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.
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
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
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