Systematic review suggests smoking increases HIV infection risk

Smoking tobacco as an independent risk factor for progression to AIDS

A total of ten studies were identified that assessed whether smoking was associated with more rapid progression to AIDS. These were published between 1990 and 1999, and all took place in wealthy nations – Canada, the United Kingdom, Ireland, Norway and the United States – prior to the widespread availability of potent antiretroviral therapy.

Nine of these found no association, and the one study that did find an association was characterised by the reviewers as “one of the poorer quality studies.”

Nevertheless, they point out that “although not formally within the terms of this review, it is worth noting that two studies did note an association between smoking and the development of bacterial pneumonia” and “one of these also noted an association between smoking and increased risk of developing AIDS related dementia but a protective effect against Kaposi's sarcoma.”

It should be noted that in February 2005 - when the authors undertook their systematic review - the association between smoking and HIV disease progression was unclear. However, studies published before and since this review took place strongly suggest that smoking has both a direct and indirect impact on the life expectancy of HIV-positive individuals.

In particular, a large prospective observational study of HIV-positive women from the United States published in June 2006 found that cigarette smokers receiving antiretroviral therapy were significantly more likely to be diagnosed with an AIDS-defining condition or to die, negating some of the benefits of potent antiretroviral therapy. ^[1]

Although this paper does not refer to that study, the researchers do note that both HIV disease and smoking are associated with an increased risk of cardiovascular disease as well as lung disease. They also point out that “in developing countries where bacterial pneumonia might be less well treated and tuberculosis is more prevalent, smoking might be an important risk factor.”

A systematic review published online ahead of print publication in the journal Sexually Transmitted Infections suggests that smoking appears to be associated with an increased risk of acquiring HIV infection. However, although the review also suggests that smoking does not appear to be related to progression to AIDS, the authors point out several important limitations to their headline conclusions, including the fact that all of the studies examining the effects of smoking on HIV disease progression took place in the developed world prior to the widespread availability of potent antiretroviral therapy.

Smoking tobacco is known to be associated with immunological changes and an increased risk for certain infections in both HIV-negative and HIV-positive individuals, including the sexually transmitted infection (STI), human papilloma virus (HPV) , which is associated with genital and anal warts and cervical and anal cancer.

The authors of this review sought to ascertain whether studies published prior to 2005 had found an association between smoking and HIV infection, and smoking and HIV disease progression, as measured by an AIDS diagnosis.

In February 2005 they undertook a systematic review and found 15 papers: five of which examined HIV seroconversion and smoking; nine examined HIV disease progression and smoking; and one examined both.

More studies needed

The reviewers' assessment that smoking may increase the risk of HIV infection is provocative, particularly since this association has previously received little attention, possibly because so far no plausible biological mechanism adequately explains the increased risk, but also because all the studies published so far have not ruled out all the possible confounding factors. For example, smokers may be more likely to have a more cavalier attitude towards risk tha non-smokers, and this may affect sexual risk-taking - something that has not been measured in the studies that were reviewed.

Consequently, the reviewers call for further research “to investigate whether the association between smoking and HIV seroconversion is related to residual confounding.”

They also point out that “most studies identified in this review were set in developed countries” and that “future research must examine the effect of smoking on people living with HIV in developing countries where the AIDS epidemic has the greatest impact.”

Although smoking cessation is already an important public health measure in many nations, they conclude that “such research might add evidence to [further] inform decisions at population and individual levels.”

Smoking tobacco as an independent risk factor for HIV infection

Six studies assessed whether smoking was associated with an increased risk of acquiring HIV infection. Five studies – published between 1990 and 1996 in Haiti, the United States, Rwanda and Thailand – found that smoking was associated with somewhere between a doubling to a quadrupling increased risk of acquiring HIV infection in unadjusted analysis. Analyses adjusted for some confounding factors, however, revised the estimate to somewhere between a 1.6-fold and 3.5-fold increased risk.

However, the only truly prospective study to examine this association - from the United States' Multicentre AIDS Cohort Study (MACS) group and published in 1991 - concluded that smoking was not associated with an increased risk of acquiring HIV infection. This nested case-control study of 644 gay and bisexual men found that the adjusted risk was 1.22-fold, with a 95% confidence interval ranging between 0.99-1.50.

The reviewers assessed all six of the studies' strengths and weaknesses, and point out that although “the consistency of findings is striking” the methodology of the studies - which were epidemiological and observational - means that they are “unable to demonstrate causal relations and is prone to confounding.”

Although many of these confounding factors were addressed in most of the six studies, the reviewers point out that all of the studies relied on participants' self-reports to assess smoking status. “Current smoking status is possible to verify biochemically but none of the studies did this,” they write. “Whilst the fundamental potential risk factor is past rather than current smoking status, validation of current smoking status might have gone some way to confirming self-reported data.”

They also suggest that publication bias – a tendency to only publish studies that found an association between smoking and HIV acquisition – “cannot be ruled out.”

Nevertheless, they suggest that the link between smoking and becoming HIV-infected “could be a real effect.” In defence of this argument, they point out the theoretical risks – that smoking alters both cellular and humoral immunity – as well as the association of smoking with acquiring other infections, including other STIs. If this effect were real, they add “the size of the effect…would indicate a magnitude of public health importance.”