October 31, 2011 (Belgrade, Serbia) — Among HIV-positive men who have sex with men (MSM), AIDS-related mortality dropped sharply between 2004 and 2011, but non-AIDS mortality has not decreased in this group.
A Swedish cohort of these men had 4-fold higher mortality than would be expected for the corresponding Swedish male general population, Amani Eltayb, Vet Bsc, PhD, a postdoctoral researcher in the Department of Neurobiology, Care Sciences and Society at the Karolinska Institute in Stockholm, Sweden, told delegates here at the 13th European AIDS Conference of the European AIDS Clinical Society (EACS). The only independent predictors of mortality that she found were smoking and insulin resistance.
In a 12-year follow-up study, the use of highly active antiretroviral therapy (HAART) greatly reduced the incidence of AIDS and AIDS-related mortality. HAART was introduced in Sweden in 1996, and severe side effects started to emerge a few years later. So Dr. Eltayb and coworkers investigated the long-term mortality and predictors of mortality among HIV-positive MSM.
The cohort they followed (n = 346) had a mean age of 40 years at the start of the study period (enrollment in 1998-2000) and had been infected with HIV for a median of 8 years; 17% developed AIDS. Three quarters of them were receiving protease inhibitor therapy, 50% had received stavudine, 51% had received didanosine, and 60% were smokers.
During the study period, 45 patients (14%) died, and 30 were lost to follow-up. "The total mortality was 1.09/100 patients per year, which includes AIDS-mortality of 0.14/100 patients per year, while non-AIDS mortality represents 0.94/100 patients per year," Dr. Eltayb reported. Causes of death were determined from patient records and postmortem examinations.
Comparing mortality and its causes in 2004 with the figures for 2011, she said for total mortality in 2011 "there is a substantial decrease, which is mainly due to the AIDS-related mortality" decreasing from about 0.9/100 patients per year to about 0.15/100 patients per year. Over the time period, the non–AIDS-related mortality was fairly constant, dropping from about 1.0/100 patients per year to 0.9/100 patients per year.
Dr. Eltayb said the mortality among HIV-positive MSM was 4-fold higher than in the corresponding Swedish general population in Stockholm. Of the 45 total deaths, 6 (14%) were attributable to AIDS-related malignancies or infections, and the rest were attributable to non–AIDS-related causes: 11 (25%) from non-AIDS malignancies, 5 (11%) from hepatitis B or C, 6 (14%) from severe bacterial infections, 5 (11%) from cerebrovascular disease, 5 (11%) from suicide or trauma, and 7 (16%) from other causes.
According to single regression analysis, insulin resistance, a history of ever taking stavudine, and smoking were significant predictors of mortality. By multiple regression analysis, "smoking and insulin resistance are the only risk factors of mortality among this MSM cohort," Dr. Eltayb said. "This was quite interesting because neither lipids nor developing AIDS were significant risk factors."
Marta Boffito, MD, PhD, consultant physician at Chelsea Westminster Hospital in London, United Kingdom, who was not involved with the study, commented to Medscape Medical News, "I think it’s the interindividual variability in lipids. I’m not sure they did the right analysis to show anything about lipids. The analysis was probably well-designed for insulin resistance only."
She noted that diabetes is a known risk factor and "HIV and its treatment do alter metabolism… so I think that’s the already known cause behind insulin resistance [as a risk factor]."
Dr. Eltayb also found that smokers were 2.5-fold more likely to die (95% confidence interval [CI], 1.2 – 5.2; P < .016), and insulin resistance (fasting serum insulin > 100 pmol/L) conferred a 2.1-fold higher risk for death (95% CI, 1.0 – 4.1; P < .036).
She concluded that "despite diminishing AIDS because of the use of [antiretroviral therapy], the mortality is highly increased, and non-AIDS mortality has not decreased since 2004."
The investigators recommend that prevention and treatment of cardiovascular risk factors should be a high priority, with promotion of a healthy lifestyle (including smoking cessation), screening, early diagnosis, and treatment of malignancies for HIV-positive men. HIV-positive men and their healthcare providers should also be made aware of the shift in the disease spectrum as it applies to them.
Dr. Boffito commented that an important point that Dr. Eltayb and colleagues did not consider in this study was lifestyle. "She focused on MSM with HIV, but she didn’t look at MSM without HIV, which would be fundamental to see whether there are other factors that predispose to have high rates of insulin resistance in the MSM population, independently from HIV infection and antiretroviral treatment."
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