Cidofovir of no benefit for HIV-related PML

Treatment with the antiviral drug cidofovir has no benefits for HIV-positive patients with PML (progressive multifocal leukoencephalopathy), researchers conclude in an article published in the September 12^th edition of AIDS. The investigators compared treatment outcomes in HIV-positive patients with PML who were treated with antiretroviral therapy plus cidofovir and patients with the infection who received antiretroviral therapy by itself. They found that mortality and disability were comparable in the two treatment groups.

Cidofovir treatment can damage the eyes and kidneys, and given its apparent lack of benefit for patients with PML the investigators recommend “cidofovir should be abandoned in patients with AIDS-related PML.”

PML is a disease of the central nervous system caused by the JC virus. It affects individuals with very weak immune systems. In patients with HIV, it usually causes progressive neurological symptoms, often resulting in death within four to six months. The prognosis of HIV-positive patients with PML has improved since effective HIV treatment became available, and there is some evidence that antiretroviral therapy restores PML-specific immune responses. Nevertheless, approximately 50% of HIV-positive patients with PML still die or have severe disability.

The only treatment currently recommended for PML is antiretroviral therapy, but laboratory tests, as well as some small studies, have suggested that patients treated with antiretroviral therapy and cidofovir have a better chance of survival than individuals treated with HIV therapy alone. But the number of patients in these studies was small, and they have been contradicted by other research.

Therefore an international team of investigators looked at the results of six studies conducted between 1996 and 2004 where HIV-positive patients with PML received treatment for PML with antiretroviral therapy plus cidofovir or antiretroviral therapy alone. The researchers compared rates of death and disability between these two groups of patients.

A total of 370 patients were included in the investigators’ analysis. All the patients received antiretroviral therapy and 50% also received treatment with cidofovir. Treatment with cidofovir was administered eight weeks after the diagnosis of PML in 75% of patients and the median number of cidofovir treatment cycles was five.

A total of 189 (51%) patients died and in 167 (89%) of these individuals, PML was considered to be the cause of death.

The investigators calculated that the patients treated with cidofovir had a slightly lower probability of survival after one year (44%) compared to patients who only received antiretroviral therapy (55%), but this difference was not statistically significant.

The only factors associated with an improved chance of survival were a higher CD4 cell count (p Karnofsky score (an assessment of an individual’s health and well-being)(p

Of the patients who were alive after twelve months, 39% were assessed as having moderate to severe disability. The investigators’ univariate statistical analysis showed that treatment with cidofovir (p = 0.016) and JC viral load in cerebrospinal fluid (p = 0.01) were significantly associated with a higher risk of moderate to severe disability and that a higher CD4 cell count (p = 0.027) and a higher Karnofsky score (p

Most of the studies included in this analysis had an observational design, but despite this limitation the investigators write “the overall results point against a major effectiveness of cidofovir in the treatment of AIDS-related PML.” They conclude “new agents and treatment strategies are urgently needed for the treatment of this uncommon but frightening opportunistic infection.”