CROI showcases evidence of ‘functional HIV cure’ in child

Much of the recent surge in HIV cure research in the clinical setting has focused on HIV-infected adults. This makes sense, since much of it has been inspired by the celebrated case of Timothy Brown, the so-called “Berlin patient,” who has been free of HIV since he received a stem cell transplant from a donor naturally resistant to HIV. 

But scientists from Johns Hopkins University say they have now identified a toddler who, after receiving antiretroviral therapy in the first 18 months of life, today has no detectable levels of HIV in the blood, or any evidence of disease. The child seems, in other words, to have been functionally cured. 

Details of the case were unveiled by Deborah Persaud, a professor of infectious diseases at Johns Hopkins Children’s Center, at a press conference on Sunday, at the 20th annual Conference on Retroviruses and Opportunistic Infections in Atlanta. Cure research is expected to be one of the dominant themes at the gathering, which runs from March 3-6. “This is only one case, and we definitely need more,” cautioned Persaud. “But we believe this is our Timothy Brown case. This is proof of concept that HIV can be cured in infants.” 

She said the case suggests that delivering ARVs within days of exposure could potentially clear the virus, and induce long-term remission without the need for daily ARVs. Here are the facts of the case as described by Persaud, who will be presenting her findings during a session on Monday. A child born prematurely in 2010 to an HIV-infected mother who had not been receiving antiretroviral therapy was started at 30 hours of life on a liquid regimen of three antiviral drugs—AZT, 3TC and nevaripine—the same day that two separate tests revealed that the child had acquired HIV. 

The baby was discharged from the hospital a week later and put on a liquid regimen of AZT, 3TC and co-formulated lopinavir-ritonavir, which Persaud described as a standard combination 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, a month later the infant’s viral load had fallen to less than 50 copies of HIV per milliliter of blood. 

Persaud declined to say why the child no longer was receiving  ARVs after 18 months and, in any case, Hopkins had not yet been referred the case. But when the child was again seen last fall by specialists at the University of Mississippi, blood samples revealed undetectable HIV levels and no HIV-specific antibodies. Hannah Gay, the pediatrician at the University of Mississippi who had been treating the child, then reached out to Hopkins, which has been at the forefront of HIV cure research. More sensitive tests revealed extremely low viral levels, suggesting that there was some residual virus and ruling out the possibility that the child had developed sterilizing immunity against HIV. 

Persaud acknowledged that there have been other reported cases of what appeared to be transient HIV infection in infants, but she said those cases are murky. One study, published 15 years ago in the journalScience by University of Rochester researchers analyzed 42 cases of suspected transient HIV viremia among 1,562 perinatally exposed, seroconverting infants. It found most of the results had been misinterpreted.  Persaud described 99% of those putative functional cures as “lab mishaps.” The hope, of course, is that the one she has uncovered will not fall into that sad category.