Apr. 2, 2002 In the largest long-term study of HIV-infected infants and children to date, UCLA AIDS Institute researchers discovered that African strains of the virus infected two American infants as early as 1994. The results are published in the April issue of AIDS Research and Human Retroviruses.
The scientists also found that multi-drug “cocktails” — available for children only since 1997 — successfully combat the spread of HIV in most pediatric patients. However, the more complicated regimens work best —posing a host of social problems as these children enter adolescence. These findings are published in the April edition of Clinical Infectious Diseases.
“The good news is that HIV-infected children can safely take these complex drug combinations,” said Dr. Paul Krogstad, UCLA associate professor of pediatrics and pharmacology and a member of the UCLA AIDS Institute. “The bad news is that U.S. medical lab tests may be overlooking evidence that overseas viral strains are affecting American children,” he said.
African HIV strains infect two children
Krogstad and his colleagues discovered that two of the American children in the UCLA study possessed HIV strains commonly found in Africa. The research team discovered the African strains while analyzing the genetic profile of the virus in children who had developed resistance to anti-HIV drug regimens.
One infant carried the African strain D and the other had contracted a type that combined African viral strains A and G. The children’s mothers had transmitted the AIDS virus to them during their births in the United States in the mid 1990s. In the United States and Western Europe, viral strain B causes most HIV infections.
The scientists’ original tests showed that both children had responded well to the antiviral drugs. At the end of the year, however, the team remeasured the children’s viral loads with another diagnostic method designed to detect non-B viral strains.
Not only did the researchers discover that the two children carried African strains of HIV, but the readings of the child with the A/G strain revealed a viral load more than 100 times higher than the original test.
“We’d considered this child a medical success story — but his readings went through the roof,” Krogstad said. “He was in much worse shape from the beginning than we’d realized.”
The research team had believed the child possessed a mild case of HIV that was completely suppressed by the drugs, Krogstad said. In reality, the boy had a poorly controlled infection that responded more slowly to medication than the other children in the study.
“We underestimated the severity of this child’s disease for a year,” Krogstad said. “We didn’t treat his case as aggressively as we could have because we thought his viral load didn’t require it. This may have allowed his infection to progress.”
Inconsistent lab results overlooked
The UCLA finding suggest that the diagnostic methods most commonly used by U.S. hospitals in the past may have inaccurately measured other Americans’ HIV infections. The UCLA study emphasizes that AIDS clinicians must be trained to look for non-B viral strains in their practices in order to prevent and treat mother-to-child HIV transmission.
“Physicians need to watch for scenarios where lab tests disagree,” Krogstad said. “For example, when low T-cell counts don’t coincide with undetectable viral loads in the blood. This likely signals a different viral strain.”
Children enrolled at 50 sites
For one year, Krogstad and his associates followed 181 infants and children whose HIV-positive mothers had transmitted the virus to them at birth. Treated at 50 sites throughout the United States and Puerto Rico, the children ranged from 4 months to 17 years. Sixty-two percent were African American, 28 percent were Latino and 10 percent were Caucasian.
The researchers randomly divided the children into four groups and treated each group with a different combination of powerful HIV-fighting drugs called protease inhibitors and reverse transcriptor inhibitors. One regimen combined four medications, and the other three regimens combined three medications. None of the children had taken these drugs before.
Four-drug regimens worked better
After one year, the researchers compared the regimens’ outcomes. While all four regimens ultimately reduced the virus to undetectable levels in the blood in half of the children, the four-drug combination produced more lasting results.
The four-drug regimen also helped more children. In the four-drug group, 52 percent of the children maintained undetectable viral levels. In the three other groups, the drugs suppressed the virus to undetectable levels in only 30 percent to 42 percent of the children.
“The four-drug regimen clearly controlled the virus the best – but it’s also the hardest for children to follow,” said Krogstad, an Elizabeth Glaser Pediatric AIDS Foundation scientist. “Parents and physicians must weigh the benefits of these medications against the day-to-day interruptions they cause in a child’s life.
“HIV is still a stigmatized disease in the United States,” he said. “After a lifetime of chronic illness, these children often stand out in adolescence because they are the smallest. Adolescence is a bad time to stand out. They won’t want to call extra attention to themselves by taking medication throughout the school day.”
Twice a day worked best
The UCLA team also tested whether administering the child’s dosage of a protease inhibitor twice a day instead of three times a day produced the same results.
Scientists had never studied this before in children. Krogstad’s team was surprised to learn that the dosage prompted better or the same outcomes in every way.
“The concentration of medication in the child’s blood remained more stable when given twice a day,” Krogstad said. “Because the twice-daily dosage was simpler for kids to take, they followed it more easily — allowing the drug to work more effectively.”
New understanding of drug resistance
Finally, Krogstad’s team explored what happens when a child grows resistant to the multi-drug regimen and the medications stop working.
“We were concerned that a child’s lack of response indicated resistance to all three medications in the regimen,” Krogstad said. “Our research proved this was not the case.”
The researchers discovered that drug resistance developed in a sequence. The first drug to fail was typically the reverse transcriptor inhibitors. The children rarely grew resistant to the powerful protease inhibitors.
“This teaches us that we have more clinical options for treating pediatric HIV,” Krogstad said. “We can combine different drugs with the protease inhibitors to create a regimen that meets the child’s needs.”
The study was funded by the Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. Co-authors included George Johnson of the Medical University of South Carolina, Charleston; Sharon Nachman of the State University of New York at Stony Brook, N.Y.; and Andrew Wiznia of Jacobi Medical Center, Bronx, N.Y.
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