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No Higher Risk of Toxicity-Related ART Stops in Older People
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8th International Congress on Drug Therapy in HIV Infection
November 12-16, 2006
Glasgow, Scotland
Mark Mascolini
People older than 50 when starting antiretroviral therapy (ART) did not run a higher risk of stopping treatment because of side effects in an analysis of the 10-center UK CHIC cohort [1]. Older people did have higher rates of treatment-related hemoglobin abnormalities than their younger counterparts.
Caroline Sabin from London's Royal Free Centre for HIV Medicine and UK CHIC collaborators hypothesized that older people may have trouble tolerating antiretrovirals for two reasons. First, medical conditions that come with aging and the drugs used to treat those conditions may interfere with antiretroviral agents. And second, several studies show older people adhere better to antiretroviral regimens, so they may be exposed to higher levels of antiretrovirals than younger people. (note from Jules Levin: I would add that older people also may have a less healthy immune system which may reduce coping with side effects).
To test these theories, Sabin looked at 7932 antiretroviral-naive people beginning a potent regimen, including 693 (8.7%) older than 50. The older people were more likely to be white, gay, and men, and more likely to have lower CD4 counts and viral loads when starting therapy. But the older and younger groups did not differ much in type of antiretroviral regimen, specific antiretrovirals used, or year of starting therapy. Sabin and colleagues found that 1703 people with follow-up viral loads stopped the keystone "third" drug in their regimen because of antiretroviral-related toxicity. While the discontinuation rate was the same in older and younger people in the first half-year of treatment (4.4%), those rates climbed higher in older people over the following months: 10.7% versus 9.7% at 12 months, 17.7% versus 14.4% at 18 months, and 22.0% versus 17.9% at 24 months (P = 0.01).
An unadjusted statistical analysis determined that older people had a 23% higher risk of stopping antiretrovirals because of side effects than younger people (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.05 to 1.45, P = 0.01). The risk of stopping was highest from treatment year 2 onward (HR 1.33, 95% CI 1.09 to 1.62, P = 0.005). But after statistical adjustment for other variables--male gender, HIV risk group, ethnicity, calendar year of starting therapy, type of regimen, and pretreatment CD4 count and viral load--older people no longer had a significantly higher risk of stopping antiretrovirals because of toxicity at any point of follow-up (HR at 1 year 1.12, P = 0.45; HR from second year on 1.19, P = 0.13).
Compared with younger patients, older people had significantly higher triglycerides (P = 0.0001), total cholesterol (P = 0.0001), and alanine aminotransferase (P = 0.001), and significantly lower hemoglobins (P = 0.0002) before treatment began. Univariate analysis tied older age to abnormal triglycerides, cholesterol, and hemoglobin in the first year of antiretroviral therapy. After statistical adjustment for baseline demographics and pretreatment levels, the links between older age and high lipids during treatment lost statistical significance. But the correlation between older age and lower hemoglobin during treatment remained (odds ratio 1.62, 95% confidence interval 1.15 to 2.30, P = 0.006).
Sabin and colleagues concluded that higher toxicity-related discontinuation rates among older people "are largely explained by the demographic profiles and preexisting age-related changes in these individuals" before they start therapy. They also cautioned that their definition of toxicity-related treatment discontinuation (stopping therapy with a viral load under 50 copies) may overestimate the true rate of that phenomenon because it does not exclude stopping therapy for other reasons.
Reference
1. Sabin CA, Smith CJ, Hill T, et al. Is older age a risk factor for antiretroviral toxicities?
8th International Congress on Drug Therapy in HIV Infection, November 12-16, 2006, Glasgow. Abstract P160.
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