experienced with three antiretroviral classes, enfuvirtide provides an additional option for treatment. This prospective, open-label, 24-week, single-arm trial assessed the efficacy and safety of enfuvirtide (90 mg injected subcutaneously twice daily) in combination with darunavir-ritonavir (600/100 mg administered orally twice daily) in triple-antiretroviral-class-experienced adults failing their current regimen. The primary efficacy endpoint was the proportion of participants with plasma HIV RNA loads of <50 copies/ml. Other virological and immunological measures were also evaluated, as were the effects of the baseline viral coreceptor tropism and darunavir phenotype sensitivity scores on the outcomes. At week 24, 60.3%, 72.5%, and 84.0% of 131 participants achieved viral loads of <50 copies/ml and <400 copies/ml and a change from the baseline load of > or =1 log(10) copies/ml, respectively. A baseline viral load of < or =5 log(10) copies/ml was a significant predictor of achieving a viral load of <50 copies/ml at 24 weeks; however, neither background genotype sensitivity nor darunavir phenotype sensitivity was a significant predictor of the achievement of viral loads of <50 copies/ml. Although these findings are limited by the relatively small numbers of participants with darunavir susceptibility changes of > or =10-fold, they suggest that combining enfuvirtide and darunavir-ritonavir with an optimized background regimen in triple-class experienced participants naïve to these agents can result in positive virological and immunological responses regardless of most baseline parameters.
authors.affiliation: Orlando Immunology Center, 1701 N. Mills Avenue, Orlando, FL 32803, USA. edejesus@oicorlando.com
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gottlieb
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Gathe
authors.forename: Michael L
authors.initials: ML
authors.lastname: Greenberg
authors.forename: Carol Jean
authors.initials: CJ
authors.lastname: Guittari
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Zolopa
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069454:Darunavir; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D010446:Peptide Fragments; D013449:Sulfonamides; D000077560:Enfuvirtide; D019438:Ritonavir; D000069454:Darunavir