Does duration of HIV infection substitute for age as a risk factor for amyloid deposition?

Abstract

Increasing access to more tolerable ARV treatments has vastly extended the expected lifespan of People with HIV (PWH), with some models predicting that in developed nations approximately two-thirds of PWH will be older than 50 years by 2030. Longer lifespans increase the risk of age-related neuropathologies, such as the deposition of amyloid beta plaques (Aβ42), regarded as an important prognostic marker of Alzheimer’s Disease (AD). Frequently first detected during mid-life, Aβ42 may predate the manifestation of neurocognitive symptoms associated with AD by 1-2 decades. The etiological significance of Aβ42 deposition in PWH is an active area of investigation. There is little clarity thus far in the clinical and research literature on whether the presence of Aβ42 in PWH leads to elevated risk of developing AD in those with and without HIV Associated Neurocognitive Disorders (HAND). Biological measures of neuropathology, such as CSF serum assays and brain tissue staining, have great potential in determining the extent to which Aβ42 deposition patterns in PWH are HAND-specific, and in linking these deposits to clinical outcomes. In this way, they might provide insight into otherwise seemingly paradoxical findings, such as the observation that neither age nor HIV clinical variables (including ARV status and duration of HIV infection) were able to explain the roughly 5 times greater incidence of mild cognitive impairment (MCI) over a period of 14 months in neurocognitively asymptomatic PWH compared to seronegative controls. In the study by Morgello and colleagues in this issue of AIDS, the authors examined hippocampal and frontal cortical tissue samples from a large cohort of 197 PWH and 63 HIV seronegative controls who donated brain tissue to the Manhattan HIV Brain Bank. Using this approach, they were able to quantify the association of HIV status and the presence of amyloid deposits in brain regions that are typically affected in AD. Despite the study being relatively well-powered, they were unable to identify between- 3 group differences in the occurrence of Aβ42 deposits. Rather, within the PWH cohort, duration of HIV infection, and, somewhat paradoxically, undetectable HIV viral load, emerged as significant predictors of the likelihood of detecting Aβ42.