596   Prospective Pilot Study of Cidofovir for HIV-Associated Progressive Multifocal Leukoencephalopathy (PML).

C. M. Marra*¹, N. Rajicic², D. E. Barker³, B. Cohen⁴, and D. Clifford⁵and the ACTG 363 Team.
¹Univ. of Washington, Seattle;²Harvard Univ., Boston, MA;³Cook County Hosp. and⁴Northwestern Univ., Chicago, IL; and⁵Washington Univ., St. Louis, MO.

Background:There is no proven treatment for PML. ACTG 363 was a prospective non-randomized pilot study of cidofovir for HIV-associated PML.

Methods:Subjects had symptoms of PML for<90 days. 5 mg/kg IV cidofovir was given at week (wk) 0 and 1 wk later, then every 2 wks adjusted for renal function. Follow-up continued to 24 wks.

Study procedures were: neurological exam (wk 0, then every 4 wks); MR (wks 0, 8, 24); CD4 count and plasma HIV-1 RNA (wks 0, 8, 16, 24); intraocular pressure (IOP) (wk 0 and<48 hrs of cidofovir infusion). Primary outcome was change in neurological exam score between wks 0 and 8. Exact statistical tests were used.

Results:Entry characteristics of 24 subjects (19 men) were (median [range]): 38 yrs (29—52), CD 4 cells 62/ml (4—339), plasma HIV-1 RNA 2,941 copies/ml (48—433,105), Karnofsky 60 (30—90); mean (SD) baseline neurological exam score 8.04 (+9.81, n = 23). 12 subjects died. Median survival was 7.5 wks (2—24). 5 subjects discontinued treatment due to proteinuria (n = 1) or>50% drop in IOP (n = 4). At entry, 5 subjects took no antiretrovirals (ARVs), 7 were on the same ARV regimen for>13 wks, 9 began a combination regimen<12 wks before, and 3 added agents to an existing regimen<12 wks before entry. Fewer subjects on the same ARV regimen for>13 wks died compared to those not taking ARVs, beginning a new regimen, or adding to an existing regimen, but this difference was not significant (2/7 vs. 10/17, P = 0.52). Median baseline HIV-1 RNA was higher (49,499 vs. 722, P = 0.05) and median CD4 was lower (25.5 vs. 153.5, P = 0.0009) in subjects who died. Mean change in neurological exam score at 8 wks was -0.15+8.57 (n = 13), and was not associated with change in HIV-1 RNA or CD4 or with ARV status. 13 subjects had MR scans at 8 wks. MR abnormalities improved in 7 and worsened in 6. MR change was not associated with change in neurological exam score.

Conclusions: Overall, cidofovir did not prolong PML survival beyond what has been reported without treatment. Higher CD4 and lower plasma HIV-1 RNA at baseline were significantly associated with longer survival.