Disappointed federal officials today announced that the “Mississippi baby,” thought to have been cured of HIV with an aggressive treatment regimen, now has detectable levels of virus. The sad news, upsetting for the family of the 46-month-old girl, also dashed the hopes of clinicians who believed a cure for babies born with HIV may be within their grasp.

In a news briefing by the National Institutes of Health clinicians explained that the girl had been off medication for more than two years but had remained seemingly HIV free. Her health had been carefully tracked during regular visits to the clinic every six to eight weeks. But last week testing from a routine examination revealed that the child’s viral load had spiked and that her levels of CD4+ T cells, markers of a normal immune system, had dropped, says Hannah Gay, a University of Mississippi Medical Center pediatrician who treated the patient. The child had been off of her strong HIV drug cocktail treatment for the past 27 months.

Once the new test results were confirmed the child was promptly put on antiretroviral therapy (ART) and there are already clinical indications that the medications are bringing the viral load back in check, her doctors say. The “disappointing clinical result” is a huge blow for the child, her family and the scientific community, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. It feels like a “punch in the gut,” Gay adds. Before last week’s visit there was no sign that the child’s virus was rebounding; prior testing in April had found less than one copy of the virus in her blood.

The child’s mother had not received antiretroviral medication during pregnancy to block transmission of HIV from mother to child. (Most HIV-positive pregnant women in the U.S. do get such treatment now.) Gay had started treating the infant 30 hours after birth with an aggressive three-drug cocktail regimen of antiretrovirals. The treatment was unusually powerful for a child that young and was also started even before tests confirmed she was actually infected. The baby girl was treated for 18 months before the child’s family abruptly halted the drugs. Inexplicably, about 10 months later when doctors examined the child’s blood, they confirmed there was no trace of the virus. The girl, now almost four years old, had apparently kept the virus at bay even without taking medications until now.

Based on this apparent success in Mississippi, researchers had made plans to replicate the treatment among other HIV-positive children in the hopes they could avoid a lifetime of drug therapy. The NIH had imminent plans to launch a new global study that aimed to select 54 HIV-positive infants and treat them with standard antiretroviral drugs starting just hours after birth. Then, if the infants successfully tamped down viral load levels after about two years, drug treatment would be stopped and they would be carefully watched to see if their viral loads rebounded—something that typically happens when HIV positive patients halt their drugs. (Read HIV on Trial: An Attempt to Cure the World’s Smallest Patients) “The study is still in play, but now we’re taking a close look at it,” Fauci says. No patient has yet been enrolled in the trial and researchers will amend the informed consent to include this new finding, he adds. “We are going to take a good hard look at the study and see if it needs any modifications.” If doctors stopped treating patients on their own to see if viral loads remained suppressed, that would be unethical, he notes, but in the context of the clinical trial patients will be carefully monitored.

Currently, there are no guidelines about how HIV positive infants should be treated—whether with an aggressive early drug treatment or with prophylaxis. The study aims to help answer that question.

Unraveling the complexity of the viral reservoir and how the virus managed to persist in the baby will need to be explored, Fauci says. Big questions are triggered by this setback: Where did the virus manage to hide out in the body? Did fragments somehow recombine into a complete, reproducing virus? The recurrence of HIV in the infant will at least silence skeptics in the medical community who questioned if the infant ever had HIV in the first place. “We are still very much in the early discovery phase of trying to achieve a sustained virologic remission and perhaps even a cure,” Fauci says. The “Mississippi baby” is now slated to stay on ART drugs for the foreseeable future, but Fauci adds that in the coming years new research will hopefully change that trajectory.