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The EU-funded four-year COBRA project focused on age-related disorders in persons living with HIV. The researchers concluded that the added risk of developing such conditions may have been exaggerated, and that any such added risk stabilises once patients receive effective treatment.
The project was launched in March 2013 to follow up on a clinical impression that had formed in the HIV arena, says project coordinator Peter Reiss of the Academic Medical Center at the University of Amsterdam.
Patients already seemed prone to conditions such as cardiovascular disease and memory loss at a relatively young age, despite the fact that they were receiving effective treatment for the infection, Reiss explains. This observation led clinicians to speculate that the ageing process in people living with HIV might be affected.
“The belief that ageing was accelerated in people with HIV took hold, without much evidence to back it up,” says Reiss.
COBRA aimed to fill this gap. It involved comparing two groups of people meticulously chosen for similarity in all relevant aspects but one: the first group comprised HIV-infected patients receiving treatment for HIV, whereas the second group comprised people without HIV infection.
Similarity with regard to other relevant aspects – such as age, gender, sexual orientation, and ethnicity or lifestyle specificities such as smoking – was crucial, Reiss observes. “This way, we knew that if we did find a difference, we could say that it was indeed likely to be driven by HIV or its treatment, rather than by known risk factors,” he explains.
However…
The two groups were carefully monitored for signs of cognitive decline. Assessments involving neuropsychological testing and brain imaging were carried out and repeated two years later, Reiss explains.
The assessments did indeed reveal signs of decline over the period, but these were observed in both groups, with no suggestion that the progression was more rapid in one group than the other.
However, he adds, at the start of the study, the HIV-infected group on average already demonstrated evidence, by different measures, of being biologically older than their actual age would indicate, compared to the group without HIV.
As the difference did not appear to grow in patients receiving effective treatment, Reiss assumes that it must arise before. Research conducted on mice enabled the COBRA team to study some of the mechanisms at play.
“The discrepancy is probably due to a combination of factors that happened in the person’s past,” Reiss notes. “One of those factors would be that they’ve lived with untreated or ineffectively treated HIV infection for a long time.”
It is therefore important to diagnose HIV infection as early as possible, says Reiss. “And then, to put people on proper treatment quickly, because that improves their prognosis,” he adds. “This ties in with the current guidelines, which our findings support.”
Managing the risk
‘Biologically older’ may mean ‘likelier to develop a condition related to age’. So there may, indeed, be an added risk of developing such non-communicable diseases to patients receiving treatments for HIV.
However, says Reiss, the degree of added risk may have been exaggerated. “My message to patients would be that if they are diagnosed early and go on proper treatment, they probably don’t need to be too concerned about this issue,” he says. “We really have no evidence of accelerated ageing in people whose infection is treated effectively.”
And there is a lot patients can do to manage other contributing factors – there are a number that significantly increase the likelihood of developing these age-related conditions, says Reiss. “A healthy lifestyle is important for everybody, and certainly for people living with HIV,” he concludes.
Ongoing work
EU funding allowed COBRA to do a more in-depth study of people undergoing general assessments of age-related diseases as part of a larger group participating in the ongoing Amsterdam-based AGEhIV cohort study and the UK-based POPPY cohort study, which are run by some of COBRA’s researchers.
COBRA’s researchers maintain regular contact with each other to discuss and carry out additional analyses of the data and bio-samples collected during the project.