NIH Trial Tests Very Early Anti-HIV Therapy in HIV-Infected Newborns
A new clinical trial is exploring whether giving anti-HIV therapy soon after birth to infants who became infected with HIV in the womb leads to remission of the virus, enabling the children eventually to stop treatment for an extended time period. The study is sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both part of the National Institutes of Health.
“HIV typically takes just a few days to gain a permanent foothold in a newly infected person,” explained NIAID Director Anthony S. Fauci, M.D. “The theory behind this study is that starting antiretroviral therapy within hours of birth in newborns who became HIV-infected in the womb may limit how entrenched the virus becomes.”
“If this theory is correct, then very early therapy may create conditions that enable the developing immune systems of HIV-infected infants to suppress the virus long term,” said Rohan Hazra, M.D., a medical officer at NICHD.
Adding perspective, Dr. Fauci said, “It is much better to prevent a baby from being born with HIV than to treat a baby who is born infected. The global health community has proven strategies for preventing mother-to-child HIV transmission, but unfortunately, they have not yet been implemented or adopted universally. That is why we must conduct this trial while also striving toward 100-percent prevention of mother-to-child HIV transmission.”
Leading the Phase I/II proof-of-concept study are Yvonne Bryson, M.D., distinguished professor and chief of global pediatric infectious diseases in the David Geffen School of Medicine at the University of California, Los Angeles and Mattel Children’s Hospital UCLA; and Ellen Chadwick, M.D., professor of pediatrics at the Northwestern University Feinberg School of Medicine and the Ann and Robert H. Lurie Children’s Hospital of Chicago.
The trial aims to build on the results of the Mississippi Baby case of an infant born with HIV infection in July 2010 who received triple-drug anti-HIV therapy starting at 30 hours of age—more drugs at higher doses than the norm at that age in the United States. The child fell out of medical care and stopped taking the drugs around 18 months of age, but returned to care 5 months later with no detectable virus in the blood. HIV remained in remission for another 22 months (for a total of 27 months) before it reappeared and the child restarted treatment.
“This case, in which the virus was in remission for an unprecedented length of time for a child who acquired HIV perinatally, represents the first step on a path toward the goal of a lifetime free of therapy for HIV-infected children,” said Dr. Chadwick.
“The intermediate goal that we hope to achieve in the current study is sustained HIV remission in young children to substantially delay the time when they must resume treatment,” added Dr. Bryson.
The study is being conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT), a network jointly funded by NIAID, NICHD and the National Institute of Mental Health at NIH. AbbVie Inc., of North Chicago, Illinois, is donating one of the study medications.
The trial, called IMPAACT P1115, will involve up to 472 babies and their HIV-infected mothers in at least nine countries in Africa and North and South America. With their mothers’ consent, two groups of infants will participate. One group will involve approximately 440 babies at high risk for HIV infection because they were born to HIV-infected women who did not receive any anti-HIV drugs during pregnancy. Within 48 hours of birth, these infants will be enrolled in the study, tested for HIV and started on triple-drug antiretroviral therapy. If it is confirmed that an infant became infected in the womb, he or she will remain in the study; otherwise, the baby will transition to a routine preventive HIV drug regimen and will leave the trial by 4 weeks of age. The study team expects to identify 22 infants in this group who became infected with HIV in the womb.
The second group will comprise up to 32 babies born with HIV infection even though their infected mothers may have taken antiretrovirals during pregnancy. Unlike the first group, these infants will have received their first HIV test and begun receiving antiretroviral therapy outside the trial within 48 hours of birth. They will be enrolled in the study within 10 days of birth if it is documented that they became infected in the womb, and they will continue receiving antiretroviral therapy within the trial.
Study investigators will monitor the health and amount of virus in the blood of all HIV-infected infants.
To learn if giving HIV-infected newborns very early antiretroviral therapy leads to HIV remission, the investigators will, after consultation with the children’s families or legal guardians, stop treatment in those children who are at least 2 years old and in whom the virus has been undetectable for at least 72 weeks. These children will stay off therapy as long as HIV remains undetectable in their blood, and they will be carefully monitored through at least age 5 years and as long as the virus is in remission. The investigators will consider a child’s HIV to be in remission if his or her virus is undetectable for 48 consecutive weeks while off treatment. If the virus reappears in a child’s blood, he or she will restart antiretroviral therapy.
An expert panel will periodically review the state of the science in HIV remission research to determine whether the study’s eligibility criteria for halting treatment are aligned with the latest available data. If necessary, the panel will advise the protocol team to change the criteria. In addition, when a child becomes eligible to stop treatment, study staff will meet with the child’s family or legal guardian to discuss the latest relevant research and work with them to decide whether it is in the child’s best interest to halt treatment.
The study team will separately track babies who are breastfed and those who are formula-fed, as there is a small risk that breastfed babies could acquire a second HIV infection through their mothers’ breast milk, which would complicate interpreting the impact of very early treatment.
The HIV-infected mothers will be cared for by health professionals in the hospitals where they give birth, counseled to start or resume antiretroviral therapy, and linked to physicians in their communities for ongoing medical care for HIV infection.
For more information about the IMPAACT P1115 clinical trial, please see Questions and Answers: The IMPAACT P1115 HIV Clinical Trial or ClinicalTrials.gov under study identifier NCT02140255.
This study is funded by NIH grant numbers UM1-AI-068632, UM1-AI-068616, UM1-AI-106716, UM1-AI-069469, UM1-AI-069436, UM1-AI-069521, UM1-AI-069423, UM1-AI-069477, UM1-AI-069465, UM1-AI-069530, UM1-AI-069421, UM1-AI-069463, UM1-AI-069536, UM1-AI-069518 and UM1-AI-069415, and by contract number HHSN275201300003C.