Cognitive impairment common in people with HIV despite antiretroviral therapy

Almost 40% of HIV-positive individuals have neurocognitive impairment five months after starting potent anti-HIV therapy, US researchers have found. Their study, published in the September edition of AIDS also revealed that 21% of patients who were not cognitively impaired at this point developed the condition despite continuing to take anti-HIV treatment.

There has been a dramatic and sustained decline in illness and death in HIV-positive individuals since potent anti-HIV therapy became available in 1996. Antiretroviral drugs can reduce viral load in both blood and cerebrospinal fluid and this has lead to a fall in the incidence of HIV-associated neurological disease.

Nevertheless, studies have suggested that as many as a fifth of HIV-infected patients may have cognitive dysfunction and the extent to which antiretroviral therapy leads to a reduction in the prevalence and incidence of HIV-related cognitive impairment is currently disputed. One recent study suggested that antiretroviral therapy improved cognitive function in people with advanced HIV infection.

Cognitive dysfunction becomes apparent in the form of memory loss, confusion, inability to concentrate and changes in personality, including mood swings, depression and anxiety. It can be difficult to diagnose where other conditions co-exist, such as alcoholism, substance abuse or psychiatric problems including depression.

Investigators from the US therefore conducted an analysis of 1,160 HIV-positive patients enrolled in 14 different randomised controlled trials testing the safety and efficacy of anti-HIV drugs to see which factors were associated with both prevalent and incident neurocognitive impairment.

All the patients were African-American or Caucasian. Hispanic patients were excluded because of a lack of validated tests to assess cognitive impairment in this patient group.

Tests to assess neurocognitive function were administered 20 weeks after patients started potent anti-HIV therapy and then 48 weeks later. Statistical analysis was then performed to see if the investigators could identify any risk factors for both prevalent neurocognitive dysfunction (i.e. present after 20 weeks of HIV therapy), or incident dysfunction (i.e. emerged during subsequent anti-HIV treatment).

A total of 39% of patients (458 individuals) were assessed as having cogitative impairment at baseline, with 26% of patients (304 individuals) diagnosed as having mild-to-moderate impairment. However, during follow-up, an improvement in neurocognitive function was observed in 44% of patients.

Age at baseline was significantly associated with an increased risk of prevalent neurocognitive impairment, with patients aged over 55 having the highest prevalence of the condition (p = 0.01). The investigators also found that every 50 cell/mm³ decrease in CD4 cell count at baseline significantly increased the risk of sustained impairment (p 3 decrease in lowest ever CD4 cell count was associated with the presence of impairment at baseline (p

Further analysis revealed that of the 615 patients who had normal neurocognitive function at baseline, 128 (21%) developed impairment during follow-up. The investigators were unable to find any factors to predict which patients had the greatest risk of this occurring.

“A significant subset of individuals have measurable cognitive dysfunction even after starting at least 20 weeks of high active antiretroviral therapy [HAART]”, comment the investigators. They believe that this could “impact on everyday functioning or even medication adherence” of these individuals.

However, the investigators emphasise that many patients experienced an improvement in their cognitive functioning during follow up. “This may be related to the favourable effects of HAART on neurological function.”

Nevertheless, approximately a fifth of patients who were unimpaired at baseline exhibited neurocognitive dysfunction at a subsequent visit. The investigators believe that this could be because some anti-HIV drugs have poor penetration into the central nervous system.