[pronut-hiv] Cigarette smoking may undermine benefits of potent antiretroviral therapy

["Pronut-HIV" <pronut-hiv@halthnet.org>]

Aidsmap

Cigarette smoking may undermine benefits of potent antiretroviral
therapy 


Cigarette smokers are more likely to be diagnosed with an AIDS-defining
condition or to die, negating some of the benefits of potent
antiretroviral therapy, according to a large prospective observational
study of HIV-positive women from the United States. The study, published
in the June issue of the American Journal of Public Health, is the first
to find a relationship between smoking and HIV disease progression in
women. 

Until recently, there had been no studies on the effects of cigarette
smoking in the era of potent antiretroviral therapy. Data from Galia and
colleagues from the gay men's Multicenter AIDS Cohort Study had
previously found no association between smoking and the risk of
developing AIDS or dying, but since this was conducted prior to the
availability of potent anti-HIV therapy, it was possible that the
effects of smoking were masked by HIV's virulence. 

Last year, Crothers and colleagues published data from a large
prospective observational cohort of 867 HIV-positive male veterans which
found that smokers on potent antiretroviral therapy were twice as likely
to die than non-smokers, and more likely to suffer from increased
respiratory symptoms, chronic obstructive pulmonary disease (COPD), and
bacterial pneumonia. 

Recent studies have found that HIV-positive women who smoke are twice
as likely to acquire bacterial pneumonia, and three times more likely to
acquire human papilloma virus (HPV) , which can lead to cervical cancer,
an AIDS-defining condition. 

In order to investigate whether smoking affects disease progression and
death in women on potent antiretroviral therapy, investigators from the
Women's Interagency HIV Study (WIHS) analysed data from their
longitudinal cohort study of HIV infection among women enrolled at six
urban sites in the United States. 

Of the 2,059 women in the cohort, 56% were current smokers and 16% were
former smokers. At enrolment, the typical WIHS smoker had smoked a pack
of cigarettes a day for a median of 12.4 years - about a third of her
lifetime. 

A total of 924 women were eligible for this analysis. To be eligible,
an HIV-positive woman must have initiated potent antiretroviral therapy,
and have CD4 count, viral load and smoking data available. 

During the median 5.2 years of follow-up, around 524 women (57%)
reported being current smokers. The investigators found that there were
significant differences between smokers and non-smokers at baseline.
Smokers were more likely to be African American; more likely to have
used illicit drugs; had a lifetime history of illicit injection drug
use; were more likely to be infected with hepatitis C virus; and were
more likely to have previously been diagnosed with AIDS (all p=0.001). 

In addition, they found that mean CD4 counts were significantly higher
among smokers than non-smokers (539 vs. 517 cells/mm3; p=0.005),
although this difference was not seen with viral load levels. However,
over time, smokers' CD4 counts became lower than those of non-smokers
(p=.01 for trend). The investigators attempt to explain this by saying
that this may "reflect a selection bias in which healthier patients are
more likely to smoke at any point in time." However it is known that
HIV-negative smokers have higher CD4 lymphocyte levels, suggesting that
selection bias may not explain this observation. 

There were a total of 164 deaths during the observation period, and the
investigators found that smokers had a 53% increased risk of dying
compared with non-smokers (p=0.018), after adjusting for age, race, CD4
count, viral load, illicit drug use, previous AIDS, previous
antiretroviral use, baseline hepatitis C infection, and baseline
exposure category. 

Smokers also had a 36% increased risk of of developing an AIDS-defining
illness (p=0.01). However, the risk of AIDS-related deaths did not
differ between smokers and non-smokers. 

Since the investigators found that adherence to antiretroviral therapy
was significantly lower among smokers than among non-smokers, in order
minimise the potentially confounding effects of adherence they further
limited their analysis only to women who reported greater than 95%
adherence during the observational period. Nevertheless, differences
between smokers and non-smokers in the risk of death and AIDS-defining
conditions remained statistically significant. 

The investigators say that their data "clearly demonstrated that
HIV-positive women who smoke have a higher risk of acquiring
[AIDS-defining illnesses] or dying." They add that potent antiretroviral
therapy "is not as beneficial in smokers as it is in non-smokers." 

Whilst this may be related in part to adherence, they argue, "even
after adjustment for reported compliance and illicit drug use, [potent
antiretroviral therapy] was still less effective in smokers as measured
by AIDS incidence and death. These data indicate a negative impact of
smoking even while [potent antiretroviral therapy] may be effective in
reducing AIDS-related deaths in smokers." 

However the investigators are not sure why there was a lack of an
association between smoking and AIDS-related deaths. It may be due to an
"inability to determine the true cause of death in this cohort setting
or because competing causes of death result in smokers dying more
rapidly (i.e. smokers die from acute causes such as drug overdoses,
homicides/suicides/accidents before dying from AIDS-related causes)". It
may also be the case that whilst smoking has an impact on AIDS-defining
illnesses - such as cervical cancer and recurrent bacterial pneumonia -
they did not result in death during the observation period. 

Although the investigators controlled for important confounding factors
like adherence and for illicit drug use, they concede that there "may
still be some residual confounding factors not yet identified...We
cannot exclude potential bias among patients in poor health who may be
more or less likely to smoke. For example, a patient in poor health who
feels that she has nothing to lose might choose to smoke anyway, in
spite of the known health risks." 

Nevertheless, they conclude by saying that their "data suggest that the
treatment of HIV-positive women with [potent antiretroviral therapy] may
be less effective in those who smoke cigarettes and point to a need to
promote smoking cessation." 

References 
Feldman JG et al. Association of cigarette smoking with HIV prognosis
among women in the HAART era. Am J Public Health 96(6): 1060-1065, 2006.


Crothers K et al. The impact of cigarette smoking on mortality, quality
of life, and comorbid illness among HIV-positive veterans. Journal of
General Internal Medicine 20 (12), 1142-1145, 2005. 

Galai N et al. Effect of smoking on the clinical progression of HIV-1
infection. J Acquir Immune Defic Syndr Hum Retrovirol 14: 451-458, 1997.