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ICAAC 2013: Depression Linked to Detectable HIV in Cerebrospinal Fluid

People who experience episodes of major depressive disorder (MDD) are significantly more likely to have detectable HIV in their cerebral-spinal 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 2013) last week in Denver.

Although effective 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 favor specifically including such drugs in antiretroviral regimens, but others think that all guidelines-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 6 U.S. centers designed to evaluate neurocognitive and neuropsychiatric outcomes of HIV treatment.

The investigators used logistic regression and discrete-time survival models to examine the association 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 load 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/African-American. 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 or lowest-ever level was 149 cells/mm³. Half had a prior history of major depression episodes.

A subset of 212 participants who did not have detectable CSF viral load at study entry underwent at least 3 more spinal taps during follow-up to see if they experienced new-onset viral escape into their CSF.

Results

• 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 ratio 2.10).
• Among participants who did not have detectable CSF viral load at the start of the study, cumulative incidence of CSF viral escape over 18 months of follow-up (2,736 total person-months) was significantly higher among people with MDD compared to non-depressed participants (P<0.05):
• 6 months: 27 cases per 1,000 person-months among people with MDD vs 16 per 1,000 person-months among non-depressed participants;
• 12 months: 12 vs 19 cases per 1,000 person-months, respectively;
• 18 months: 12 vs 20 cases per 1,000 person-months, respectively.
• After controlling for other factors, the adjusted hazard ratio for new-onset CSF escape among people with MDD was 3.01, or 3 times higher.
• 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.

9/17/13

Reference

ER Hammond, RM Crum, GJ Treisman, et al. Major depressive disorder in persons with HIV is associated with new-onset of cerebrospinal fluid viral escape. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013). Denver, September 10-13, 2013. Abstract H-1257a.