Cognitive function improves through the first year of HIV therapy

Michael Carter
Published: 29 March 2012

Cognitive function continues to improve up to one year after starting antiretroviral therapy, according to the results of a small international study published in HIV Medicine.

The investigators monitored changes in cognitive function six and twelve months after patients started therapy. Significant overall improvements were observed at both time points.

Changes in cognitive function varied according to treatment regimen and improvements were less pronounced in patients taking a regimen based on efavirenz (Sustiva, also in Atripla) than those seen in people taking alternative regimens.

“Overall, and of clinical relevance, we observed improvements in neuro-cognitive function in neuro-asymptomatic HIV-infected subjects commencing antiretroviral therapy for the first time,” write the authors. “The majority of improvements were present within 24 weeks of commencing therapy and continued improvements were observed until 48 weeks after starting therapy.”

It is well recognised that starting HIV treatment can lead to improvements in neuro-cognitive function. However, few studies have explored the timing or dynamics of cognitive changes in people starting antiretroviral treatment.

Investigators from the ALTAIR study therefore designed a sub-study involving 28 patients. All these people were starting HIV therapy for the first time and none had symptomatic cognitive dysfunction.

All the patients received FTC/tenofovir (Truvada). They were randomly allocated a third drug: efavirenz; ritonavir-boosted atazanavir (Reyataz); or AZT + abacavir (Ziagen).

Neuro-cognitive function was assessed at baseline using a battery of computerised tests. These measured detection, identification, speed, working memory and executive function. The tests were repeated 24 and again 48 weeks after treatment was started.

None of the patients were taking antidepressants or anti-psychotic therapy, and people with drug or alcohol problems, as well as those with hepatitis C-co-infection, were excluded from participation.

Median CD4 cell count increased from 218 cells/mm3 at baseline to 342 cells/mm3 at week 48, at which point all but one patient had an undetectable viral load.

Improvements in neuro-cognitive function were observed at week 24 and these continued through to week 48. The overall increases in neuro-cognitive scores were 0.16 at week 24 and 0.18 at week 48. Improvements in speed scores were also observed at both time points (week 24: - 0.09; week 48: - 0.14, a negative score indicating increased speed and improved response). 

Overall, accuracy scores improved by week 24 but were unchanged at week 48 (0.24, 0.24). Executive functioning also improved, but this was not apparent until week 48.

Neuro-cognitive performance varied between the study arms. Most notably, speed scores deteriorated slightly for patients in the efavirenz arm while improving for patients taking the other study medications. By week 48, the difference between the efavirenz and the AZT/abacavir arms was significant (p = 0.04).

The investigators suggest this finding could be due to “a specific effect of efavirenz…acute neuropsychiatric disorders are well described with efavirenz use and may persist with extended therapy.”

Significant improvements in executive function were not seen until week 48, and then only in the AZT/abacavir-treated patients (p = 0.02).

“Improvements in neuro-cognitive function in individuals commencing combination antiretroviral therapy for the first time may be related to control of HIV viraemia and/or recovery of cerebral synaptodendritic injury,” comment the authors.

They believe their findings “may assist in the design and development of future treatment and research programmes assessing changes in cerebral function over time in HIV infected subjects”.

Reference

Winston A et al. Dynamics of cognitive change in HIV-infected individuals commencing three different initial antiretroviral regimens: a randomized, controlled study. HIV Med 13: 245-251, 2012.