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

Autor: C. Cometto, Silvia Fontana, Antonio D'Avolio, D. Aguilar, G. Di Perri, Andrea Calcagno, Stefano Bonora, A. Maiello, Anna Lucchini, I. Dal Conte, D. Gonzalez de Requena
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Microbiology (medical)
Oncology
Adult
Male
medicine.medical_specialty
Enfuvirtide
Human immunodeficiency virus (HIV)
Antiretroviral Therapy
HIV Infections
Pilot Projects
medicine.disease_cause
Enfuvirtida
administration /&/ dosage/therapeutic use
HIV Fusion Inhibitors
Antiretroviral Therapy
Highly Active
Internal medicine
medicine
Humans
Protease inhibitor (pharmacology)
Highly Active
drug effects/immunology
business.industry
virus diseases
HIV
General Medicine
Middle Aged
Viral Load
Therapeutic trial
Antiretroviral therapy
HIV Envelope Protein gp41
Peptide Fragments
CD4 Lymphocyte Count
drug therapy/virology
Infectious Diseases
Italy
Immunology
Reverse Transcriptase Inhibitors
Late presenters
Female
Adult
Antiretroviral Therapy
Highly Active
CD4 Lymphocyte Count
Female
HIV Envelope Protein gp41
administration /&/ dosage/therapeutic use
HIV Fusion Inhibitors
administration /&/ dosage/therapeutic use
HIV Infections
drug therapy/virology
HIV
drug effects/immunology
Humans
Italy
Male
Middle Aged
Peptide Fragments
administration /&/ dosage/therapeutic use
Pilot Projects
Reverse Transcriptase Inhibitors
administration /&/ dosage/therapeutic use
Viral Load
business
medicine.drug
Popis: 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.Very late presenters (CD450/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 load50 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.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 count200/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 load50 copies/ml at week 24 was comparable.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.
Databáze: OpenAIRE
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