| |
Clinical and Virological Correlates of Longer Survival in AIDS-Associated Progressive Multifocal Leukoencephalopathy A. DE LUCA*, M. L. GIANCOLA, A. AMMASSARI, S. GRISETTI, M. G. PAGLIA, M. GENTILE, A. CINGOLANI, R. MURRI, A. D'ARMINIO MONFORTE, and A. ANTINORI.
Clin. Malattie Infettive, Univ. Cattolica, IRCCS "L. Spallanzani," Roma, and Malattie Infettive e Tropicali, Univ. di Milano, Italy PML is highly lethal and invalidating. Some patients show longer survival with HAART.
Objective:To analyze the association of clinical, therapeutical, virological and immunological variables with survival in pts with AIDS-related PML.
Design: Analysis of consecutive HIV+ pts with PML from 3 tertiary care centers (diagnosis: histological and/or virological). Group I: pts treated with ARA-C and antiretroviral mono- or bitherapy; group II: pts treated with HAART (with PI); group III pts treated with HAART+cidofovir. Quantitation of CSF JCV-DNA (linear range 3.0-6.3 log). Survival analysis by Kaplan-Meier, using Cox regression.
Results: First 56 pts: 23 group I, 22 group II, 11 group III. At baseline: 79% M, 80% IDU, 11% hetero, 9% MSWM, 44% previous AIDS, median age = 36 y, Karnofsky = 50, CD4 = 35/mmc, plasma HIV-RNA = 4.58 log, CSF HIV-RNA 3.23 log, JCV-DNA in CSF = 3.30 log. Median survival from diagnosis was 75 days (400 in pts with HAART). 2 months after therapy, 16% of pts showed clinical improvement/stability. 44% reached undetectable JCV-DNA in CSF and 35% HIV-RNA in CSF <80 copies/ml. Associated with longer survival were JCV-DNA load in CSF of 3 log or less (P at log rank = 0.05), undetectable JCV-DNA at follow up (P=0.01), no progression during the first 2 months (P=0.0001), use of HAART before and after PML onset (P= 0,005 and P= 0.0001, respectively). Clinical presentation, VL in plasma and CSF at baseline and follow up, CD4, cidofovir, previous AIDS, gender, age and transmission category were not associated with survival. HAART after the onset of PML (P=0.019) and a lack of progression during the first 2 months of therapy (P=0.001) were independently associated with survival. JCV-DNA level in CSF of 3 log or less was associated with lack of progression during the first 2 months (P=0.004, Fisher's exact test).
Conclusion: Survival of AIDS-related PML is strongly influenced by HAART and associated to the control of JC virus load in CNS rather than to the inhibition of systemic or CNS replication of HIV. Patients surviving longer remain clinically stable.
Key Words: HAART, JC virus, PML
|
