“ Research in our laboratory had found that persons with HIV (PWH) who were chronic tobacco smokers had greater cognitive deficits and psychiatric symptoms, as well as greater white matter abnormalities on diffusion tensor imaging,” explains Linda Chang, MD, MS, FAAN, FANA. “The white matter abnormalities indicate neuroinflammation and fiber tract damage, which could lead to both cognitive deficits and brain atrophy.”

Tobacco smoking has remained high over the past decade, Dr. Chang notes, and has been linked to cognitive deficits in the general population. “However, very few studies examined the combined effects of chronic tobacco smoking and HIV on the brain,” she says. “Most prior studies only explored the additive effect of tobacco smoking and HIV infection.”

For a study published in AIDS, Dr. Chang and colleagues used a 2-by-2 design, enrolling smokers with HIV, non-smokers with HIV, smokers without HIV, and non-smokers without HIV. “This 2-by-2 design can evaluate the independent, by separately comparing HIV-seronegative smokers versus HIV-seronegative non-smokers, and combined effect, by comparing smokers with HIV and non-smokers with HIV, of HIV and tobacco smoke,” she explains.

Cognitive Function Worst Among Smoke With HIV

The study included 83 PWH (43 non-smokers; 40 smokers) and 171 HIV-seronegative individuals (106 non-smokers; 65 smokers). “All PWH were on stable antiretroviral treatment,” says Dr. Chang. “The two smoker groups were active smokers and had smoked tobacco cigarettes for 16-20 pack-years.”

Regardless of smoking status, and relative to seronegative individuals, PWH had smaller brain volumes, specifically in reference to the basal ganglia, thalami, hippocampi, subcortical gray matter, and cerebral white matter volumes (P=0.002-0.042), steeper age-related decreases in the right superiorparietal region volumes (interaction, P<0.001), and poorer attention/working memory and learning (P=0.016-0.027). In addition, regardless of serostatus, smokers often had smaller hippocampi than non-smokers. PWH smokers had the smallest total and regional subcortical gray matter and cortical white matter volume and weakest cognitive functioning.

“Those who had both HIV and were chronic tobacco smokers performed the poorest across the four participant groups,” says Dr. Chang. “The takeaway message is that chronic tobacco smoking and HIV infection have additive deleterious effects on various cognitive domains, especially with attention and learning (Figure).”

Directions for Future Research

The study results indicate that the clinical management of HIV should include cognitive assessments, Dr. Chang says, particularly when the PWH is a tobacco smoker. Additionally, tobacco smoking cessation “should be emphasized and included as an approach to improve cognitive and mental health in the clinical management of HIV disease.”

Many questions remain “that need to be answered,” Dr. Chang continues. These questions include whether smoking also leads to more rapid cognitive decline or brain atrophy with aging among PWH; whether cognitive deficits or brain atrophy would improve with tobacco smoking cessation; whether replacement products, such as electronic tobacco products or even nicotine patches, induce similar adverse effects on the brain in PWH; and whether the greater brain atrophy and cognitive deficits seen in PWH who are smokers are mainly due to greater neuroinflammation.

“Since brain MRI cannot provide direct measures of neuroinflammation, future studies should include plasma or cerebrospinal fluid biomarkers for neuroinflammation or other neuroimaging techniques, such as magnetic resonance spectroscopy and PET with tracers that can assess glial activation, to evaluate whether chronic smoking exacerbates neuroinflammation in PWH,” Dr Chang says.