title: Short-term additional enfuvirtide therapy is associated with a greater immunological recovery in HIV very late presenters: a controlled pilot study.
abstract: OBJECTIVE
  To evaluate whether the addition of enfuvirtide to standard highly active antiretroviral therapy (HAART) could confer immunovirological benefits in human immunodeficiency virus (HIV)-infected very late presenters. The current study is an open comparative therapeutic trial of standard protease inhibitor (PI)-based HAART ± additional enfuvirtide in treatment-naïve deeply immunologically impaired HIV-positive patients.
  
  
  METHODS
  Very late presenters (CD4 <50/mm(3)), without tuberculosis and neoplasms, were alternatively allocated to two nucleoside reverse transcriptase inhibitors (NRTIs) and lopinavir/ritonavir without (control arm, CO) or with (ENF arm) enfuvirtide 90 mg bid. Enfuvirtide was administered until the achievement of viral load <50 copies/ml and for at least 24 weeks. The primary objective was the magnitude of CD4+ cell recovery at 6 months. HIV RNA was intensively monitored in the first month, and, thereafter, monthly, as for CD4+ cell count and percentage, clinical data, and plasma drug concentrations.
  
  
  RESULTS
  Of 22 enrolled patients (11 per arm), 19 completed the study (10 in the ENF arm). Baseline CD4+ cell counts and % were comparable, with 20 CD4+/mm(3) (12-37) and a percentage of 3.3 (1.7-7.1) in the ENF arm, and 16 CD4+/mm(3) (9-29) and a percentage of 3.1 (2.3-3.8) in the CO arm, respectively. The baseline viral load was also comparable between the two arms, with 5.77 log10 (5.42-6) and 5.39 log10 (5.06-6) in the ENF and CO arms, respectively. Enfuvirtide recipients had higher CD4+ percentage at week 8 (7.6 vs. 3.6%, p = 0.02) and at week 24 (10.7 vs. 5.9%, p = 0.02), and a greater CD4+ increase at week 24 (207 vs. 134 cells/mm(3), p = 0.04), with 70% of enfuvirtide intakers versus 12.5% of controls who achieved a CD4+ cell count >200/mm(3) (p = 0.01). At 48 weeks, patients in the ENF arm had CD4+ cell counts higher than controls (251 vs. 153cells/mm(3), p = 0.04) and were also found to be faster in reaching a CD4 cell count over 200/mm(3): 18 (8-24) versus 48 (36-108) weeks (p = 0.01). Viral load decay at week 4 was greater in the ENF arm (-3 vs. -2.2 log, p = 0.04), while the proportion of patients with viral load <50 copies/ml at week 24 was comparable.
  
  
  CONCLUSIONS
  In this pilot study, the addition of enfuvirtide to a lopinavir-based HAART was shown to be associated with a significantly faster and greater immunological recovery in newly discovered HIV-positive patients with very low CD4+ cell counts. Induction strategies using an enfuvirtide-based approach in such subjects warrant further investigation.
authors.affiliation: Department of Infectious Diseases, University of Torino, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Turin, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bonora
authors.forename: A
authors.initials: A
authors.lastname: Calcagno
authors.forename: C
authors.initials: C
authors.lastname: Cometto
authors.forename: S
authors.initials: S
authors.lastname: Fontana
authors.forename: D
authors.initials: D
authors.lastname: Aguilar
authors.forename: A
authors.initials: A
authors.lastname: D'Avolio
authors.forename: D
authors.initials: D
authors.lastname: Gonzalez de Requena
authors.forename: A
authors.initials: A
authors.lastname: Maiello
authors.forename: I
authors.initials: I
authors.lastname: Dal Conte
authors.forename: A
authors.initials: A
authors.lastname: Lucchini
authors.forename: G
authors.initials: G
authors.lastname: Di Perri
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D000077560:Enfuvirtide; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D018894:Reverse Transcriptase Inhibitors; D000077560:Enfuvirtide