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.”
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.”