November 18, 2010
For children being treated for HIV in less developed countries, monitoring to predict the occurrence of serious HIV-related illnesses is most accurate if it includes a measure of HIV levels in the blood, according to a National Institutes of Health study conducted throughout Latin America.
Termed viral load, the quantity of human immunodeficiency virus (HIV) genetic material in the blood is a barometer of the effectiveness of HIV treatment. High viral loads indicate potential treatment failure, which can then lead to a weakened immune system and increased risk of infections.
Monitoring children's viral load is standard in the United States. However, the technology to perform viral load testing is difficult and expensive to maintain and, for these reasons, is often unavailable in less developed settings. Instead, in these settings, clinical symptoms or immune cell number are used to monitor the effectiveness of therapy. The current study is the first to assess the value of adding viral load to monitoring of symptoms and tests of immune function in children receiving anti-HIV treatment in a less developed setting.
The study authors noted that, in resource poor settings, shipping blood samples to a central facility where viral load levels could be measured might provide a cost effective alternative to performing viral load measurements at each clinical care site.
The researchers found that a viral load of 5,000 copies per milliliter of blood predicts a higher risk of serious illness in children on HIV treatment, providing clinical evidence for new World Health Organization recommendation (www.who.int/hiv/pub/paediatric/infants2010/en/index.html) on when to change HIV medications when it appears that a child's HIV treatment is failing.
"Our study showed that adding viral load monitoring would significantly improve the monitoring regimen used to safeguard the health of children being treated for HIV." said George K. Siberry, M.D., M.P.H., senior author of the study. Dr. Siberry is a medical officer in the Pediatric, Adolescent and Maternal AIDS Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute that funded the research.
The authors noted that using dried blood spots for viral load testing might provide a cost effective alternative to routine viral load testing methods. Although they did not evaluate this alternative in their study, the authors cited earlier research, of blood spots collected on filter paper. The authors noted that blood spots could be readily used to detect viral load at the level that predicted clinical illness in the current study. Filter paper, such as that used for newborn screening programs in the United States, could be used to collect blood samples in remote or poor areas, which could then be shipped to a central facility where they could be processed reliably and economically.
The study was led by first author Ricardo Oliveira, of the Federal University of Rio de Janeiro. He collaborated with colleagues at the University of Sao Paulo, University of Caxias do Sul, Federal University of Sao Paulo and the Emilio Ribas Institute of Infectious Diseases, all in Brazil, as well as researchers at Westat and the NICHD. The study was undertaken as part of the NICHD International Site Development Initiative (NISDI).
"The NISDI pediatric protocol follows HIV-infected children in Latin America as a way to learn more about the impact of the infection and its treatment on children while also helping to build clinical research infrastructure," explained NISDI principal investigator Dr. Rohan Hazra. The findings were published online in the journal Clinical Infectious Diseases.
To conduct the study, the researchers analyzed the medical records of 600 children with HIV who were receiving treatment at hospitals in Brazil, Mexico and Peru. The children were under age 15 and had been on anti-HIV medication for at least six months.
The children's viral load levels were monitored every six months, along with counts of CD4 white blood cells (to measure immune strength) and oxygen-carrying molecules (hemoglobin) in red blood cells. The children's growth and development were also followed.
The researchers sought to determine whether the most recent measurements of viral load could predict serious HIV-related illnesses, classified by the World Health Organization as stage 3 and 4 events (www.womenchildrenhiv.org/wchiv?page=charts-00-02). Stage 3 and 4 events are the most serious of the HIV-related illnesses that affect people whose immune systems have been weakened by the virus. The research team evaluated the predictive value of two viral load levels: 400 copies of viral genetic material per milliliter of blood and 5,000 copies per milliliter. The team also analyzed the added risk of incremental increases in viral load.
The research team found that the measure of a child's most recent viral load was the most effective for predicting illness, especially when the level was above 5,000 copies per milliliter. Above this threshold, a child had nearly twice the risk of developing a WHO stage 3 or 4 event. The researchers found that this prediction was independent of CD4 cell and hemoglobin levels in the blood as well as the child?s body mass index. A combination of all three measurements most accurately predicted impending illness.
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