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  16th CROI
Conference on Retroviruses and Opportunistic Infections Montreal, Canada
February 8-11, 2009
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Smoking Emerges as Top Death Risk Factor in FRAM Participants With HIV
  16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal
Mark Mascolini
Current smoking proved the major modifiable death risk factor among HIV-infected people enrolled in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study [1]. Lower CD4 count and older age also made death more likely among HIV-infected FRAM participants in this 2004-2007 follow-up of a study that began in 2000. FRAM famously isolated peripheral and central fat atrophy (not fat accumulation) as the distinguishing feature of HIV lipodystrophy by comparing HIV-infected people with a non-HIV heart study cohort [2].
FRAM enrolled 1183 HIV-infected men and women from 16 US clinics from June 2000 to September 2002. At the same time, the trial recruited 297 controls without a positive HIV test from two centers of the Coronary Artery Risk Development in Young Adults (CARDIA) study. The new analysis involved 922 HIV-infected people and 280 CARDIA controls who had a follow-up exam from 2004 to 2007 and were known to be alive or dead after that. Statistical comparisons between the HIV group and controls focused on people between 33 and 45 years old. These analyses excluded HIV-infected people with an opportunistic infection or malignancy in the month before their original FRAM exam.
Compared with CARDIA controls, the HIV group included a much higher proportion of current smokers--48% versus 17%. While 6% of the HIV group had diabetes, 3% of control did. On the other hand, HIV-infected FRAM participants had a slightly lower average systolic blood pressure (113 vs 116 mm Hg) and lower total cholesterol (191 vs 196 mg/dL). But the HIV contingent also had a much lower average "good" high-density lipoprotein (HDL) cholesterol (41 vs 51 mg/dL). Comparing mortality risk in 469 HIV-infected people and 280 controls between the ages of 33 and 45, the FRAM team calculated a 7 times higher death risk in the HIV group (P < 0.0001). When the researchers adjusted the analysis for gender, age, and ethnicity, the death risk remained 7 times higher in HIV-infected people (P < 0.0001). After traditional cardiovascular risk factors got factored into the calculation, the death risk remained 3.4 times higher in people with HIV (P = 0.009).
Next the researchers split the HIV cohort into three current CD4 count strata--more than 350, 200 to 350, and under 200. After adjustment for other risk factors, 245 people with more than 350 CD4s had a 2.3 times higher risk of death than HIV-negative controls, but that difference lacked statistical significance. People with lower CD4 counts did have a significantly higher risk of dying than controls--4.3 times higher (95% confidence interval [CI] 1.14 to 16.0) in 114 people with 200 to 350 CD4s, and 6.3 times higher (95% CI 2.2 to 18.2) in 105 people with fewer than 200 CD4s.
Finally, the FRAM investigators weighed the impact of demographics (gender, race, age), HIV-related factors (current CD4 count, detectable viral load, AIDS, hepatitis C virus infection), and traditional death risk factors (smoking, diabetes, systolic and diastolic blood pressure, and HDL and non-HDL cholesterol) on mortality only in people with HIV.
Current smoking (but not past smoking) nearly tripled the death risk (hazard ratio [HR] 2.73, 95% CI 1.64 to 4.53, P = 0.0001). Every added 10 years of age raised the risk more than 60% (HR 1.61, 95% CI 1.27 to 2.05, P < 0.0001). And every log2 higher current CD4 count lowered the risk 35% (HR 0.65, 95% CI 0.58 to 0.73, P < 0.0001). The link between current smoking and death held true in all three CD4 count strata.
The higher risk of death conferred by HIV even in people with a CD4 count above 350 led the researchers to endorse the hypothesis that chronic HIV-induced inflammatory changes boost the risk of death.
1. Modrich L, Scherzer R, Zolopa A, et al. Factors associated with mortality in the study of Fat Redistribution and Metabolic Change in HIV Infection. 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal. Abstract 706.
2. Bacchetti P, Gripshover B, Grunfeld C, et al. Fat distribution in men with HIV infection. Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). J Acquir Immune Defic Syndr. 2005;40:121-31.