Despite HAART, People with HIV Are Still At Risk for Life-threatening Progressive Multifocal Leukoencephalopathy (PML)

By Liz Highleyman

Progressive multifocal leukoencephalopathy (PML), a potentially severe brain infection caused by polyomavirus JC (JC virus), is an opportunistic infection (OI) sometimes seen in people with suppressed immune function, including those with advanced HIV disease and low CD4 cell counts.

Effective combination antiretroviral therapy (HAART) has dramatically lowered the overall incidence of OIs, but PML remains a risk for HIV positive individuals, according to a Spanish study reported in the September 1, 2008 Journal of Acquired Immune Deficiency Syndromes.

The investigators analyzed the incidence of PML in HIV positive patients, survival, and the characteristics of PML-associated immune reconstitution inflammatory syndrome (IRIS). IRIS refers to a flare-up of symptoms when the CD4 cell count begins to recover with antiretroviral treatment.

This multicenter observational cohort study included all HIV-1-infected patients newly diagnosed with PML at 7 hospitals in Barcelona between 2002 and 2006. These patients were almost all men, had a mean age of about 40 years, and had advanced immune suppression with a mean CD4 count of 90 cells/mm3. Nine patients only learned they had HIV when they were diagnosed with PML; of the remainder, less than half were on antiretroviral therapy.

The authors calculated the annual incidence of PML and estimated survival using the Kaplan-Meier method. IRIS was defined as new onset or rapid worsening of PML shortly after initiation of HAART, together with a decline in HIV viral load and rising CD4 count.

Results

• 61 new cases of PML were diagnosed during the study period.

• The mean survival time after diagnosis was 15 months (95% confidence interval 11 to 19 months).

• The Kaplan-Meier estimates of the probability of survival were:

• 47.7% at 6 months;
• 38.6% at 12 months;
• 35.1% at 24 months;
• 25.1% at 36 months.

• PML-associated IRIS was diagnosed in 14 cases (23%).

• Mortality was similar in patients with and without IRIS.

"PML continues to be one of the deadliest opportunistic infections in acquired immunodeficiency syndrome patients," the study authors concluded. "The development of PML-associated IRIS has no influence on prognosis."

This study indicated that even in the HAART era, PML remains a potentially life-threatening infection. In fact, a few patients developed PML despite having a CD4 count above 200 cells/mm3 and being on antiretroviral therapy with an undetectable HIV viral load.

Unfortunately, there are still no effective treatments for the disease. Another recently published study found that the antiviral drug cidofovir (Vistide), often used to treat cytomegalovirus (CMV) retinitis, failed to reduce mortality or disability due to PML.

9/12/08

Reference
V Falco, M Olmo, SV del Saz, and others. Influence of HAART on the clinical course of HIV-1-infected patients with progressive multifocal leukoencephalopathy: results of an observational multicenter study. Journal of Acquired Immune Deficiency Syndromes 49(1): 26-31, September 1, 2008.
(Abstract).