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Cumulative Viral Load Predicts Morbidity/Mortality in Perinatally Infected Children
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IDWeek, October 2-6, 2013, San Francisco
Mark Mascolini
Every 10-fold increment in viremia copy-years, a cumulative measure of viral load over time, raised the risk of illness and death 8.5 times in a study of 70 perinatally infected US children [1]. Higher viremia copy-years also predicted hospital admissions in this retrospective chart review.
HIV clinicians and researchers typically consider viral load as a cross-sectional (snapshot) value, but a single viral load says nothing about an individual's cumulative exposure of HIV replication over time. Viremia copy-years predicted all-cause mortality independently of one-time viral load measurements and time-updated CD4 count in 2027 antiretroviral-naive adults starting therapy [2]. To test the predictive value of viremia copy-years in children perinatally infected with HIV, researchers at Yale-New Haven Hospital conducted this study.
The Yale team considered children cared for in the hospital's Pediatric HIV Clinic between 1996 and 2012 who had three or more viral load measures. They extracted HIV-related and other clinical variables from medical records and calculated viremia copy-years as the number of copies of HIV RNA in plasma accumulated over time. The investigators used Cox proportional hazards modeling to identify predictors of the primary outcome, morbidity and mortality.
The analysis included 70 children, 37 boys and 33 girls. Two thirds of children were African American, 23% Hispanic, and 10% white. Forty-one children (59%) were in foster care or adopted. Study participants had a median 37 viral load measures each. During a median follow-up of 14.5 years, 16 children (23%) died to yield a death rate of 1.7 per 100 person-years. Only 2 children died before reaching the age of 10; most died in their early or late teens, and most died before 2003. These children had a median three hospital admission and a median 1.46 AIDS diagnoses. Nineteen children (27%) had one AIDS diagnosis and 8 (11%) had two or three AIDS diagnoses.
Eighteen study participants (26%) had a viremia copy-years level below 4 log10 (10,000 copies), 33 (47%) had a level between 4 and 5 log10 (10,000 to 100,000), and 19 (27%) had a level above 5 log10. No children with fewer than 10,000 viremia copy-years died, 4 (12%) with 10,000 to 100,000 copy-years died, and 12 (63%) with more than 100,000 copy-years died (P < 0.0001). Every 10-fold (log10) higher viremia copy-years conferred a 15-fold higher risk of death (95% confidence interval [CI] 4.20 to 53.4).
Each 10-fold higher viremia copy-years was strongly associated with more hospital admissions and number of new AIDS diagnoses (P < 0.0001). Median numbers of hospital admission were 1.5 in children with fewer than 10,000 viremia copy-years, 2 in children with 10,000 to 100,000 copy-years, and 6 in children with more than 100,000 copy years (P = 0.002). For the same three groups, median numbers of AIDS diagnoses were 1, 1, and 3 (P = 0.007).
After statistical adjustment for most recent CD4 count, gender, and race, every 10-fold higher viremia copy-years raised the risk of morbidity and mortality 8.5 times (hazard ratio 8.5, 95% CI 2.1 to 34.3, P = 0.003).
The investigators proposed that "viremia copy-years could serve as a surrogate measure of an individual's HIV disease activity and a predictor of subsequent HIV and non-HIV associated diseases." They speculated that, by measuring cumulative HIV burden, viremia copy-years "is a good indicator of continuous immune activation and its untoward complications." Until a functional cure for HIV can be found, the Yale team suggested, the goal of antiretroviral therapy should be to keep viral load undetectable at all times.
References
1. Thorvaldsson O, Paintsil E, Northrup V, Andiman W. Cumulative viremia-copy years predicts morbidity and mortality in perinatally HIV-infected children. IDWeek 2013. October 2-6, 2013. San Francisco. Abstract 412.
2. Mugavero MJ, Napravnik S, Cole SR, et al. Viremia copy-years predicts mortality among treatment-naive HIV-infected patients initiating antiretroviral therapy. Clin Infect Dis. 2011;53:927-935. http://cid.oxfordjournals.org/content/53/9/927.long........http://www.natap.org/2011/HIV/102011_01.htm
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