SUMMARY: Cigarette smoking was associated with a significantly higher rate of cardiovascular disease among people with HIV, but the risk began to decline after quitting and continued to fall over time, researchers reported at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last week in San Francisco. A similar pattern was not seen for overall mortality, however.

By Liz Highleyman

As people with HIV live longer thanks to effective antiretroviral therapy (ART), they are at increased risk for a host of chronic non-AIDS conditions including cardiovascular disease and cancer.

While ongoing HIV replication, immune activation, and ART all contribute in ways that are not fully understood, modifiable lifestyle factors such as smoking also play a large role. Numerous studies have found that HIV positive people are more likely to smoke than their HIV negative counterparts.

Kathy Petoumenos (Photo by Liz Highleyman)

Past research has shown that the risk of coronary artery disease falls within 1-2 years after smoking cessation in HIV negative people. Kathy Petoumenos and fellow investigators with the D:A:D cohort designed a study to see if rates of cardiovascular disease and death would also decrease for HIV positive people who quit.

D:A:D (Data Collection on Adverse events of Anti-HIV Drugs) is a large, ongoing observational study with 33,308 HIV positive participants in the U.S., Europe, and Australia. The researchers divided the participants into groups according to smoking status: 36% were current smokers, 27% had never smoked, and 19% were former smokers. In addition, one-quarter (8197 individuals) said they quit after entering the study. (There was not enough data to evaluate smokers based on packs per day or number of years smoking.)

Most participants (about 75%) were men, about half were white, and the average age was about 40 years. There were more injection drug users in the current and ex-smoker groups (32% and 18%, respectively) compared with the never-smokers (5%). Most were on combination ART, with an average duration of about 1.5 years; more than 60% had HIV viral load < 50 copies/mL and the median CD4 cell count was approximately 450 cells/mm3.

Participants in the different smoking status groups were similar with regard to other traditional cardiovascular risk factors including body weight (generally normal, with an average BMI of about 23), blood pressure (again normal), and blood lipid levels.
The researchers looked at clinical outcomes including myocardial infarction (MI, or heart attack), coronary heart disease (MIs plus invasive coronary artery procedures or death from other coronary heart disease), cardiovascular disease (a broader category including coronary heart disease plus carotid artery endarterectomy or stroke), and deaths due to all causes. They determined event rates for the different smoking status groups and compared them to derive incidence rate ratios (IRRs).

Results

	Current smokers had more than 3 times the risk for MIs (IRR 3.4) and ex-smokers approached 2 times the risk (IRR 1.73) compared with people who never smoked.
	Among participants who quit smoking during follow-up, excess MI risk decreased from 3.73-fold higher during the first non-smoking year, to 3.00-fold after 1-2 years, to 2.62-fold after 2-3 years, and finally to 2.07-fold after more than 3 years without smoking.
	For coronary heart disease, current smokers had about a 2.5-fold risk (IRR 2.48) and ex-smokers a 1.6-fold risk (IRR 1.60) compared with people who never smoked.
	Among participants who quit, excess coronary heart disease risk decreased from 2.93-fold higher during the first non-smoking year, to 2.48-fold after 1-2 years, 1.90-fold after 2-3 years, and 1.83-fold after more than 3 years.
	Looking at cardiovascular disease overall, current smokers had 2.19-fold higher risk relative to non-smokers, and ex-smokers had a 1.38-fold higher risk.
	Again, excess risk declined steadily among people who quit during the study, from 2.32-fold higher during the first year, to 1.84-fold after 1-2 years, 1.60-fold after 2-3 years, and 1.49-fold after more than 3 years.
	For all-cause mortality, however, the pattern was somewhat different. The risk of death was 1.28 higher among current smokers, but former smokers had essentially the same risk as people who never smoked (IRR 0.99).
	Among people who quit smoking during the study, the excess risk of death did not decline consistently over time (from 1.67-fold higher during the first year to 1.02-fold after 1-2 years, 1.34-fold after 2-3 years, and 1.30-fold after more than 3 years).
	A similar inconsistent pattern was also see when the analysis was restricted to deaths of people older than 50 years.
	People who never smoked were more likely to die form HIV/AIDS-related causes, while current and previous smokers were more likely to have other causes of death including cardiovascular disease and non-AIDS malignancies.

Based on these findings, the researchers concluded, "The risk of cardiovascular disease events in HIV-positive patients decreased with increasing time since stopping smoking." However, they added, "we did not see this in terms of mortality."

Another study presented at CROI found that people with HIV had a higher rate of lung cancer, and smoking was by far the strongest risk factor. After 8 years of follow-up -- more than twice as long as this D:A:D analysis -- ex-smokers still had a 5-fold greater lung cancer risk.

"Smoking cessation efforts should be a priority in the management of HIV-positive patients," the D:A:D investigators recommended. "Further research is needed regarding smoking cessation in this population."

National Center in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; Copenhagen HIV Program, Hvidovre University Hospital, Copenhagen, Denmark; HIV Monitoring Foundation, Academic Medical Center, Amsterdam, Netherlands; Ctr Hosp Univ Saint-Pierre, Brussels, Belgium; ICONA, Azienda Ospedaliera-Polo Univ San Paolo, Milan, Italy; Univ Hosp Zurich, Switzerland; INSERM E0338 and U593, Univ Victor Segalen Bordeaux, France; Ctr Hosp Univ Nice, Hosp de l'Archet, France.

2/26/10

Reference
K Petoumenos, S Worm, P Reiss, and others (D:A:D Study Group. Rates of Cardiovascular Disease Following Smoking Cessation in Patients with HIV Infection: Results from the D:A:D Study. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 124.