A new study vice-chaired by Dartmouth-Hitchcock Medical Center pediatrician Paul Palumbo may cause changes to standard AIDS treatment strategies around the world.
Palumbo presented the International Maternal Pediatric Adolescent AIDS Clinical Trials group study which demonstrated that an alternative AIDS treatment administered to children of HIV-positive mothers was significantly more effective than the most common treatment at the Conference on Retroviruses and Opportunistic Infections in Boston last week, Palumbo said in an interview with The Dartmouth.
The study, known as "P1060" compared the effectiveness of two anti-retroviral drugs, Nevirapine and Kaletra, in treating HIV-positive children between the ages of six months and three years, according to Palumbo.
The first phase of the study compared the effectiveness of Nevirapine and Kaletra in children who had previously taken Nevirapine and whose mothers had also taken Nevirapine during labor to reduce the risk of HIV transmission from mother to child, according to a Dartmouth Medical School press release. The second phase compared the same two drugs in children who had not received Nevirapine at birth, according to the press release.
The first phase of the study concluded in April 2009, before its estimated completion date, because the results clearly demonstrated that Kaletra performed much better than Nevirapine, The Dartmouth previously reported. These findings resulted in a revision of the World Health Organization guidelines to recommend the use of Kaletra in the treatment of pediatric HIV patients, Palumbo said.
The second phase of the study was completed in October 2010, again ahead of its target completion date of March 2011. The National Institutes of Health's Data and Safety Monitoring Board concluded that no further testing was necessary to prove the superior effectiveness of Kaletra, according to Palumbo. Of the children involved in this phase of the study, only 12.3 percent of the children taking the Kaletra treatment failed to sufficiently suppress the HIV virus in their systems or died during treatment compared to 28.6 percent of those taking the Nevirapine regimen, according to a press release from the National Institute of Allergy and Infectious Diseases.
Researchers had hoped that Nevirapine would prove most effective in treatment of children never before exposed to HIV because the drug is cheaper and more "temperature-tolerant" than Kaletra, Palumbo said. Nevirapine also combines three necessary medications into one single liquid or pill dosage, while Kaletra requires three separate doses, he said.
As a result of the trial's findings, the WHO has begun to consider further adjustment of its pediatric treatment guidelines, according to Palumbo. Palumbo met confidentially with WHO representatives twice to discuss the findings before the conference last week, he said.
Although the WHO agreed that IMPAACT's results "warrant expanding the guidelines," Palumbo said the feasibility of using Kaletra, the more-expensive drug, had to be considered before a decision could be made. The previous guideline revisions have yet to be implemented outside of South Africa and Botswana, he said.
"I think there is a push for [the WHO] to try and reach a decision by the summer, or by the end of the summer," Palumbo said. "It's playing out literally as we speak."
The Data and Safety Monitoring Board is "very rigorous and very demanding," David Shapiro, director of the IMPAACT Statistical and Data Management Center, said in an interview with The Dartmouth. The Board assesses all findings "with a fine-toothed comb" to ensure accuracy, he said.
Researchers offered the children who had been treated with the less-effective Nevirapine treatment the chance to switch to the better-performing Kaletra, Palumbo said.
The IMPAACT study was initiated because researchers wanted to investigate the use of Nevirapine to prevent transmission of HIV from mothers to their children which Nevirapine does in about 50 percent of cases and its use as a treatment for children who still contract the virus after birth, according to Palumbo.
"In resource-limited settings, [Nevirapine] has become the gold standard for preventing mother-to-child transmission of HIV," he said.
This treatment method has an "Achilles' heel," however, because HIV eventually becomes resistant to Nevirapine treatment, according to Palumbo. This problem prompted researchers to inquire about the effectiveness of other drugs to treat HIV-positive children, he said.
Palumbo, who has been involved with IMPAACT since the 1980s, said he is continuing to work with the results of this study.
"We have to do more analyses," he said. "We're looking at blood samples from children in the study to ascertain the levels of drugs that are in their samples, as well as looking at the characteristics of the virus in their blood."
