Potential HIV Cure

Bid to cure HIV ramps up

http://www.nature.com/news/bid-to-cure-hiv-ramps-up-1.13268

HIV–positive mothers who take antiretroviral therapies while pregnant can be prevented from transmitting the virus to their babies 99% of the time — a resounding success story in the decades–long fight against the virus. But what about infants whose mothers do not receive the drugs? Energized by the case of the ‘Mississippi baby’ — who seemed to be cured of HIV after aggressive treatment was begun within hours of birth — researchers are hoping to show that these infants, too, can get off to a healthy start.

At a symposium on HIV cure research on 29 June at the International AIDS Society’s biennial meeting in Kuala Lumpur, Malaysia, investigators will describe how they are racing to design a clinical trial to test whether the early treatment works, and why. They hope to treat the first babies by the end of this year. The trial, sponsored by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, marks a change for the field: so far, most research worldwide has focused on adults. In 2012, the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, spent US$18 million on HIV cure research in adults and adolescents, and just $45,000 on children. Yet 3.3 million children worldwide have HIV.

“Children have been an afterthought,” says Jeffrey Safrit, director of clinical and basic research for the Elizabeth Glaser Pediatric AIDS Foundation, who is based in Los Angeles, California. “But the immune system of the child might be more easily manipulated to allow a cure.” This was highlighted in March, when virologist Deborah Persaud of the Johns Hopkins Children’s Center in Baltimore, Maryland, announced that a baby in Mississippi who received treatment for HIV within 31 hours of birth stopped medication at 18 months without the virus rebounding. Researchers knew that early treatment could help infants to control HIV, but were surprised that they could essentially wipe it out from an infant’s body using existing drugs.

This is fantastic news in the fight against AIDS. As we are reminded above, it was greatly heartening to see the first infant cured from HIV earlier this year. Now physicians are looking to take this breakthrough to the next level. There is a likelihood that babies and potentially children would be easier to cure than adults. This is due to their immature immune systems which respond more mildly when provoked – ‘Because the cells involved in this ‘inflammatory response’ are the same ones that are most susceptible to HIV, this could mean that infants are less prone to the infection spreading’. Also babies are born without central memory T cells (the main immune centre where HIV hides from drugs), so babies are likely to have a smaller area of infected cells. All of the babies in the study will be screened and given a cocktail of three drugs within 48 hours of birth as diagnosing HIV takes up to 7 days. If the infant then tests positive for HIV a fourth drug will be administered.

At around three years old the children will be tested to see If their immune systems make antibodies to HIV or whether it can be detected in their blood. If both counts are negative then they will be taken off the drugs to see if they can remain HIV–free. The study looks to be sound and evidently for an excellent cause but there are problems. The babies of untreated HIV infected women have only a 15–30 percent chance of infection at birth, so unfortunately, the trial would need to recruit as many babies as possible to cure the few who are infected. This sounds controversial, but the side effects do not appear to be severe – depleting certain blood cells. The general consensus is that the risks are far outweighed by the potential for finding a cure: ‘The potential for finding a cure far outweighs the risks of adding another drug, or of stopping treatment to test whether the cure has worked’ says Yvonne Bryson (a physician at the Mattel Children’s Hospital, University of California).

This study could have far reaching effects, physicians are already thinking about changing the way they treat children affected by HIV. For adults infected too there is pause for thought. If infants are more receptive to cures because they have a less active inflammatory response then it may encourage physicians to prescribe treatments that are less likely to trigger inflammation in adults.

What is most exciting is that we could be on the brink of curing this terrible disease – “I saw patient zero,” Bryson says. “I’ve always been so excited to think that I would see the day that we would arrive at a cure, and I think we’re here.”

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