Lawrence LeBlond for redOrbit.com – Your Universe Online
An HIV case first documented in a Mississippi baby 18 months ago is still proving that an antiviral treatment early on is effective in not only treating the virus that causes AIDS, but also curing it.
Earlier this year, researchers from Johns Hopkins University (JHU) reported that a child born with HIV and treated with a series of antiviral drugs showed signs of remission within days of initial treatment. The child was administered antiretroviral therapy (ART) for the next 18 months before ultimately being taken off the drugs.
The researchers, led by Deborah Persaud, MD, of JHU, conducted a follow-up in late 2012 when the child was 23 months of age and found that, after conducting a battery of tests, the infant was in full remission with no visible signs of HIV in the body. They presented their findings at the 2013 Conference on Retroviruses and Opportunistic Infections in Atlanta, Georgia.
REMISSION CONTINUES
Now, more than 6 months later, the same researchers have conducted another follow-up and are happy to report that the child, now 3 years old, is still free of active infection 18 months after all treatment ceased. A new report on the case has been published in the Oct. 23 issue of the New England Journal of Medicine (NEJM).
“Our findings suggest that this child’s remission is not a mere fluke but the likely result of aggressive and very early therapy that may have prevented the virus from taking a hold in the child’s immune cells,” says Dr. Persaud, a virologist and pediatric HIV expert at Johns Hopkins Children’s Center (JHCC), who has been handling the case since the child was born.
Persaud has worked on this case with immunologist Katherine Luzuriaga, MD, of the University of Massachusetts Medical School, and pediatrician Hannah Gay, MD, of the University of Mississippi Medical Center, who identified and treated the baby and continues to see the child.
“We’re thrilled that the child remains off medication and has no detectable virus replicating,” Gay says. “We’ve continued to follow the child, obviously, and she continues to do very well. There is no sign of the return of HIV, and we will continue to follow her for the long term.”
The child was born to an HIV-infected mother and was administered ART within 30 hours of birth. A series of tests in the subsequent days and weeks showed the ART was continuing to diminish the overall presence of the virus in the child’s blood, until it reached undetectable levels 29 days after birth. At 18 months of age, the child was lost to follow-up for nearly five months, and ART stopped; but when checked after another five months, testing could still not detect virus in the bloodstream.
Persaud and colleagues say this one child’s experience provides “compelling evidence” that infants infected with HIV can achieve remission when ART begins within hours or days of birth or whenever infection begins. Based on the information from this case, a federally-funded study is set to begin in 2014 to test early-treatment ART to determine whether the approach is feasible for all HIV-infected newborns.
Persaud and colleagues maintain that swift intervention likely led to the child’s remission because it halted the formation of hard-to-treat viral reservoirs – dormant HIV hiding in immune cells that can reignite in patients within weeks of halting drug therapy.
“Prompt antiviral therapy in newborns that begins within hours or days of exposure may help infants clear the virus and achieve long-term remission without the need for lifelong treatment by preventing such viral hideouts from forming in the first place,” Persaud says.
BERLIN PATIENT
As previously reported by redOrbit, as well as other media sources, this is not the first case of remission of HIV in a person.
Timothy Brown, widely known as the “Berlin patient,” is the only other known person to be effectively cured of HIV. However, unlike with the Mississippi child, who was administered 18 months of ART, Brown was cured through a different means altogether.
In 2006, while receiving treatments for his HIV infection, Brown was diagnosed with leukemia. His cancer was subsequently treated with a stem-cell transplant from a person who was born with a genetic mutation causing immunity to HIV infection. Following that transplant, Brown was able to halt all HIV treatments without experiencing a return of HIV infection.
However, Brown’s case was unique and it is unlikely such procedures would be feasible for the general public of HIV patients due to the cost of such treatments. Also, a stem-cell transplant is typically viewed as necessary in a cancer scenario where often times the only other possible outcome is death, whereas HIV can usually be treated through antiviral therapy, allowing patients to lead otherwise normal lives.
In the Mississippi child, continuing tests for HIV-specific antibodies remain negative to date, as do tests to detect the presence of cytotoxic (killer) cells that the body deploys to destroy viral invaders and whose presence indicates active infection. Highly sensitive tests designed to hunt down trace amounts of the virus have detected intermittent viral footprints in the child’s system, says Persaud. However, these footprints appear incapable of forming new viral infections.
Furthermore, the child also exhibits none of the immune characteristics seen in the so-called “elite controllers,” a tiny percentage of HIV-infected people whose immune systems allow them to naturally keep the virus in check without treatment. Such people have immune systems that are revved up to suppress viral replication. So it is clear that early ART, rather than natural immune mechanisms, led to the child’s remission, the authors report.
PREEMPTIVE MEASURES
Currently, newborns who have a high-risk of HIV infection, either due to poorly controlled infections seen in the mother or in mothers who are diagnosed with HIV at time of delivery, are administered a preemptive combination of antivirals to prevent an infection. ART treatment does not start until an actual infection is confirmed. While a prophylactic approach is significant in preventing at-risk infants from acquiring HIV, it does nothing for those who are already infected with the virus. These infants would likely stand to benefit highly from prompt ART, as did the Mississippi baby.
“This case highlights the potential of prompt therapy to lead to long-term remission in those already infected by blocking the formation of the very viral reservoirs responsible for rekindling infection once treatment ceases,” says Luzuriaga, senior author of the NEJM report. “This may be particularly true in infants, whose developing immune systems may be less amenable to the formation of long-lived virus-infected immune cells.”
“Indeed, recent studies in HIV-infected infants have shown a marked reduction in the numbers of circulating virus-infected cells when babies are treated during the first few weeks of infection. Research has also shown that many hard-to-eradicate viral reservoirs begin to form very early, within weeks of infection. Taken together, these findings mean that the window of opportunity to achieve remission may close very quickly,” according to a JHCC statement.
Persaud and her colleagues maintain that despite the significance of treating HIV-infected newborns early on, preventing mother-to-child transmission remains the primary public health goal. The report authors caution that the approach is still considered preliminary and more research is needed to confirm the efficacy of such treatments. Also, they advise that children with confirmed HIV infection should not be taken off antiviral treatment.
According to background information in the study, nearly 3.3 million children around the world live with HIV infection. More than 260,000 acquire the virus from their mothers during delivery despite advances in preventing mother-to-child infection.
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