A Mississippi baby reportedly cured of HIV could prove to be a starting ground for eliminating pediatric HIV and AIDS. But the road to a cure for pediatric AIDS is hardly a smooth one -- even if the Mississippi case turns out to be more than a fluke, getting to a cure likely means years of studies and clinical trials, and finding the money to get more medicines to children at risk.
On Sunday, Researchers from Johns Hopkins Children’s Center, the University of Massachusetts Medical School and the University of Mississippi Medical Center announced they had found a case of a “functionally cured” HIV-infected infant. The child started antiretroviral therapy within 30 hours of birth, and, by 29 days after birth, the virus was undetectable.
When the child was about 18 months old, the mother started missing appointments, and the child fell off the treatment schedule. But at a follow-up examination, when the child was 28 months old, blood tests showed no sign of the virus.
“Our next step is to find out if this is a highly unusual response to very early antiretroviral therapy or something we can actually replicate in other high-risk newborns,” Johns Hopkins virologist Deborah Persaud said in a statement.
Infants at high risk for HIV infection already receive antivirals at birth but typically do not switch to therapeutic-level doses until they are six weeks old. The findings from Perdaud and her colleagues could make the case for intensifying treatment earlier on.
But more studies will need to be done to prove the principle that therapeutic levels of anti-HIV drugs so soon after birth can render the virus undetectable.
“It’s a hypothesis-generating case,” National Institute of Allergy and Infectious Diseases head Anthony S. Fauci told the Washington Post. “It will give us some food for thought about studies that need to be done to see if this is a real phenomenon.”
HIV lingers inside a person for life by maintaining “reservoirs” of its genetic code in infected cells. These cells are not targeted by anti-HIV drugs and allow the virus to lie safe and dormant for years. But attacking the virus very early on, before it has a chance to develop these reservoirs, could smoke HIV out of the body before it gets the chance to hide.
This kind of potential cure wouldn’t be much help to older patients where the virus already has a firm foothold. Despite advances in treatment that allow patients to live a relatively normal life -- basketball player Magic Johnson announced his infection more than 21 years ago and is still relatively robust -- a cure remains elusive. A man named Timothy Brown, also known as “the Berlin patient,” appeared to be cured of HIV after a bone marrow transplant from a donor with a rare genetic mutation that blocks HIV from entering cells, but such a procedure is likely not feasible for the majority of HIV patients.
As with any drug, there are risks to consider when giving anti-HIV drugs to children. The most common side effects associated with antiretroviral therapy are diarrhea, headache and nausea. Certain drugs can be more dangerous than others. Some children have a gene variant that makes them hypersensitive to a drug called abacavir. And earlier treatment also raises the risk that the virus inside the child develops resistance to the drugs.
Because of the potential widespread benefits, the researchers have been toying with the idea of early, intense antiviral therapy for years.
“The notions of ‘test and treat’ and ‘treatment as prevention’ come as no surprise to anyone who has been involved in the fields of prevention of mother-to-child transmission of HIV and pediatric HIV care,” Harvard University researcher Marc Lallemant wrote in a 2011 article for the New England Journal of Medicine.
In his article, Lallemant pointed out that mother-to-child transmission of HIV is extremely low in wealthy countries. But HIV-exposed children in poor countries often have to wait to be tested until they’re 15 to 18 months old -- too late for the kind of intervention that helped the Mississippi child and often too late to save a child from dying.
A South African trial called CHER, which looked at the effectiveness of early treatment in 377 HIV-infected children, wrapped up in March 2012. In that study, researchers found that infants that started antiretroviral therapy right away and continued for one or two years had better survival rates than those who did not start treatment until their disease worsened, which is the current standard of care.
“Early treatment followed by a break may become an accepted strategy in the future,” CHER principal investigator Mark Cotton, of Stellenbosch University, said in a statement last March. “It is definitely better and more cost-effective than delaying starting infants on treatment.”
But there’s a lack of HIV drugs formulated specially for children. Some HIV drugs interact badly with tuberculosis medication, which is another big concern in low-income countries. And, of course, there is the cost. Many researchers like Lallemant see pediatric HIV, a largely third-world problem, as a neglected disease.
“Since HIV was first discovered, more than 20 antiretroviral drugs and several additional antiretroviral combinations have been approved for the treatment of HIV, and today there remains a robust pipeline of new products in development,” Lallemant wrote in NEJM. “Yet there is no such pipeline for pediatric HIV. Because it has been virtually eliminated in wealthy countries, pharmaceutical companies have little incentive to develop child-appropriate formulations.”