Cidofovir in AIDS-associated progressive multifocal leukoencephalopathy: A monocenter observational study with clinical and JC virus load monitoring

Abstract

A monocenter observational study was conducted to determine the clinical and virological effects of cidofovir added to highly active anti-retroviral therapy (HAART) in AIDS-associated progressive multifocal leukoencephalopathy (PML). Exposure to other anti-viral drugs or late initiation of cidofovir were exclusion criteria. Of the 53 consecutive patients with virologically proven PML admitted at the NeuroAIDS Unit of Bicêtre Hospital between May 1996 and July 2000 and having received HAART with or without cidofovir, 46 met the inclusion criteria. Cidofovir was initiated in most cases on compassionate grounds. The 22 patients treated with HAART only (HAART group) were compared to the 24 patients treated with HAART and cidofovir (CDV group). Survival, neurological outcome assessed by the expanded disability status scale (EDSS), and monitoring of the JC virus (JCV) load in CSF were investigated prospectively. At baseline (date of initiation or intensification of HAART), both groups were similar regarding CD4 cell count, plasma HIV load, CSF JCV load, EDSS, and demographic features. Both groups had similar response to HAART in terms of plasma HIV load and CD4 cell count. At month 6, CSF-JCV load was below the detection level in 8 out of 24 (33%) patients from the CDV group and 7 out of 18 (39%) patients from the HAART group (P = 0.71). One-year cumulative probability of being alive was 62% in the CDV group and 53% in the HAART group (P = 0.72). However, an additional benefit with respect to survival was observed in patients who were given cidofovir after adjustment to the following baseline variables (CSF-JCV load, CD4 cell count, and EDSS). Despite the addition of cidofovir to HAART, no significant benefit had been observed in neurological outcome, particularly in patients with an early worsening.

Smoothened Agonist Reduces Human Immunodeficiency Virus Type-1-Induced Blood-Brain Barrier Breakdown in Humanized Mice

“…Major clinical trials, including Cidofovir - a nucleoside analog effective against CMV48, mementin - N-methyl-D-aspartate receptor (NMDA) antagonist, widely used for treatment of neurodegenerative disorders49, CPI-1189, Selegiline and Minocycline - drugs with antioxidant properties505152 while safe and well tolerated, failed to achieve significant neuroprotective benefits in persons with HIV. Disappointing outcome of these drugs clearly indicate that targeting individual factors like; oxidative stress or inflammation alone is not sufficient to control a multifaceted disorder like HAND.…”

Recommendations on the algorithms for drug choice and risk management plan in the treatment of patients with remitting multiple sclerosis with natalizumab

“…Специфической терапии ПМЛ не существует [23,35]. Курсы высокоактивной антиретровирусной терапии (цитофовир, цитарабин) в большинстве случаев оказались неэффективными [9,10,14,34,40,55]. Большинству пациентов с ПМЛ был проведен курс ПФ, реже осуществляли иммуноабсорбцию (ИА) с целью удаления натализумаба из циркуляции крови и восстановления иммунитета [46].…”

JC Polyomavirus (JCV) and Monoclonal Antibodies: Friends or Potential Foes?

“…CDV is an acyclic nucleotide phosphonate analog of deoxycytosine monophosphate; due to its inhibitory action on DNA polymerase, its effect on JCV has been tested with contradictory results. The low efficacy of CDV may reflect poor penetration, and severe side effects have been reported [98, 99]. Recently, a lipid derivative of CVD (a hexadecycloxypropyl lipid conjugate of CVD, called CMX001) was found to reduce JCV replication, with no significant toxicity in cell cultures derived from human fetal brain, suggesting that it could be a promising candidate for the treatment of PML [100].…”