Risk score can identify which HIV-positive people with controlled viral load are at greatest risk of neurocognitive decline

Four factors are associated with neurocognitive decline in people living with HIV with an undetectable viral load, investigators from Canada report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The strongest individual risk factor was impaired kidney function, indicated by eGFR < 50ml/min/1.73 m2. People with all four risk factors had a 95% risk of neurocognitive decline over three years, compared to a 2% risk for people with no risk factors.

“The personalized risk index included four clinical factors that were significant predictors of neurocognitive decline,” comment the authors. “Lower eGFR was the strongest predictor.”

Neurocognitive changes such as memory loss, inability to remember words, loss of verbal fluency, poor concentration and inability to take in new information or make complex decisions are features of ageing, but happen at different speeds for different people. A number of health conditions may have an impact on neurocognitive function.


prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 

cerebrospinal fluid (CSF)

The liquid surrounding the brain and spinal cord.

concentration (of a drug)

The level of a drug in the blood or other body fluid or tissue.


A substance which forms the structure of most cells and enzymes.


Involving the brain.

There is a body of research suggesting that people with HIV remain at increased risk of neurocognitive decline, even when they are taking effective antiretroviral therapy and have an undetectable viral load. The risk factors for decline in these people are uncertain. Identification of such risk factors could assist the development of targeted interventions to prevent avoidable declines.

Investigators from McGill University, Canada, therefore designed a prospective study involving 191 HIV-positive adults, all with a controlled viral load. Their aim was to determine the baseline socio-demographic, clinical, biological and lifestyle factors associated with neurocognitive decline.

Individuals were monitored for three years. At six-monthly intervals, they underwent a battery of 15 tests to assess neurocognitive function. Individuals who deteriorated by at least 0.5 SD on at least one assessment were defined as having neurocognitive decline.

On entry to the study, the participants had a median age of 45 years, 74% were male and 52% were non-Caucasians. Participants had spent a median of 12 years in education, and had been living with diagnosed HIV infection for a median of ten years. Average current CD4 cell count was 514 cells/mm3. Almost all (94%) were currently taking HIV therapy.

Over three years, 23 people (12%) showed evidence of decline in at least one neurocognitive assessment.

After controlling for potential confounders, four baseline factors had a significant association with neurocognitive decline:

  • eGFR < 50 ml/min/1.73 m2 (OR = 18.14; 95% CI, 1.53-254.53).
  • Diagnosed HIV infection for 15 or more years (OR = 11.14; 95% CI, 1.61-88.08).
  • Education for 12 years or less (OR = 5.45; 95% CI, 1.44-24.09).
  • Cerebrospinal fluid (CSF) protein above 45 mg/dl (OR = 4.55; 95% CI, 1.36-15.74).

The authors suggest that impaired eGFR could be indicative of vascular disease in both the kidney and the brain. “Lower eGFR is a known independent predictor of atherosclerotic vascular disease,” they note. “In non-HIV individuals, lower eGFR has been independently associated with lower cerebral blood flow, cognitive decline and increases the risk of recurrent stroke and small brain infarctions, both possible risk factors for cognitive decline.”

However, they emphasise that more research is needed to understand the relationship between declining kidney function and neurocognitive changes.

People with longer duration of HIV infection could, the investigators suggest, have had a considerable amount of time without effective HIV treatment.

The background risk of decline over three years was 2% for individuals with none of these four risk factors. Having only impaired eGFR increased the risk to 21%. Having all four risk factors was associated with a 95% increase in risk.

“Providing patients with their individualized risk of cognitive decline may increase their motivation for behavioral changes and adherence to treatment,” conclude the authors. “The case will become more compelling as the findings are replicated in other samples, and the link between the neurocognitive outcome we studied and real life function is established.”

Lifestyle factors such as diet, exercise, alcohol intake, smoking and weight may be amenable to change and may result in improved cognitive function, but more research is needed on this topic in people living with HIV.

Further information

See NAM's factsheet on cognitive impairment and HIV for further information on this subject.


Yuen T et al. Personalized risk index for neurocognitive decline among peole with well-controlled HIV infection. J Acquir Immune Defic Syndr. Online edition. DOI: 10.1097/QAI.0000000000001466 (2017).