Depression adversely affects cognitive function of people with HIV in both the short- and longer-term

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Sustained depression is associated with long-term declines in cognitive function among people living with HIV, investigators from the United States report in the Journal of Acquired Immune Deficiency Syndromes. Executive functioning, recall and verbal fluency were all adversely affected by long-term depression. The study also showed that acute depression also had an impact on key aspects of cognitive function, including motor skills and speed of thought.

“Higher depression burden was associated with faster declines in global neurocognitive functioning from baseline to last visit,” comment the researchers. “We also found an association between acute, visit-to-visit depressive symptom severity and global neurocognitive performance within persons, such that participants had lower global cognitive scaled scores on visits when they reported more severe depressive symptoms.”

Over a third of people living with HIV experience depression – five times the rate seen in the general population. In the context of HIV, depression not only has a major impact on quality of life but also is associated with poorer overall health outcomes.  



A mental health problem causing long-lasting low mood that interferes with everyday life.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

drug interaction

A risky combination of drugs, when drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

longitudinal study

A study in which information is collected on people over several weeks, months or years. People may be followed forward in time (a prospective study), or information may be collected on past events (a retrospective study).

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

However, research examining the impact of depression on cognitive function in people with HIV has yielded mixed results.

Given this uncertainty a team of investigators led by Emily Paolillo of the University of California San Diego designed a longitudinal study (i.e. repeated observations over an extended period of time) to determine the relationship between depressive symptoms and cognitive function in people with HIV. The study examined the impact of depression severity on both long- and short-term outcomes.

Cognitive function was monitored using a range of tests assessing verbal fluency, executive functioning, speed of information processing, learning, recall, working memory and speeded fine motor skills (dexterity, co-ordination).

The study population consisted of 448 individuals. The cohort was predominantly male, ethnically diverse and had a mean age of 44.

At baseline, 67% had a low burden of depression, 15% a medium burden and 17% a high burden of depression. Participants had a mean of five follow-up visits with approximately a year between each visit.

Individuals with a high burden of depression had steeper declines in cognitive function during follow-up compared to the low depression group (p = 0.001). Decline in cognitive function was also more pronounced in the medium depression group compared to the low depression group, but this difference fell just short of the test used by the researchers to assess statistical significance (p = 0.057).

The cognitive decline observed in people with the most severe burden of depression was driven by declines in executive function (p = 0.02), delayed recall (p = 0.023) and verbal fluency (p = 0.045). The medium depression group also had declines in executive function (p = 0.039) and verbal fluency (p = 0.001).

"Executive functioning, recall and verbal fluency were all adversely affected by long-term depression."

The researchers explore possible mechanisms for the relationship between depression and cognitive decline.

Firstly, there is a well-established connection between depression and poorer adherence to HIV treatment, which could allow viral load to rebound, increasing the risk of HIV-related neurocognitive impairment. Paolillo and colleagues also point to research that has shown that sustained depression and stress can cause chronic neuroinflammation, which in turn can lead to neuronal damage.

Reduced social interaction is also posited by Paolillo and her fellow investigators as another possible reason for their findings. Depression is associated with reduced engagement in physically, socially and intellectually stimulating activities, all of which  are known to be protective against cognitive decline in older people.

There was also evidence that more severe depressive symptoms had an impact on cognitive function. Analysis of individual results showed that cognition was poorer on days when individuals reported symptoms of mild (p = 0.042) and moderate-to-severe (p = 0.026) depression. This was most evident in worsened motor skills and processing speeds.

“Our findings demonstrate both acute effects of depressive symptom severity on neurocognitive performance…and chronic effects on cumulative depression severity and long-term neurocognitive decline,” conclude the authors. “The declining neurocognitive functioning observed among people with HIV with the highest cumulative burden of depression may also be reciprocally related to the poorer healthcare engagement and HIV-related health outcomes in this group.”

Paolillo and colleagues add that more research is needed to examine how treatment for depression affects cognitive, mental and physical health.


Paolillo EW et al. Cumulative burden of depression and neurocognitive decline among persons with HIV: a longitudinal study. Journal of Acquired Immune Deficiency Syndromes, online ahead of print, March 2020.

doi: 10.1097/QAI.0000000000002346