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Session 75
Poster Abstracts Neuropathogenesis: Therapy and Clinical Studies Friday, 1:30 - 3:30 pm Hall D |
Background: Despite improved survival with HAART,
AIDS-related progressive multifocal leukoencephalopathy (PML) causes death in many patients
and, in those who survive, significant disability.
Case series and an uncontrolled trial reached different conclusions regarding
the effectiveness of cidofovir (CDV) for PML
treatment in patients on HAART. We pooled data from published cohorts to
identify the effect of CDV on survival and neurological outcomes.
Methods: Data were obtained from 6 cohorts of HIV+
PML diagnosed after 1995 treated with HAART with or without CDV. Baseline, or
date of diagnosis, was defined as date of first abnormal neuroimaging.
To address potential survival bias, we also considered baseline in patients receiving CDV as the date drug was started. Study outcomes were time
to PML-related death (Cox’s models) and odds of 12-month severe disability
(Rankin score ≥ 4)
Results: We identified 372 patients: 64% confirmed by pathology or JC virus DNA
detection in CSF; median calendar year of baseline was 1999 (range 1996 to 2003);
age 38 years (14 to 73), 80% male; 57% injecting drug users (IDU); 33% prior
CDC class C; median CD4 73/µL (0 to 1191), plasma HIV RNA (n = 305) 4.97 log10
(1.69 to 6.56); CSF JCV DNA (n = 140) 3.72 log10 copies/mL (1.00 to 7.71); Karnofsky 50
(20 to 100). Before PML diagnosis, 32% took only NRTI, 35% HAART, 19% both. Of the 372 patients, 185 (50%) received CDV for a
median of 5 cycles (range 1 to 68, total n = 1590 cycles). During 465 patient-year
follow-up, 168 PML-related deaths occurred (36.1 of 100 patient years).
Estimated 1-year survival was 0.56 (95% CI: 0.50 to 0.61). Unadjusted predictors of
survival were higher baseline Karnofsky and CD4,
lower CSF JCV DNA levels, diagnosis after 1996 and cohort, but not the use of
CDV or proven vs presumptive diagnosis. In a
multivariate analysis stratified by cohort, CDV was independently associated
with survival considering follow up from baseline (HR for death 0.71; 0.50 to 0.99,
p = 0.05), but not when baseline was
defined as date of CDV initiation (HR 0.91; 0.65 to 1.28). Among 188 survivors,
74 (39%) showed a severe 12-month Rankin disability score. Independent
predictors of severe disability were lower baseline CD4 and Karnofsky
but not use of CDV.
Conclusions: In a metaanalysis of
HIV+ HAART-treated PML, CDV was significantly associated with
improved survival when follow up was started from PML diagnosis, but not when
it started at time of CDV initiation. Moreover, CDV use did not influence
severity of disability. New treatments for PML are urgently needed.
Keywords: PML; HAART; cidofovir
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