Dr Michael Seah
Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.
CNS Treatment Strategies - risks and benefits
I tried something a little different this afternoon. The conference venue set up a simulcast of all concurrent sessions in a theatre-like venue with six screens displaying the slides from each session. Audio was provided by personal channel-selected headphones, much like the system used in some gymnasiums broadcasting TV audio to users. It was a great way to flick between sessions rather than having to run between rooms. Despite this great technology, the human limitation still applies, and you can only pay attention to one presentation at a time!
The themed discussion afternoon consisted of 4 or 5 short presentations, following by robust discussion with the audience. The session on CNS treatment strategies addressed the issue about HIV and the CNS, in particular the issue of the potential for neurocognitive deficits to persist despite apparent complete viral suppression on ART. This effect is likely due to reservoir seeding to a sequestered site, resulting in ongoing immunogenitic and inflammatory effects of HIV, as discussed at other points at the conference.
The CNS is an early target for HIV. HIV-associated Neurocognitive Disorder (HAND) encompasses the spectrum of disorders related to HIV infection and AIDS, and includes disorders of varying severities. What is known is that early identification and treatment improves HAND, and ART improves established HAND.
A study into whether delays in ART initiation would impair neurocognitive function compared initiation immediately after infection with a 24 week delay. Interestingly, early initiation led to a greater improvement in neurocognitive function over time. The observation has important implications to clinical practice and in discussions with patients about when to start treatment. Early ART initiation may prove to be an important treatment strategy to decrease the severity of HAND or lead to better improvement in HAND. [TD-380]
The next presentation looked at the cognitive trajectories over 4 years of HIV positive women with optimal viral suppression. There was a lower baseline cognitive function in several neurocognitive domains (attention, learning, memory and global functioning) in the HIV infected group compared with demongraphically similar uninfected women. The difference observered was at least one standard deviation worse across these domains and persisted over time. In the domain of motor skills, where there was no difference at baseline, a decline was observed over the 4 year period.
In comparing women who were virally suppressed with those that were not, in some domains (eg. global function) there was no difference in the measured decline over time. Interestingly, in some domains (eg. attention and fluency) virally suppressed women actually performed worse than non-virally suppressed women.
The difference at baseline may be attributed to co-morbidities such a susbtance use, trauma and psychological risk factors. These, combined with a low cognitive reserve, are hypothesised to be contributing to accelerated CNS ageing.
The vulnerabilities in various neuropsychological domains provides a framework for further study into the pathophysiology of the CNS damage observed. Clinically it is important to understand how co-morbidities in HIV infected individuals may be contributing to the HIV specific effects. [TD-350]
CCR5 blockade using Maraviroc intensification has been shown to improve cognitive performance in HIV infected adults on ART. CCR5 binds multiple chemokines and is a co-receptor for HIV.
Cenicriviroc (CVC) is an new oral dual CCR2 and CCR5 antagonist. CCR2 is a chemokine receptor for the monocyte chemoattractant MCP-1. Monocytes have been implicated with contributing to HIV-associated Neurocognitive Impairment (HIV NCI). In ART naive HIV infected adults, CVC has been shown to decrease viraemia and soluble CD14 levels (CD14 is a marker for monocyte activation). Additionally, in animal models CVC has been shown to have anti-inflammatory and anti-fibrotic activity.
The pilot study hypothesised that CVC will improve cognitive function in HIV NCI by reducing monocyte activation. The sample cohort was older (average age 55), ART experienced (average 16 years on ART) and had low cognitive performance at baseline. Depression was an exclusion criterion. Neuropsychological testing was conducted at entry and at 24 weeks, along with plasma markers of monocyte activation (neopterin, soluble CD14 and sCD163).
The study observed that CVC intensification improved global cognitive performance, along with specific improvements in the neurospsychological subdomains of working memory and attention. There was a positive trend seen in the domains of psychomotor speed and visuospatial. Monocyte activation was significantly decreased with all three markers measured, with a trend seen between neopterin and working memory scores.
Although only a small study (17 participants) the results are certainly promising. Even in virally suppressed, ART experienced individuals, the measured improvements in cognitive function at 24 weeks suggests that HIV NCI may be treatable. Additionally, neopterin may be a predictor of improvement in working memory. A larger randomised control trial in HIV infected people with cognitive abnormalities is required to explore these effects further. [TD-381]