The child, now four, was born in 2010 to an HIV-infected mother who was untreated during pregnancy.
The baby was given a potent dose of antiretroviral medication 30 hours after birth, and tested positive for HIV.
Doctors allegedly cured the child of HIV by administering the three drugs Epivir, Viramune and zidovudine 30 hours after the baby's birth, according to CNN. The child was then treated with a Kaletra drug combination produced by Abbott Laboratories.
Read: Why are only some babies of HIV+ women infected and others not?
She went off her medication to suppress the human immunodeficiency virus when she was 18 months old, but somehow remained disease-free, showing no detectable level of the virus for more than two years.
Her case raised hopes that doctors may have found a way to cure young children who are born HIV-positive, simply by treating them with drugs early.
"Certainly, this is a disappointing turn of events for this young child, the medical staff involved in the child's care, and the HIV/Aids research community," said Anthony Fauci, director of the National Institute on Allergy and Infectious Diseases in the US.
The girl was tested during a routine clinical care visit earlier this month, and was found to have detectable HIV levels in her blood, as well as a decreased T-cell count and the presence of HIV antibodies.
Read: The 3 ways to test for HIV antibodies
All those factors signalled that HIV was actively replicating again in her body.
She is now being treated once again with antiretroviral medication and is doing well, Fauci said.
"The case of the Mississippi child indicates that early antiretroviral treatment in this HIV-infected infant did not completely eliminate the reservoir of HIV-infected cells that was established upon infection, but may have considerably limited its development and averted the need for antiretroviral medication over a considerable period," said Fauci.
Researchers must now turn their attention to understanding why and how the child went into remission, with the hope of extending that time period even further in future cases.
Scientists find that the pool of inactive HIV viruses that lingers silently in a patient's body is larger than expected
How babies younger than 18 months are tested for HIV
Watch: How HIV positive children are assisted in SA