Improved survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy receiving early 5-drug combination antiretroviral therapy.

Abstract

BACKGROUND:

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.

METHODS AND FINDINGS:

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).

CONCLUSIONS:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00120367.

• Authors: Jacques Gasnault, Dominique Costagliola, Houria Hendel-Chavez, Anne Dulioust, Sophie Pakianather, Anne-Aurélie Mazet, Marie-Ghislaine de Goer de Herve, Rémi Lancar, Anne-Sophie Lascaux, Lydie Porte, Jean-François Delfraissy, Yassine Taoufik, ANRS 125 Trial Team
• Journal: PloS one (PLoS One) Vol. 6 Issue 6 Pg. e20967 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21738597 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Retroviral Agents
• HIV Envelope Protein gp41
• HIV Fusion Inhibitors
• Peptide Fragments
• Enfuvirtide

Topics

• Adult
• Anti-Retroviral Agents (therapeutic use)
• Enfuvirtide
• Female
• HIV Envelope Protein gp41 (therapeutic use)
• HIV Fusion Inhibitors (therapeutic use)
• HIV Infections (drug therapy, mortality, virology)
• Humans
• JC Virus (drug effects, pathogenicity)
• Leukoencephalopathy, Progressive Multifocal (drug therapy, mortality, virology)
• Male
• Middle Aged
• Peptide Fragments (therapeutic use)
• Polymerase Chain Reaction