Treatment with HAART improves the prognosis of HIV-positive patients with the neurological disorder progressive multifocal leukoencephalopathy (PML), according to a Spanish study published in the 15th April 2003 edition of Clinical Infectious Diseases. Nearly two thirds of patients remained alive over two years after diagnosis with the disease, with many experiencing a cure. However, there were still high rates of mortality, with patients with a CD4 cell below 100 cells mm3 at greatest risk of death.
PML is a disease of the central nervous system. It is normally seen in patients with poor immune function, and prior to the introduction of HAART, a diagnosis with PML was invariably followed by death, normally within four to six months.
Data about the impact of HAART on the prognosis of patients with PML are limited. Accordingly, Spanish investigators conducted a retrospective analysis of the medical records of 118 HIV-positive patients diagnosed with PML after the introduction of HAART, to determine the factors associated with survival.
Investigators gathered information on the patients’ demographic characteristics, year of HIV diagnosis, previous AIDS-defining illnesses, CD4 cell count and HIV viral load. PML-related data were also obtained, including date and method of diagnosis, symptoms and treatment. Finally, data on the use of HAART were collected.
The study patients had an average age of 36. The overwhelming majority had injecting drug use as their risk factor for HIV (68.6%). Average CD4 cell count at baseline was 85 cells/mm3 (range 40 - 160) and viral load was 4.85 log10. PML was the first AIDS-defining illness in almost two thirds of patients, and PML developed in a third of patients after the initiation of HAART.
Amongst the 39 patients who were diagnosed with PML after starting anti-HIV treatment, nine experienced treatment failure, with six patients having poor treatment adherence. PML developed in ten other patients as a consequence if immune reconstitution, on average six weeks after starting HAART. In the remaining 20 patients, it was not possible to attribute PML to either treatment failure or immune reconstitution.
Anti-PML therapy, consisting of the anti-CMV drug cidofovir, was administered to 44 patients (a little over 37%) and corticosteroids were given to eight patients.
Seventy-five patients (63.6% of the cohort) were alive 2.2 years after diagnosis with PML. There were 36 PML-related deaths (30.5% of sample), and these occurred on average twelve weeks after diagnosis with PML. Seven patients died of conditions not associated with PML.
Neurological function in survivors was categorised as a cure or improvement in 33 (44%) and as stabilisation or worsening in 40 (53%). Two patients could not be evaluated.
CD4 cell count was found to be the only factor which was predictive of prognosis. Amongst the patients who died, 71% had a CD4 cell count below 100 cells/mm3. Amongst survivors, 47% had a CD4 cell count below 100 cells/mm3.
Based on CD4 cell count, the investigators estimated an average survival time of over four years (235 weeks) for patients with CD4 cell counts above 100 cells/mm3, and over three years (177 weeks) for patients with CD4 cell count below 100 cells/mm3.
The investigators note that even when HAART was provided, approximately a third of patients with PML died. However, improvement in neurological function was found in about 50% of survivors.
Delayed reconstitution of the immune system was considered the most likely reason why 20 patients with neither treatment failure nor an immune reaction died of PML despite starting HAART.
Treatment with cidofovir was not found to have an effect on prognosis. The investigators conclude that “one-third of patients with PML died despite receiving HAART and ... neurologic function improved in approximately one-half of survivors. A CD4 cell count of 3 was associated with a higher mortality rate.”
Further information on this website
Progressive multifocal leukoencephalopathy - Overview
Predicting prognosis with viral load
Predicting prognosis with CD4 count
Prognosis - Factsheet
Cidofovir - Overview
Berenguer J et al. Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy. Clinical Infectious Diseases 36 (electronic edition), 2003.