Broad range of risk factors associated with mild cognitive impairment in HIV-positive men on ART

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A broad range of factors are associated with cognitive impairment in middle-aged HIV-positive men, according to Dutch research published in the online edition of AIDS. The observational, cross-sectional, case-controlled study involved antiretroviral-treated participants with sustained viral suppression. Reduced cognitive function was associated with cannabis use, depression, metabolic factors and previous HIV-related immune suppression. 

“Decreased cognitive performance probably results from a multifactorial process,” comment the authors.

Mild cognitive impairment can become evident in the form of changes such as reduced attention span, slower information processing, reduced fluency in the use of language, and a reduced ability to plan and organise everyday life or to solve problems. These changes are considered by specialists to exceed the declines in memory and mental sharpness that usually accompany ageing.


cognitive impairment

Loss of the ability to process, learn, and remember information. Potential causes include alcohol or drug abuse, depression, anxiety, vascular cognitive impairment, Alzheimer’s disease and HIV-associated neurocognitive disorder (HAND). 


Relating to the heart and blood vessels.


In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 


The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.


Relating to the brain or central nervous system.

In some cases mild cognitive impairment may be an early warning sign of Alzheimer's disease and people who develop mild cognitive impairment are at increased risk of going on to develop Alzheimer's disease. However, mild cognitive impairment can have numerous causes, including cardiovascular disease, drug use, medication side effects, vitamin and thyroid deficiency, and depression or anxiety, many of which are treatable.

A high prevalence of mild cognitive impairment has been reported among people with HIV, even when they are doing well on antiretroviral therapy. Rates as high as 59% have been reported in some studies, but it seems that criteria used to diagnose the condition have been oversensitive and that diagnoses have included a large number of false positives.In particular studies may define people as having mild cognitive impairment as a result of having reductions in some, but not all, cognitive functions.

In order to establish a more accurate understanding of the prevalence of mild cognitive impairment among people with HIV in the era of modern antiretroviral era, investigators in Amsterdam have used a form of analysis called multivariate normative comparison (MNC). This technique controls for false positives while still able to capture cases of impairment, by comparing outcomes of all an individual's cognitive function tests to the distribution of average results in the age-matched reference population.

The team of investigators who pioneered this analysis now wanted to gain a clearer understanding of the factors associated with mild cognitive impairment in middle-aged people with HIV who were responding well to antiretrovirals. They hypothesised that a number of factors would be involved with the condition, including drug/alcohol use, mental health problems, metabolic and cardiovascular risk factors and factors related to HIV infection and its treatment.

Individuals enrolled in the AGEhIV study of age-associated illness in people with HIV were recruited to a cognitive substudy between 2011 and 2013. Recruitment criteria included current HIV therapy with viral suppression for at least twelve months. Exclusion criteria included serious neurological disease, ongoing psychiatric disorders, current injecting drug use, daily use of illicit substances (with the exception of cannabis), traumatic brain injury and past/current HIV-related neurological disease.

A total of 103 HIV-positive men were recruited to the study and they were matched with 74 HIV-negative controls. Median age in both groups was 54 years. The HIV-positive men had had an undetectable viral load for a median of eight years. Just over a third (35%) had experienced a previous AIDS-defining illness and average nadir CD4 cell count was approximately 170 cells/mm3, but current average counts were 625 cells/mm3.

The patients and controls were well matched. However, smoking was more prevalent among the HIV-positive participants, who also had lower body mass index and a higher waist-to-hip ratio when compared to HIV-negative individuals.

A wide battery of tests was used to assess the neurocognitive function of both the HIV-positive men and controls. Their results showed that 17% of the HIV-positive men and 5% of the controls had mild impairment.

Factors associated with impairment in the HIV-positive group included cannabis use, a history of cardiovascular disease (borderline significance), impaired renal function (borderline significance), above normal waist-to-hip ratio, the presence of depressive symptoms and a low nadir CD4 count. In further analysis, cannabis use (p < 0.001), history of cardiovascular disease (p = 0.014), impaired renal function (p = 0.017) and diabetes (p = 0.097 - borderline) remained independently associated with cognitive impairment.

The authors note that many of these associations have been identified in previous studies and are biologically plausible. They acknowledge because the study was cross-sectional, it was “merely able to demonstrate associations rather than causality.” The study population was male, Caucasian and had a very low prevalence of viral hepatitis co-infection, possibly meaning that the findings may not apply to other populations.

“Our results indicate that reduced cognitive performance in HIV-1 infected men with sustained suppressed viraemia on cART [combination antiretroviral therapy] is likely to be a multifactorial process, in which not only HIV-1 associated factors such as having experienced more severe immune deficiency, but also cardiovascular/metabolic factors, cannabis use, and depressive symptoms are key contributors,” conclude the authors. “These are likely to gain increased importance as the population of people living with HIV continues to age.”


Schouten J et al. Determinants of reduced cognitive performance in HIV-1 infected middle-aged men on combination antiretroviral therapy. AIDS, online edition. DOI: 10.1097/QAD.00000000000001017 (2016).