Journal Article

Improved Survival of HIV-1-Infected Patients with Progressive Multifocal Leukoencephalopathy Receiving Early 5-Drug Combination Antiretroviral Therapy

Hendel-Chavez, Houria, Lancar, Rémi, Gasnault, Jacques, Porte, Lydie, Costagliola, Dominique, Dulioust, Anne, Taoufik, Yassine, Lascaux, Anne-Sophie, Pakianather, Sophie, Mazet, Anne-Aurélie, Delfraissy, Jean-François, de Goer de Herve, Marie-Ghislaine

2011

Overview

Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery. All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008). The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death. ClinicalTrials.gov NCT00120367.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Adult / AIDS / Analysis / Anti-Retroviral Agents - therapeutic use / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / CD4 antigen / Cell survival / Confidence intervals / Cytokines / Demyelination / Deoxyribonucleic acid / Diagnosis / DNA / Drug therapy / Drugs / Encephalitis / Enfuvirtide / Female / Highly active antiretroviral therapy / HIV / HIV Envelope Protein gp41 - therapeutic use / HIV Fusion Inhibitors - therapeutic use / HIV infections / HIV Infections - drug therapy / HIV Infections - mortality / HIV Infections - virology / Human immunodeficiency virus / Humans / Immune clearance / Immunocompromised hosts / Immunological memory / Immunosuppressive agents / Infection / Infections / JC Virus - drug effects / JC Virus - pathogenicity / Leukoencephalopathy / Leukoencephalopathy, Progressive Multifocal - drug therapy / Leukoencephalopathy, Progressive Multifocal - mortality / Leukoencephalopathy, Progressive Multifocal - virology / Lymphocytes / Lymphocytes T / Male / Medical prognosis / Medicine / Middle Aged / NMR / Nuclear magnetic resonance / Patient outcomes / Patients / Peptide Fragments - therapeutic use / Polymerase Chain Reaction / Progressive multifocal leukoencephalopathy / Recovery / Ribonucleic acid / Risk analysis / Risk factors / RNA / Survival / T cell receptors / T cells / Therapy / Viral infections / Virus replication