No evidence of accelerated brain ageing in HIV positive people on effective ART
Simon Collins, HIV i-Base
A European study reported no evidence of accelerating brain ageing in HIV positive people on ART, based on highly sensitive brain imaging scans and cognitive testing over two years.
Although some differences were reported at baseline for the HIV positive group, the use of ART was significantly associated with preventing further differences in every domain.
The study was run in Amsterdam and London and is notable for including closely matched HIV negative control groups. Results were presented at CROI 2017 in a late-breaker poster by James Cole from Imperial College London on behalf of the COBRA collaboration. 
The results are also important because people were followed over time and the rates of change related to normal ageing were compared between HIV positive and HIV negative people with similar background risks. Neurocognitive changes are one of the leading concerns held by HIV positive people, especially in relation to ageing.
In this study, 134 HIV positive people on ART with undetectable viral load for at least 12 months and a control group of 79 HIV negative people were enrolled at the Amsterdam Medical Centre and Imperial College London. Retainment in the study was good with follow-up results available for 120/134 HIV positive and 76/79 HIV negative participants (at a median of just under two years (1.9 years).
Mean age at baseline was 57 years (SD+/– 7). In the HIV positive group, the mean CD4 count was strong 646 cells/mm3 (+/– 213) and nadir CD4 showed historical HIV damage 185 (+/– 144) cells/mm3, reflecting a common history shared by many older HIV positive people. Although this was a largely male study, with only nine HIV positive women and six HIV negative women, this reflected the gender balance of the ageing HIV positive population in each country.
Neuroimaging was conducted using multiple modalities of magnetic resonance imaging (MRI) for multiple regions at baseline and after two years, with changes adjusted for age, time between scans, intracranial volume and the type of scanner. Similar adjusted analysis were produced for neuropsychological assessments.
The main results showed that there were some differences between the two groups at baseline, with the HIV positive group having slightly smaller grey matter volume (0.65 vs 0.68 L, p=0.02), abnormal white matter microstructure (p<0.01) and poorer cognitive function (in 4/7 functions: attention, processing speed, motor function and global cognitive performance, all p <0.01), compared to the HIV negative group.
Mean changes between baseline and follow-up were not significantly different between groups in any of the MRI modalities, covering multiple brain regions, including rate of grey matter loss and white matter structure. Nor were there any group differences in the six cognitive domains measured by neuropsychological assessments. Changes that occurred were therefore related to ageing (rather than HIV). Cognitive performance also did not reduce over time and there were minor increases in global cognition in both groups (+0.79 vs +0.45 in HIV positive vs HIV negative, respectively) – suggesting that there may have been a learning effect from the repeated tests.
The researchers concluded that their analysis found no evidence of accelerated brain aging in HIV positive people on ART compared to matched HIV negative controls.
An ongoing analysis is looking for risk factors that can explain the slightly lower baseline results, perhaps related to duration of infection, time before starting ART, nadir CD4 count and lifestyle factors. The results will be just as important as the current study.
Simon Collins is a member of the scientific advisory board for the COBRA collaboration.
These results are reassuring and support another benefit to universal ART that is now recommended in treatment guidelines.
Although the potential factors that might explain the differences between the two groups at baseline were not discussed in the study, the lack of a long-term impact on the rate of further change, even in people who have had low CD4 nadir counts is also encouraging.
It is clearly important for similar research to look at whether results are similar for women, as the low numbers in this study mean it is not powered to show any differences.
Cole JH et al for the COBRA collaboration. Longitudinal analysis shows no evidence for accelerated brain ageing in treated HIV. CROI 2017, 13-16 February 2017, Seattle. Late breaker poster abstract 352LB.
http://www.croiconference.org/sessions/longitudinal-analysis-shows-no-evidence-accelerated-brain-ageing-treated-hiv (abstract and poster)