Characteristics of toxoplasmosis encephalitis in HAART era examined

Toxoplasmosis encephalitis remains the most common neurological condition in HIV-positive patients in the HAART era, according to an Italian study published in the December 1^st edition of Clinical Infectious Diseases. The investigators found that individuals with severe immune suppression who were not taking prophylaxis against the infection were at greatest risk, and that patients who were diagnosed with toxoplasmosis encephalitis had a high risk of HIV disease progression and death. These risks were, however, significantly reduced by starting HAART.

In the early 1990s toxoplasmosis encephalitis was the most prevalent infection of the central nervous system in HIV-positive individuals. The infection occurred most frequently in individuals with severely suppressed immune systems, but the incidence of the infection started to fall in the mid-1990s due to the use of prophylaxis. Cohort studies suggest that since the introduction of HAART the incidence of toxoplasmosis encephalitis initially fell further before stabilising, and by 1998 1.9% of all HIV-related deaths were attributable to the infection – a fall from 3.5% in the pre-HAART era.

Italian investigators wished to determine the prevalence, clinical characteristics and survival of HIV-positive patients newly diagnosed with toxoplasmosis encephalitis in the advanced HAART era. In particular, they wished to evaluate the relationship between the occurrence of toxoplasmosis encephalitis and previous exposure to antiretroviral therapy and prophylaxis against toxoplasmosis.

Data were obtained from the Italian Investigative NeuroAIDS study. The records of all 805 HIV-positive individuals diagnosed with an abnormality of the central nervous system between 2000 and 2002 were analysed. A total of 205 of these individuals had been diagnosed with toxoplasmosis encephalitis for the first time and were included in the investigators analysis. Toxoplasmosis encephalitis was the commonest neurological condition diagnosed (26%).

In total 66% of patients were male, the median age was 43 years, and 26% of patients had had a previous AIDS-defining illness. The median CD4 cell count at the time of diagnosis with toxoplasmosis encephalitis was 34 cells/mm³ and the median viral load was 100,000 copies/ml.

Antiretroviral therapy had been used by 76 patients (36%) prior to the development of toxoplasmosis encephalitis, and 66 (87%) of these patients had received HAART for a median of 24 months prior to their neurological diagnosis. At the time of diagnosis with toxoplasmosis encephalitis 44 of these patients were still taking HAART.

Of the patients who were taking HAART, at the time of neurological diagnosis 11% had a CD4 cell count above 200 cells/mm³ and 12% had an undetectable viral load.

When the investigators studied the data for the entire study population of 805 patients they found that male sex (p = 0.02), previous exposure to antiretroviral therapy (p = 0.02), the use of prophylaxis against toxoplasmosis encephalitis (p = 0.02), and a higher CD4 cell count at the time of neurological diagnosis decreased the risk of developing toxoplasmosis encephalitis.

Prophylaxis against toxoplasmosis was only being taken by 35 (17%) of the 205 patients diagnosed with the condition. Furthermore, the investigators note that 31 (66%) of the 47 patients taking antiretroviral therapy with a CD4 cell count below 100 cells/mm³ were not taking prophylaxis against toxoplasmosis encephalitis when the condition was diagnosed.

In the six months after diagnosis with toxoplasmosis encephalitis the median exposure to HAART was 150 days. After six months, 76% of patients had experienced an improvement or resolution of their neurological infection. Patients with pervious experience of antiretroviral therapy were significantly less likely to experience an improvement in their neurological condition (OR, 0.25).

After a year of follow-up, a total of 34 (16.1%) patients had died, 25 of whom died in the first six months of their neurological diagnosis. In total 22 deaths were due to toxoplasmosis encephalitis and 24 patients experienced a new AIDS-defining event.

The one year probability of clinical disease progression was 40%. The presence of cogitative symptoms independently increased the risk of HIV disease progression (p = 0.05), and a CD4 cell count above 100 cells/mm³ (p = 0.05), and the receipt of HAART at the time of diagnosis with toxoplasmosis encephalitis diagnosis (p = 0.001) both independently reduced the risk of HIV disease progressing. The only factor independently associated with an increased risk of death was abnormal mental status (p = 0.03), whereas the receipt of HAART within two months of diagnosis with toxoplasmosis encephalitis independently reduced the risk of death (p = 0.001).

“Toxoplasmosis encephalitis remains the most prevalent cause of HIV-associated neurological disorders, even in the late HAART era, with an increased risk observed in antiretroviral-naïve patients”, write the investigators. They conclude, “because toxoplasmosis encephalitis was associated with a high probability of early death, all strategies to avoid toxoplasmosis encephalitis occurrence, such as not delaying HAART until there is a high risk of clinical progression and maintaining prophylaxis in immunosuppressed patients for who HAART has failed, should be considered.”