Therapy hinders AIDS virus from evolving drug resistance, Hopkins researchers find

July 10, 2001

A team of scientists from Johns Hopkins Children's Center and two other institutions have found that low levels of HIV-1 virus in the blood of children and adults undergoing a common combination drug therapy does not necessarily indicate the virus is becoming resistant to these life-prolonging medications.

In the first study to show a low level of viral activity in children using the therapy, called HAART (highly active anti-retroviral therapy), a team led by Children's Center infectious disease researcher Deborah Persaud, M.D., says that bloodstream signatures of HIV-1 revealed no genetic signs that the virus was developing resistance. The finding, published in this week's Journal of the American Medical Association, has implications for the design and future treatment strategies in fighting the onset of AIDS.

"Going into the study, we thought it was possible that even low levels of virus activity could result in the evolution of resistance to HAART drugs," Persaud says. "But both the children and adults in our study showed that the therapy is working."

The report also shows that occasional increases in apparent virus activity, called "blips," do not necessarily indicate the virus is resisting the protease inhibitors and anti-retroviral drugs that make up HAART.

From the blood samples of 20 study participants, all of whom had been on HAART at least 25 months, the research team looked for the unique genetic signature left by very low levels of HIV-1, a virus that inserts itself into the human genome and begins replicating as though it were any other set of human genes.

The researchers compared each viral genetic sequence to other viral sequences from the same patient, to other patients' viral sequences and to sequences that represent drug-resistant viruses. The researchers found that viral replication and mutation had remained suppressed by HAART. Two of the 20 study participants, who responded less than optimally to HAART, were used as controls for spontaneous drug-resistance mutations.

The reason one person can have several, slightly different versions of HIV-1 is that the original infection event itself usually involves the invasion of many non-identical viruses.

The Centers for Disease Control and Prevention estimate that more than 900,000 Americans are infected by either HIV-1, its alternate version HIV-2, or both, about 20,000 of whom are children. While there is no known cure, the onset of AIDS can be significantly delayed in some cases by drug therapies, including HAART. The average life expectancies of people infected with HIV have increased since doctors began prescribing anti-retroviral and protease inhibitor drug therapies.
Researchers from the Johns Hopkins School of Medicine, Harvard Medical School, and the National Institute of Allergy and Infectious Disease also contributed to the report. It was funded by a grants from the Child Health Research Center, the Doris Duke Foundation, the Elizabeth Glaser Pediatric AIDS Foundation and the National Institutes of Health.

"HIV-1 Drug Resistance Profiles in Children and Adults," JAMA vol. 286, no. 2, July 11, 2001.

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