Friday, July 11, 2014

Infant with Early Retroviral Therapy Shows No Signs of HIV

July 11, 2014:

"The child is now nearly 4 and was found to have an HIV RNA level of 16,750 copies per milliliter of plasma, researchers told reporters in the telebriefing. Repeat testing confirmed the finding, as well as showing the HIV-characteristic drop in CD4-positive T cells and the presence of antibodies to the virus. Genetic testing showed the viral strain is the same as the one she originally acquired from her mother.

She has now been re-started on antiretroviral medications and is doing well, her doctors said, with a falling viral load and no adverse effects. To some extent, the glimmer of hope is still there. It is, after all, unprecedented that an HIV-positive child should be off therapy for two years without a viral rebound, noted Deborah Persaud, MD, of Johns Hopkins University in Baltimore."

July 6, 2013:

"I guess the message that I want to get across to the public very strongly is, we don't know yet if we can create the same outcome in other babies. It's far too early to draw too many conclusions. There's not a cure in sight this week," said pediatric HIV specialist Hannah Gay, M.D.
A two-year-old child born with HIV infection and treated with antiretroviral drugs beginning in the first days of life no longer has detectable levels of virus using conventional testing despite not taking HIV medication for 10 months, according to findings presented today at the Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta.

This is the first well-documented case of an HIV-infected child who appears to have been functionally cured of HIV infection — that is, without detectable levels of virus and no signs of disease in the absence of antiretroviral therapy.

Further research is needed to understand whether the experience of the child can be replicated in clinical trials involving other HIV-exposed children, according to the investigators.

The case study was presented at the CROI meeting by Deborah Persaud, M.D., associate professor of infectious diseases at the Johns Hopkins Children’s Center in Baltimore, and Katherine Luzuriaga, M.D., professor of pediatrics and molecular medicine at the University of Massachusetts Medical School in Worcester. These two pediatric HIV experts led the analysis of the case.

"We believe that perhaps the initiation of very early antiretroviral therapy prevented the formation of the viral reservoirs in central memory CD4+ T cells that are the barriers to a cure. And this really sets the stage for the pediatric cure agenda going forward," said Dr. Persaud.

In July 2010, the child was born prematurely in Mississippi at 35 weeks, to an HIV-infected mother who had received neither antiretroviral medication nor prenatal care.

Because of the high risk of exposure to HIV, the infant was started at 30 hours of age on liquid antiretroviral treatment consisting of a combination of three anti-HIV drugs: zidovudine, lamivudine, and nevirapine. The newborn’s HIV infection was confirmed through two blood samples obtained on the second day of life and analyzed through highly sensitive polymerase chain reaction (PCR) testing. PCR tests conducted on separate occasions that indicate the presence of HIV in an exposed infant are considered to have confirmed the diagnosis of infection.

The baby was discharged from the hospital at 1 week of age and placed on liquid antiretroviral therapy consisting of combination zidovudine, lamivudine and co-formulated lopinavir-ritonavir. This drug combination is a standard regimen for treating HIV-infected infants in the United States.

Additional plasma viral load tests performed on blood from the baby over the first three weeks of life again indicated HIV infection. However, by Day 29, the infant’s viral load had fallen to less than 50 copies of HIV per milliliter of blood (copies/mL).

The baby remained on the prescribed antiretroviral treatment regimen until 18 months of age (January 2012), when treatment was discontinued for reasons that are unclear. However, when the child was again seen by medical professionals in the fall of 2012, blood samples revealed undetectable HIV levels (less than 20 copies/mL) and no HIV-specific antibodies. Using ultrasensitive viral RNA and DNA tests, the researchers found extremely low viral levels.

Today, the child continues to thrive without antiretroviral therapy and has no identifiable levels of HIV in the body using standard assays. The child is under the medical care of Hannah Gay, M.D., a pediatric HIV specialist at the University of Mississippi Medical Center in Jackson. Researchers will continue to follow the case.

The only other person considered cured of HIV underwent a very different and risky kind of treatment in 2007. His infection was eradicated through an elaborate treatment for leukemia that involved the destruction of his immune system and a stem cell transplant from a donor with a rare genetic mutation that resists HIV infection. Timothy Ray Brown of San Francisco has not needed HIV medications in the five years since that transplant.

The Mississippi case shows "there may be different cures for different populations of HIV-infected people," said Dr. Rowena Johnston of amFAR, the Foundation for AIDS Research. That group funded Persaud's team to explore possible cases of pediatric cures.

“Despite the fact that research has given us the tools to prevent mother-to-child transmission of HIV, many infants are unfortunately still born infected. With this case, it appears we may have not only a positive outcome for the particular child, but also a promising lead for additional research toward curing other children,” said NIAID Director Anthony S. Fauci, M.D.

About 300,000 children were born with HIV in 2011, mostly in poor countries where only about 60 percent of infected pregnant women get treatment that can keep them from passing the virus to their babies. In the U.S., such births are very rare because HIV testing and treatment long have been part of prenatal care.

More information:
» LA Times: Two HIV-positive men with bone marrow transplant/antiretroviral therapy are negative
» NIH: "Most young women in Africa do not adhere to the daily-use HIV prevention schedule"

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