March 4, 2013
First-Ever HIV Cure Found For Mississippi Baby
Lawrence LeBlond for redOrbit.com - Your Universe Online
AIDS research has come a long way since the disease was first clinically discovered in 1981 and officially named by the US Centers for Disease Control and Prevention (CDC) in 1982. And although many hurdles had been overcome in the prevention and treatment of the world´s deadliest sexually-transmitted infection (STI) over the past thirty years, no real cure had ever been found.
Unveiling their landmark findings at the 2013 Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta, Georgia, Dr. Deborah Persaud of Johns Hopkins University (JHU) and colleagues described the first documented case of a child being cured of HIV, the viral infection that causes AIDS.
Dr. Persaud said at the conference that the two-year-old child was diagnosed with HIV at birth and was immediately administered antiretroviral therapy (ART). But at 18 months, the child stopped receiving the antiretrovirals and had gone without follow-up for five months. When the team was able to reestablish contact at 23 months of age, doctors ordered a battery of highly sensitive tests on the child. Through these tests, the doctors confirmed that there was an absence of HIV.
The follow-up was made possible by a grant given to Dr. Persaud and her colleague Dr. Katherine Luzuriaga of the University of Massachusetts in September 2012. The grant allowed the doctors to establish a research collaboratory and to explore and document possible pediatric HIV cure causes. This collaboration included Drs. Stephen Spector and Doug Richman of the University of California, San Diego (UCSD); Dr. Frank Maldarelli of the National Cancer Institute (NCI); and Dr. Tae-Wook Chun of the National Institute of Allergy and Infectious Diseases (NIAID).
Another doctor, HIV specialist Hannah Gay, MD, associate professor of pediatrics at the University of Mississippi Medical Center (UMC) provided treatment to the child.
"The child's pediatrician in Mississippi was aware of the work we were doing, and quickly notified our team as soon as this young patient's case came to her attention," said Dr. Rowena Johnston, American Foundation for AIDS Research (amfAR) vice president and director of research. "Because the collaboratory was already in place, the researchers were able to mobilize immediately and perform the tests necessary to determine if this was in fact a case of a child being cured."
Upon further investigation, Dr. Persaud and her colleagues were able to confirm beyond doubt that both the mother and the child were HIV positive when the child was born, and after employing the most highly sensitive means available, the research team further confirmed that the child today has no signs of HIV infection.
The researchers said the child went into remission after receiving the ART within 30 hours of birth. They said the prompt administration of the treatment likely led to the infant´s cure by halting the formation of hard-to-treat viral reservoirs — dormant cells responsible for reawakening the infection in HIV patients within weeks if therapy is stopped.
Dr. Persaud said this case may open up new avenues for the treatment and potential cure of HIV in other children. "Prompt antiviral therapy in newborns that begins within days of exposure may help infants clear the virus and achieve long-term remission without lifelong treatment by preventing such viral hideouts from forming in the first place," Persaud said at the conference.
The team of researchers believes this is exactly what happened in this case. They said the infant is now “functionally cured,” which means the patient achieves and maintains long-term viral remission without lifelong treatment and without further detection of HIV in the bloodstream.
A functional cure is in sharp contrast to a sterilizing cure, which translates to the complete eradication of all viral traces from the body. Functional cures occur when the viral presence is so minimal, that it remains undetectable with standard clinical tests, yet can be detected through other highly-sensitive methods.
The researchers said that even ten months after discontinuation of treatment, no HIV was present in the blood. And tests given for other HIV-specific antibodies also remained negative.
The team said natural viral suppression without treatment is rarely observed in the adult HIV community, and less than one percent of HIV-infected adults whose immune systems are able to rein in viral replication can keep the virus at clinically undetectable levels; these individuals are known as “elite-controllers.” Researchers have long been searching for a way to help all HIV patients achieve this elite-controller status, and this new case may lead them down the right path as it suggests prompt ART in newborns can do just that.
THE BERLIN PATIENT
While this is being hailed as a landmark case, it isn´t the first case of a person being cured of the infectious disease.
The only other documented case of an HIV cure comes from Germany. Timothy Brown, dubbed the “Berlin patient,” was receiving HIV treatment in 2006 when he was diagnosed with leukemia. His physician treated the cancer with a stem-cell transplant from a person who was born with a genetic mutation causing immunity to HIV infection. Following the transplant, Brown was able to stop HIV treatments without experiencing a return of HIV infection.
That case, along with the new one, suggests that different populations of people infected with HIV may just be cured in different ways. While Brown´s case was the result of a complex and highly expensive series of procedures, the new one appears to have been a direct result of relatively inexpensive ART methods.
"Given that this cure appears to have been achieved by antiretroviral therapy alone," said Dr. Johnston, "it is also imperative that we learn more about a newborn's immune system, how it differs from an adult's, and what factors made it possible for the child to be cured."
This case also highlights the importance of identifying HIV infection in pregnant women, expanding access to treatment regimens that can prevent mother-to-child transmission, and immediately putting infants who are HIV positive at birth on ART immediately.
While this was a significantly remarkable case, the researchers said there is still not enough data to recommend change to the current practice; but it does provide enough evidence to start proof-of-principle studies in all high-risk newborns.
"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," said Persaud, who is also the scientific chair of the HIV Cure Committee of the International Maternal, Pediatric Adolescent AIDS Clinical (IMPAACT) network, a consortium of researchers and institutions that was critical in spearheading the earliest clinical trials of mother-to-child transmission and early treatment of infants 15 years ago.
Dr. Luzuriaga, who worked closely with Gay, said the developments were fascinating.
"This is the very first case in which we've conclusively been able to document that the baby was infected and then after a period of treatment has been able to go off treatment without viral rebound," Dr. Luzuriaga told CNN's Saundra Young.
Even though no specific test was given to the baby to confirm the child was HIV positive, doctors know that HIV-positive mothers always pass on the antibodies to their babies.
"One hundred percent of (HIV-positive) moms will pass those antibodies, but in the absence of treatment, only [30 percent] of moms will transmit the actual virus," Luzuriaga said.
HIV-positive mothers given the appropriate treatment pass the actual virus on in less than 2 percent of the cases she noted.
"So all babies are born antibody positive, but only a fraction of babies born to HIV positive women will actually get the virus, and that fraction depends on whether the mom and baby are getting antiviral prophylaxis (preventative treatment) or not," said Luzuriaga.
Dr. Persaud said that standard ART — a combination of at least three drugs used to suppress HIV and stop progression of AIDS — does not kill the virus. However, in the Mississippi newborn´s case, the early treatment of ART seems to have killed the antibodies that can lead to the virus, essentially leading to a “functional cure.”
The researchers cautioned that this only represents one case, involving just one patient, and the findings appear to have little immediate relevance to adults or adolescents who contract HIV and who are almost always diagnosed with HIV/AIDS sometimes years after an initial infection.
But if the further research can confirm that very early treatment can cure the disease in newborns, it could lead to widespread use of an aggressive regimen in newborns born with HIV, with the largest percentage of such cases occurring in low- to middle-income countries.
According to data from the World Health Organization (WHO), the odds of infected pregnant women transmitting the virus to their babies during gestation, birth or breastfeeding ranges from 15 to 45 percent. The group estimates that between 300,000 and 400,000 infants are born worldwide each year with the infection, about 90 percent of them in resource-poor countries in sub-Saharan Africa.
In the US, HIV-positive newborns are now rare thanks to tougher standards in prenatal care and routine HIV testing during pregnancy. HIV-positive newborns reached a peak of 1,650 cases in 1991, dropping to fewer than 200 per year today, according to the CDC.
In the case of the Mississippi child, Gay contacted her longtime friend and colleague Dr. Luzuriaga, who had been working with Dr. Persaud on a study group of teenagers who had been born with the virus and treated since infancy and who now had no evidence of the virus that could replicate.
With a collaboratory that Luzuriaga and Persaud had already set up to study whether they could consider taking the teens off the drugs, they received a grant from the National Institutes of Health (NIH) and amfAR to further study samples from the baby and set up a series of highly-sensitive tests to detect and monitor HIV/AIDS.
"We are proud to have played a leading role in bringing this first pediatric HIV cure to light," said amfAR CEO Kevin Robert Frost. "The case is a startling reminder that a cure for HIV could come in ways we never anticipated, and we hope this is the first of many children cured of HIV in the months and years to come."
As for Brown, who was cured of his HIV in 2007, he said in a recent interview with CNN chief medical correspondent Dr. Sanjay Gupta, that he was still HIV-free.
"I've been tested everywhere possible," said Brown. "My blood's been tested by many, many agencies, I've had two colonoscopies to test to see if they could find HIV in my colon, and they haven't been able to find any."