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RNA Spikes Predict Heart Disease, CD4s Predict Liver and Kidney Disease
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
HIV RNA spikes above 400 copies in people with an undetectable load predicted cardiovascular disease in a large Dutch cohort, while CD4 counts under 200 raised the odds of kidney or liver disease [1]. The investigators caution that the study's power to detect a link between blips and heart disease may be limited because of the relatively short follow-up during episodes of viremia above 400 copies.
ATHENA cohort investigators identified 6440 people who began combination antiretroviral therapy and reached a viral load below 50 copies within 48 weeks. No one had a non-AIDS diagnosis before starting treatment. The investigators defined four types of virologic "episodes" during regular follow-up in this prospective cohort study:
· Viral load below 50 copies: 10,873 episodes
· Low-level viremia between 50 and 400 copies: 3353 episodes
· High-level viremia above 400 copies: 1709 episodes
· Treatment interruption: 1029 episodes
The study group had a median age of 39 years, and median follow-up reached 3.9 years. Median CD4 count when antiretroviral therapy began stood at 200 and median viral load at 100,000 copies. During the study period the investigators recorded three clusters of non-AIDS events:
· 102 cardiovascular events including myocardial infarction, stroke, or invasive coronary procedures
· 72 episodes of acute or chronic renal failure
· 70 episodes of liver fibrosis or cirrhosis
Overall incidence of non-AIDS diagnoses fell from 2.2 per 100 person-years when the CD4 count stood below 200, to 1.06 with 200 to 350 CD4s, 1.01 with 350 to 500 CD4s, and 0.64 when the CD4 count stood above 500.
To uncover potential associations between virologic episodes and non-AIDS diagnoses, the investigators devised a statistical model that considered episodes of viremia, treatment interruptions, and CD4 count as time-updated variables, while adjusting for age, gender, diabetes, HBV/HCV coinfection, CDC stage, HIV transmission group, smoking, and alcohol use.
That model determined that viremic episodes above 400 copies almost tripled the risk of newly diagnosed cardiovascular disease compared with viral suppression (relative hazard [RH] 2.69, 95% confidence interval [CI] 1.29 to 5.63), independently of latest CD4 count. Neither high-level viremia, low-level viremia, nor treatment interruption predicted kidney or liver disease.
Compared with a CD4 count above 500, a count below 200 more than doubled the risk of liver disease (RH 2.33, 95% CI 1.04 to 5.25) and inflated the risk of kidney disease more than 11 times (RH 11.4, 95% CI 5.16 to 25.2).
Reference
1. Zhang S, van Sighem A, Gras L, et al. Episodes of HIV viremia and the risk of non-aids events among successfully treated patients. Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 503.
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