Infection

, Volume 40, Issue 1, pp 69–75 | Cite as

Short-term additional enfuvirtide therapy is associated with a greater immunological recovery in HIV very late presenters: a controlled pilot study

  • S. Bonora
  • A. Calcagno
  • C. Cometto
  • S. Fontana
  • D. Aguilar
  • A. D’Avolio
  • D. Gonzalez de Requena
  • A. Maiello
  • I. Dal Conte
  • A. Lucchini
  • G. Di Perri
Brief Report
First Online:
Received:
Accepted:

Abstract

Objectives

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/mm3), 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+/mm3 (12–37) and a percentage of 3.3 (1.7–7.1) in the ENF arm, and 16 CD4+/mm3 (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/mm3, p = 0.04), with 70% of enfuvirtide intakers versus 12.5% of controls who achieved a CD4+ cell count >200/mm3 (p = 0.01). At 48 weeks, patients in the ENF arm had CD4+ cell counts higher than controls (251 vs. 153cells/mm3, p = 0.04) and were also found to be faster in reaching a CD4 cell count over 200/mm3: 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.

Keywords

HIV Advanced naïve Enfuvirtide Immunological recovery 
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Notes

Conflict of interest

A.C. received travel grants, speaker’s honoraria, and consultancy fees from Abbott. S.B. received travel grants, speaker’s honoraria, and consultancy fees from Abbott. G.D.P. received travel grants, speaker’s honoraria, and consultancy fees from Abbott, and consultancy fees from Roche. Other authors declare no potential conflict of interest.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • S. Bonora
    • 1
  • A. Calcagno
    • 1
    • 2
  • C. Cometto
    • 1
  • S. Fontana
    • 1
  • D. Aguilar
    • 1
  • A. D’Avolio
    • 1
  • D. Gonzalez de Requena
    • 1
  • A. Maiello
    • 1
  • I. Dal Conte
    • 1
  • A. Lucchini
    • 1
  • G. Di Perri
    • 1
  1. 1.Department of Infectious DiseasesUniversity of TorinoTurinItaly
  2. 2.Clinica Universitaria di Malattie Infettive (CUIp)TurinItaly

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