HIV-positive smokers metabolise nicotine at a significantly higher rate than HIV-negative individuals, investigators from the United States report in the online edition of AIDS. The finding could explain why people with HIV have more difficulty quitting smoking than their HIV-negative peers. A second study involving the same HIV-positive smokers and published in the Journal of Acquired Immune Deficiency Syndromes showed that a higher nicotine metabolism ratio (NMR) was associated with symptoms of anxiety and treatment with efavirenz.

The researchers say their findings have important implications for the use of smoking cessation medication by individuals with HIV, and that more intensive therapy with varenicline (Chantix and Champix, an oral prescription medication), rather than nicotine replacement patches, is warranted.

“The mean NMR of this sample resembles levels reported among those with opioid dependence,” comment the authors. “Although the nature of the relationship between NMR and HIV is uncertain, these results suggest that the nicotine patch would have limited therapeutic benefit for most smokers with HIV, which has been reported, and that varenicline would be more beneficial.”

Glossary anxiety A feeling of unease, such as worry or fear, which can be mild or severe. Anxiety disorders are conditions in which anxiety dominates a person’s life or is experienced in particular situations. matched In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. body mass index (BMI) Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet. PLWH Short for people living with HIV. observational study A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

People with HIV are more likely to smoke and have more difficulty quitting than individuals in the general population. Smoking-related diseases are now a leading cause of serious illness and death among people with HIV and supporting smoking cessation should be part of routine HIV care.

The rate at which the body metabolises nicotine could explain why people with HIV are more likely to become smokers and find it harder to stop. Nicotine is metabolised by the body using the CYP2A6 liver enzyme. Research has shown that people with reduced CYP2A6 function (slow nicotine metabolisers) smoke fewer cigarettes, are less dependent on nicotine and are more likely to succeed in quitting smoking. NMR is a widely used measure of CYP2A6 function.

Investigators from the University of Pittsburgh hypothesised that smoking behaviours in people with HIV were influenced by NMR. They therefore designed an observational study comparing NMR between 131 HIV-positive smokers and 199 closely matched HIV-negative smokers.

Data were collected on factors known to impact on NMR, including sex, race, gender and body mass index (BMI).

Most of the participants were male (70-74%), African American (72-79%) and were living on an annual income below $35,000.

Almost all the HIV-positive participants were taking antiretroviral therapy (ART). Eighty per cent had an undetectable viral load and the average CD4 cell count was 714 cells/mm3.

The individuals with HIV smoked significantly fewer cigarettes daily than the matched population (13 vs 15, p = 0.003). Despite this, mean NMR was significantly higher in the people with HIV than the HIV-negative individuals (0.47 vs 0.39, p < 0.001).

Participants were divided into four groups according to NMR speed: people living with HIV were twice as likely as HIV-negative individuals to be placed in the fourth quartile, the fastest metabolisers (35% vs 17%).

“These findings suggest that HIV-infected smokers metabolize nicotine faster than HIV-uninfected smokers, even after controlling for relevant demographic and behavioral factors,” write the authors. “Understanding the mechanisms that contribute to faster nicotine metabolism among PLWH [people living with HIV] is necessary to understand tobacco’s role in undermining clinical outcomes in HIV, and identifying novel therapeutic interventions.”

The second study examined whether there were any specific characteristics associated with a higher NMR in the 131 HIV-positive people.

The investigators collected demographic data, information on CD4 cell count and viral load, CD4 cell count, ART type and adherence and symptoms of anxiety and depression. Breath carbon monoxide was also evaluated.

The initial analysis showed that race, symptoms of anxiety and depression, greater smoking intensity, breath carbon monoxide and therapy with efavirenz were all associated with higher NMR values.

After taking into account known potential confounders, a higher NMR remained associated with smoking more cigarettes per day (p = 0.050), higher levels of symptoms of anxiety (p = 0.054), and therapy with efavirenz (p = 0.003). Treatment with efavirenz accounted for 5% of the variance in NMR.

“Taking efavirenz was associated with higher NMR, rather than lower NMR as expected for a drug interaction (efavirenz would be predicted to inhibit CYP2A6), which needs to be understood further,” comment the authors. “This suggests that efavirenz therapy should be considered when addressing tobacco use among PLWH.”