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Expert Commentary from Luis Montaner: A baby "functionally cured" of HIV
wistar

Since my return from the 2013 Conference on Retroviruses and Opportunistic Infections last week, I’ve been asked repeatedly about what is undoubtedly the biggest news of the meeting: “So, do you think she is cured?”

Referring, of course, to the baby who was deemed cured of HIV infection. According to a report from University of Mississippi researchers, a child given antiretroviral therapy (ART) soon after birth is now described as “functionally cured.” 

Allow me to answer some of the questions I have received thus far.

Although no one knows for sure, we do know that very early treatment with full doses of three drugs on this newborn—which is not the current standard of care—achieved an unexpected level of control for viral replication, or potentially a cure, once treatment was halted. There are unique aspects to this child’s therapy history, specifically starting treatment within 48 hours of birth, starting full doses of three drugs and stopping all therapy at 15 months of age. All three of these things are not common practice in the majority of newborns from HIV-infected mothers.

So what is the normal time frame for initiating treatment in newborns? The guidelines are not very specific other than confirming infection over time before starting therapy with at least two tests.  In this case, the two tests where done hours apart in the first two days which is not usual.  The July 2012 guidelines offer detailed information on page H-19, to quote: "Virologic tests are required to diagnose HIV infection in infants <18 months of age and should be performed within the first 14 to 21 days of life, at 1 to 2 months, and at 4 to 6 months of age.” 

So, performing two tests that meet “criteria” for infection just hours apart after birth is not specifically indicated by current guidelines.  Does this case call for changing the guidelines in the future?

If you take the fact that the child would have been expected to be on therapy for life, an absence of replicating HIV after 15 months of therapy is remarkable on its own. If this can be replicated in other newborns, it may indeed change the way we handle testing and treatment of newborns from HIV-infected mothers.

Interestingly, a French report from 2012 had already described that early treatment in adults can result in about one in 10 patients becoming "controllers” (persons with a low level of viral replication after stopping treatment), that is, able to manage their infection after going off ART. 

There might be a pattern here. It could very well mean that the baby is part of that approximately 10 percent of people found among adults in the French study. Or maybe this effect occurs more potently in newborns, or at a higher percentage. 

Another idea arises: what if the baby is a long-term “non-progressor” (that is, the disease does not advance) or a controller, as opposed to cured? While possible, it is of interest to note that in contrast to this case, such elite controllers show: (a) lower viral loads without treatment (about 20,000 in this baby, although you can find higher viral loads in general among children); (b) there is residual HIV detected on or off treatment between 0-50 copies per microliter (none detected in a toddler after stopping therapy), and (c) evidence of immune responses as persisting without treatment (none detected to persist in this case).

So, is she cured? Note the team refers to this as a "functional" cure as they can still detect traces of HIV even if they cannot tell if those traces of HIV are capable of replicating…or are just leftovers that mean nothing. After the presentation, discussions among attendees argued against the term "functional," as there was no immune response detected to support any "function" in maintaining control. The answer from the presenters was in line with: "We do not know what to call it, so functional cure seems the conservative route to take in case it comes back..."

Lastly, was the baby actually infected at birth, or just "at risk” with transient virus without an actual infection?  The baby had two independent positive tests for HIV load (although tested twice within 48 hours), had a detectable viral load around 20,000 versus her mother, who was at about 6,000.  After ART, and tests reveal the child’s viral activity showed a decay pattern as in adults. So the child was at risk and the only evidence that she was infected before therapy was the two early tests for HIV nucleic acids. While it is still possible (although highly unlikely) that the child was not infected, the news will drive other researchers to replicate this in other patients, which is what matters in the end.

Will we know if this case fits a cure outcome? Yes!

We will learn what happens to her over time. We will also learn if others can achieve the same outcome. Regardless of the answer as of this day, it was a great leap forward. 

So the question is not “Is she cured?” but, “How soon until we learn if others can follow the same outcome?” The answer is: soon.

Luis J. Montaner, D.V.M., D.Phil. is Professor and Director, HIV-1 Immunopathogenesis Laboratory at The Wistar Institute. Read about the HIV research in the Montaner Lab here.