WASHINGTON – AIDS researchers, advocacy organizations and global health officials spent Monday trying to determine whether the report that a baby girl born in Mississippi was cured of the infection is a therapeutic breakthrough or a scientific curiosity.
Even if the report proves true, aggressive HIV treatment starting at birth has no obvious relevance to adults, who are by far the biggest age group infected each year. Even in newborns it may be of little practical use, as nearly all mother-to-child infections can be prevented by a simpler strategy that isn’t yet fully implemented around the world.
At the same time, news of a cured patient — the girl, now 2½, would be only the second on record — has caught the world’s eye. Scientists are confident that even if the case isn’t a signpost to the future, it is of great importance right now. “Just like the first case, it is generating a tremendous amount of attention and, more importantly, a tremendous number of testable hypotheses,” said Steven Deeks, an AIDS researcher at the University of California at San Francisco and a leader of the effort to reinvigorate the search for an AIDS cure.
“I think if that is confirmed, it is one of the greatest pieces of news we can have,” said Michel Sidib, director of UNAIDS. “It can bring us one step closer to the AIDS-free generation.”
Sidib, who spoke from Botswana, said UNAIDS will soon convene a meeting of researchers and global health officials to discuss how and where to test the Mississippi strategy. The most likely sites are in sub-Saharan Africa, where 91 percent of mother-to-child infections occur. “More studies need to be done to understand the outcome,” he said.
UNAIDS’s deputy director for science, Luiz Loures, said designing a clinical trial to test the Mississippi strategy “is not a major challenge.” Implementing it on a large scale is another matter. That would require laboratory equipment that detects the virus, which is not available in many rural settings in the developing world.
About 330,000 babies become infected with HIV each year, either in the womb, during delivery or through breast-feeding. That number has fallen steadily in recent years as countries have implemented a prevention strategy that can cut the mother-to-child rate of transmission from 30 percent to 1 percent. The Mississippi case, described at a scientific meeting in Atlanta, suggests a tool that could reduce the number further. “Is 1 percent an acceptable transmission rate?” asked Deborah Persaud, a pediatrician at Johns Hopkins Children’s Center who was involved in the Mississippi case. “If we have a way to cure the infection in the 1 percent who get it, then that should be our goal.”
She said that “triple-therapy-at-birth” would probably be given only to newborns at unusually high risk of being infected. In most cases that would be those whose mothers were never treated, or became infected late in pregnancy and didn’t know it.
Today, slightly more than 60 percent of pregnant, HIV-infected women in the developing world receive the recommended drugs to prevent transmission of the virus to their babies. Increasing that number is a major priority of many countries and organizations. The Elizabeth Glaser Pediatric AIDS Foundation, for example, tested 1.4 million pregnant women (mostly in Africa) for AIDS in the first nine months of 2012. About 110,000 women received preventive treatment with antiretroviral drugs, as did 85,000 exposed infants.
In the Mississippi case, a woman arrived at a hospital in labor. (The location of the hospital, and personal details have not been revealed). She had had no prenatal care, which would have included an AIDS test. When a screening AIDS test came back positive, it was too late to give the antiretroviral drugs that would normally be given during delivery.
Because of the circumstances, the newborn’s physician, Hannah Gay of the University of Mississippi Medical Center in Jackson, decided to give the girl triple therapy — a three-drug combination of antiretroviral medicines. Usually, the baby would get one drug for six weeks. If testing then showed the baby was uninfected — tests in the weeks after birth are often not definitive — the medicine would be stopped.
Special tests done in the days after the Mississippi infant’s birth showed that she had replicating virus in her bloodstream, which disappeared over three weeks as the triple therapy took effect. Gay and her colleagues are convinced the child was infected. They don’t believe the positive tests simply registered small amounts of virus that had spilled over from the mother’s bloodstream during delivery.
The baby girl, who was born five weeks premature, took triple therapy for about 18 months. Then her mother, who was not on HIV treatment herself, stopped coming to the clinic. When the child was brought back to care at 23 months of age, she had no detectable virus in her bloodstream by conventional measures, even though she hadn’t taken any antiretrovirals for five months.
Since then, traces of HIV genetic material have been detected, but no healthy and replicating virus. Gay, Persaud and Katherine Luzuriaga, a physician at the University of Massachusetts Medical School also involved in the girl’s care, believe she has been cured. Is this a cure in the ordinary sense of the word? That is one of many questions.
The AIDS virus, once in the body, quickly takes up residence in memory T cells, which survive for decades. Eradicating the virus from that “reservoir” has proved impossible except in one documented cure: An HIV-infected American man living in Germany received a bone-marrow transplant for leukemia. The donor’s cells had a rare HIV-resistance genetic mutation, which prevented a return of the infection.
Researcher Deeks said the Mississippi case, even if it stands up to scrutiny, “is not all that relevant to adult infection.”
The reason is because when nearly all adults are diagnosed — either with the flulike symptoms that occur a week after infection, or years later when HIV has damaged the immune system — it’s too late for a cure. By then, Deeks said, “the virus has found itself into these resting memory T cells that are designed to survive for decades.”
The treatment of the Mississippi girl appears to have threaded the needle between bloodstream infection and permanent seeding of the memory T cells. Achieving that in adults, most of whom acquire HIV through sexual contact without knowing it, is exceedingly difficult. But it may not be impossible, Deeks said.
That was suggested by another study presented Monday at the 20th Retrovirus Conference in Atlanta by Thai researcher Jintanat Ananworanich.
Forty-seven men were started on triple therapy within days of infection. After 24 weeks, 11 of them had no detectable virus in memory T cells, suggesting infection in the reservoir had been prevented.