Middle-aged HIV-positive people have increased risk of 'silent' cerebral vascular disease linked to more severe health problems

Prevalence of silent cerebral small-vessel disease (CSVD) – an important precursor to more serious neurocognitive conditions – is significantly higher among middle-aged HIV-positive people compared to controls in the general population, according to French research published in Clinical Infectious Diseases

After controlling for age, blood pressure and other traditional risk factors, the investigators found that HIV was associated with a doubling in the risk of silent CSVD. HIV-positive people aged between 50 and 54 years had an especially elevated risk of the condition compared to their HIV-negative peers.

“Our study results revealed a high CSVD prevalence among middle-aged PLWHIVs [people living with HIV], despite cART [combination antiretroviral therapy]-sustained immunovirological control,” comment the authors. “We confirmed classical risk factors, e.g. hypertension and advancing age, and identified a specific HIV-associated factor, the nadir CD4-cell count.”



Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.


When blood pressure (the force of blood pushing against the arteries) is consistently too high. Raises the risk of heart disease, stroke, kidney failure, cognitive impairment, sight problems and erectile dysfunction.

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 


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. 


Describes a general decline in physical health and a loss of reserves, most often seen in older people. Frailty leads to a person being less robust and less able to bounce back after an adverse event. A person with frailty may move more slowly, have lost some of their physical strength, have less energy and be less mentally agile. 

CSVD covers a range of abnormalities affecting blood vessels in the brain. In the general population, it is a major cause of cognitive impairment, frailty, altered gait, and is the second most important cause of dementia in the elderly.

Age and hypertension are known risk factors, but its association with HIV is unclear.

Investigators in France therefore designed a cross-sectional study involving middle-aged HIV-positive people, all of whom were doing well on antiretroviral therapy, and matched HIV-negative controls.

The aim was to compare the prevalence of CSVD and severe CSVD according to HIV infection status. MRI scanning – the acknowledged gold standard – was used to diagnose CSVD.

All the HIV-positive people were aged 50 years or older, were taking long-term antiretroviral therapy and had sustained virological suppression. Exclusion criteria included hepatitis C virus co-infection, drug or alcohol abuse and diagnosed neurological disease.

The final study population consisted of 456 people with HIV and 156 controls. Recruitment took place between 2013 and 2016.

People with HIV were younger than the controls (median age 56 vs 58 years, p = 0.001) and were also more likely to be male (85 vs 77%, p = 0.03).

Approximately two-thirds of the HIV-positive sample had been diagnosed before the introduction of effective antiretroviral treatment in 1996. Median nadir and current CD4 cell counts were 196 and 665 cells/mm3, respectively.

CSVD was detected in 52% of people with HIV compared to 36% of the controls. Severe CSVD was present in a fifth of the HIV-positive sample and 14% of HIV-negative people.

After adjustment for age, sex, alcohol use, blood pressure, lipids and history of cardiovascular disease, the investigators found that CSVD was significantly more frequent in people with HIV than controls (aOR = 2.3; 95% CI, 1.5-3.6); however, there was no association between HIV and the risk of severe CSVD.

Overall, the risk of CSVD increased with age.

Despite this, younger HIV-positive participants (50 to 54 years) had a five-fold increase in the risk of CSVD compared to age-matched controls; the risk was three-fold higher for HIV-positive individuals aged between 54 and 60.

Risk factors for CSVD in people with HIV included a nadir CD4 cell count below 200 cells/mm3 (aOR = 1.5; 95% CI, 1.0-2.3).

“Recent study results showing links between CSVD and cognitive and gait impairments, frailty and stroke in the general population and PLHIVs should prompt medical providers to search for CSVD in PLHIVs, using a brief MRI,” conclude the authors, who recommend that screening should be especially targeted at the over-60s.


Moulignier A et al. Silent cerebral small-vessel disease is twice as prevalent in middle-aged well-controlled cART-treated HIV-infected individuals than HIV-uninfected individuals. Clin Infect Dis, online edition, 2017.