Cidofovir added to HAART improves virological and clinical outcome in AIDS-associated progressive multifocal leukoencephalopathy.

Abstract

OBJECTIVES:

To analyse the virological and clinical efficacy of cidofovir combined with highly active antiretroviral therapy (HAART) in AIDS-related progressive multifocal leukoencephalopathy (PML).

DESIGN:

Multicentre observational study of consecutive HIV-positive patients with histologically or virologically-proven PML. Group A, 26 patients treated with HAART; group B, 14 patients treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and alternate weeks thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR.

RESULTS:

Baseline virological, immunological and clinical characteristics were homogeneous between the groups. In one case cidofovir was discontinued because of severe proteinuria. There was no significant difference in HIV RNA responses and changes in the number of CD4 cells between group A and B. After 2 months of therapy, five out of 12 (42%) patients from group A and seven out of eight (87%) from group B reached undetectable JC virus DNA in the CSF (Chi-square P = 0.04); moreover, 24% of group A and 57% of group B patients showed neurological improvement or stability (P = 0.038). One-year cumulative probability of survival was 0.67 with cidofovir and 0.31 without (log-rank test, P = 0.01). Variables independently associated with longer survival were the use of cidofovir, HAART prior to the onset of PML, a baseline JC virus DNA load in CSF < 4.7 log10 copies/ml, and a baseline Karnofsky performance status > or = 60.

CONCLUSIONS:

In AIDS-related PML, cidofovir added to HAART is associated with a more effective control of JCV replication, with improved neurological outcome and survival compared with HAART alone.

• Authors: A De Luca, M L Giancola, A Ammassari, S Grisetti, A Cingolani, M G Paglia, A Govoni, R Murri, L Testa, A D Monforte, A Antinori
• Journal: AIDS (London, England) (AIDS) Vol. 14 Issue 14 Pg. F117-21 (Sep 29 2000) ISSN: 0269-9370 [Print] England
• PMID: 11061646 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• DNA, Viral
• Organophosphonates
• Organophosphorus Compounds
• RNA, Viral
• Cytosine
• Cidofovir

Topics

• Adult
• Anti-HIV Agents (adverse effects, therapeutic use)
• Antiretroviral Therapy, Highly Active
• CD4 Lymphocyte Count
• Cerebrospinal Fluid (virology)
• Cidofovir
• Cytosine (adverse effects, analogs & derivatives, therapeutic use)
• DNA, Viral (analysis)
• Drug Therapy, Combination
• Female
• HIV (isolation & purification)
• HIV Infections (complications, drug therapy)
• HIV Seropositivity (complications, drug therapy)
• Humans
• JC Virus (isolation & purification)
• Leukoencephalopathy, Progressive Multifocal (complications, drug therapy)
• Male
• Middle Aged
• Organophosphonates
• Organophosphorus Compounds (adverse effects, therapeutic use)
• Proteinuria (chemically induced)
• RNA, Viral (analysis)
• Treatment Outcome