Neurocognitive impairment results in poorer adherence to HIV therapy

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Neurocognitive impairment and problems with memory are associated with poorer adherence to antiretroviral therapy, investigators from the United States report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The study also showed that better adherence was associated with greater reductions in viral load in cerebrospinal fluid.

The investigators propose that “NP [neuropsychological] impairment and non-adherence may be linked by a vicious cycle in which initial non-adherence results in ongoing HIV replication, which exacerbates NP impairment and results in worse adherence.” They believe their results have implications for the care of people with HIV, and that people with neurocognitive impairment, especially memory problems, would benefit from adherence support.

Thanks to improvements in treatment and care, the life expectancy of many people with HIV is now normal. Current antiretroviral treatment regimens are potent, safe and are often taken just once daily. Nevertheless, adherence remains central to the success of HIV treatment and a significant proportion of people living with HIV find it difficult to take their medication as prescribed and thus do not benefit fully from their treatment.


cerebrospinal fluid (CSF)

The liquid surrounding the brain and spinal cord.

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. 


Confounding exists if the true association between one factor (Factor A) and an outcome is obscured because there is a second factor (Factor B) which is associated with both Factor A and the outcome. Confounding is often a problem in observational studies when the characteristics of people in one group differ from the characteristics of people in another group. When confounding factors are known they can be measured and controlled for (see ‘multivariable analysis’), but some confounding factors are likely to be unknown or unmeasured. This can lead to biased results. Confounding is not usually a problem in randomised controlled trials. 


The fluid portion of the blood.

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

Mild neurocognitive impairment is common in people with HIV. Its impact on daily life is uncertain, but it is possible that problems with memory result in some people forgetting to take their treatment. Indeed, forgetful is the reason most commonly cited by people who miss doses.

Investigators from the CNS Anti-Retroviral Therapy Effects Research (CHARTER) study therefore designed a prospective study involving 80 adults with HIV to see if there was a relationship between neurocognitive function and antiretroviral adherence.

Neurocognitive, psychiatric and substance abuse status were assessed at baseline and again after six months. Adherence was measured using pharmacy refill records, with attention focused on the anti-HIV drug with the greatest brain penetration. The investigators then undertook a series of analyses to see if neurocognitive function was associated with adherence and viral load in blood and cerebrospinal fluid.

“We hypothesized that NP deficits and mood and substance use would predict ART adherence, and that adherence would be associated with virologic responses in plasma and cerebrospinal fluid,” write the authors.

Recruitment to the study took place between 2003 and 2007. The majority of participants were African-American (56%) and male (79%). Median CD4 cell count was 383 cells/mm3 and patients had been taking their antiretroviral treatment regimen for a median of eight months before baseline assessment.

Almost half (49%) the patients had a lifetime history of depression and substance abuse or dependence was highly prevalent (83%). The mean level of adherence to the anti-HIV drug with the greatest brain penetration was 86%.

Standard assessments of cognitive function showed that half the patients were impaired.

Factors associated with better treatment adherence included male sex, higher social economic status, longer duration of HIV therapy, less substance abuse and better cognitive function.

After controlling for confounding factors, the investigators found that male sex (p = 0.017), longer duration of HIV infection (p = 0.002) and better overall neuropsychological scores (p = 0.033) all had a relationship with better adherence. 

Closer analysis showed that low “working” memory scores were associated with poorer treatment adherence (p = 0.026).

“HIV-infected participants with greater overall NP deficits and specific deficits in working memory have lower ART adherence,” comment the researchers.

Only twelve patients had detectable HIV in cerebrospinal fluid at baseline. The investigators found that better adherence was associated with greater declines in viral load in cerebrospinal fluid among these patients. “Better adherence…was associated with decreasing levels of cerebrospinal fluid HIV RNA over a six month time period.”

They conclude, “careful assessment of working memory and cognition prior to ART initiation and in patients with suboptimal virologic responses to ART may help identity persons in need of adherence support.”


Andrade ASA et al. Relationships among neurocognitive status, medication adherence measured by pharmacy refill records, and virologic suppression in HIV-infected patients. J Acquir Immune Defic Syndr. Online edition, DOI: 10.1097/QAI.0b013e31827cd678, 2012.