CROI: Persistent brain impairment despite HIV treatment linked to severity of prior dementia

Christopher Gadd
Published: 24 February 2006

Almost two thirds of patients with HIV dementia do not show improvements in their condition despite three years of HIV treatment, according to an Italian study presented earlier this month at the Thirteen Conference on Retroviruses and Opportunistic Infections in Denver.

The study revealed that these patients were more likely to have severe brain impairment before treatment and to show a smaller improvement in the first few months of treatment than those whose dementia improved.

This leads the investigators to suggest that anti-HIV treatment should be started as soon as brain impairment is diagnosed, to avoid it becoming irreversible.

Antiretroviral drug combinations are known to improve the impairment in thought, movement and personality seen in some patients with HIV infection. However, previous studies have found that 'neurocognitive impairment' does not completely resolve in over half of patients treated with anti-HIV drugs.

To investigate factors associated with persistent neurocognitive impairment, investigators from Rome carried out neurological tests on 166 patients with HIV-related neurocognitive impairment before they started antiretroviral therapy and regularly for up to four years. Sixty-eight (59%) of the patients had never taken anti-HIV drugs before.

Overall, the patients’ condition improved significantly from six months after starting HIV treatment (p < 0.05). The biggest improvements were seen in mental flexibility and the control of fine movements.

However, only 35 (30%) of the patients had reversible neurocognitive impairment, with the remainder still having significant impairment after a mean follow-up of 32 months.

“Although highly active antiretroviral therapy (HAART) was associated with improvements in cognitive functions, the impairment persisted in nearly two of three cases, despite three years of HAART,” the investigators conclude.

Using multivariable analysis, the investigators found that the likelihood of a patient having persistent impairment were associated only with the severity of impairment at the start of the study (odds ratio [OR] = 5.5; p = 0.001) and the degree of improvement in the first six months of HIV treatment (OR = 6.9; p < 0.001).

The risk of a patient having persistent impairment was unaffected by their use of brain-penetrating HIV drugs in this study. There were also no significant differences between groups in age, stage of HIV disease, HIV risk category, CD4 cell count, viral load, response to anti-HIV treatment, education level or gender.

“Less severe impairment and prompt improvement in cognitive performance were independently associated with reversible neurocognitive impairment,” they explain. “Our data indicate that HAART should be initiated as soon as neurocognitive impairment is diagnosed to avoid a potentially irreversible neurological damage.

“Additional treatment strategies are needed in patients with persistent neurocognitive impairment,” they add.

Reference

Tozzi V et al. Factors associated with persistent neurocognitive impairment despite long-term HAART in patients with HIV dementia. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 354, 2006.