People who experience episodes of major depressive
disorder (MDD) are significantly more likely to have episodes of detectable HIV in their cerebrospinal
fluid (CSF), according to an analysis of the large CHARTER study presented as a
late-breaker poster at the 53rd Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC) last week in Denver.
antiretroviral therapy (ART) has dramatically lowered rates of AIDS-related dementia,
many people living with HIV still experience more subtle cognitive impairment
or neuropsychiatric problems.
Edward Hammond from Johns Hopkins University in
Baltimore and colleagues conducted a study to determine if major depressive
disorder is associated with HIV escaping or shedding into CSF, the fluid that
surrounds the central nervous system comprised of the brain and spinal cord.
Past research has linked MDD to poor virological
control and faster disease progression among people with HIV, the researchers
noted as background. While major depression is known to be associated with
persistent detectable HIV RNA in CSF, it is not clear whether the same
association holds for sporadic detectable CSF viral load among people with
undetectable blood plasma viral load while on ART.
Certain antiretroviral drugs are able to cross the
blood-brain barrier to fight HIV in the central nervous system. Some experts
favour specifically including such drugs in antiretroviral regimens, but others
think that all guideline-recommended modern combinations that fully suppress
HIV in the blood are adequate to control virus in the brain.
The researchers looked at data from participants
in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort, a
prospective cohort of people with HIV at six US centres designed to evaluate
neurocognitive and neuropsychiatric outcomes of HIV treatment.
The investigators used logistic regression and
discrete-time survival models to examine associations between MDD diagnosis
(according to the 1994 edition of the Diagnostic
and Statistical Manual of Mental Disorders, or DSM-IV) and HIV "escape"
into CSF, both at study entry and over time.
CSF viral escape was defined as detectable HIV RNA
(>50 copies/ml) in the presence of undetectable blood viral load (<50
copies/ml), or CSF viral levels at least 1 log greater than blood levels.
The main analysis included 803 participants. Most
(81%) were men, 41% were white and 46% were black. The average age was 44 years
and they'd had HIV for about 11 years. The median current CD4 cell count at
study entry was 445 cells/mm3, but the nadir (lowest-ever) level
was 149 cells/mm3. Half had a prior history of major depression
At study entry, 18% of participants overall were found
to have detectable HIV in their CSF despite undetectable blood viral load.
People with major depression were nearly twice as likely to have CSF viral
escape than non-depressed participants: 26 vs 16% (p = 0.016; adjusted odds
A subset of 212 participants who did not have detectable
CSF viral load at the start of the study underwent at least three more spinal
taps during follow-up to see if they experienced new-onset viral escape into their
Over 18 months of follow-up (2736 total person-months),
cumulative incidence of CSF viral escape was again significantly higher among
people with MDD compared to non-depressed participants (p<0.05).
New-onset CSF viral escape was somewhat more common
earlier in the study. At six months, incidence rates were 27 cases per 1000
person-months among people with MDD compared to 16 per 1000 person-months
among non-depressed participants. At 12 months, cumulative incidence rates were
19 vs 12 cases per 1000 person-months, respectively. At 18 months, incidence
rates remained stable at 20 vs 12 cases per 1000 person-months.
After controlling for other factors, the adjusted
hazard ratio for new-onset CSF escape among people with MDD was 3.01, or three
Plasma viral load levels did not differ significantly between
people with MDD and those without at any time point. Having a lifetime history
of major depression was a significant risk factor for later episodes, and
current CD4 count (but not lowest-ever count) approached statistical significance.
"MDD is associated with increased risk for CSF
viral escape," the researchers concluded. "Ongoing CSF viral
replication may occur in more persons than previously estimated. Evaluation and
treatment of depression may improve HIV control."
"Additional research is needed to continue to
improve our understanding of mechanisms that may be responsible for the
relationship between depression and HIV viral replication," they added.