IT MIGHT BE AND MIGHT NOT BE HIV CURE

Researchers are calling the apparent disappearance of HIV in a baby born with the infection a ‘functional cure,’ and the media is hailing the news. Dr. Kent Sepkowitz on why they should tread more softly.

This week at the 20th annual Conference on Retroviruses and Opportunistic Infections in Atlanta, a group of researchers announced they had achieved a “functional cure” of a newborn baby with HIV infection. The news made a major splash and raised hopes that a giant step forward in controlling this devastating infection was finally at hand.

Pediatric HIV expert Deborah Persaud, M.D., a virologist at Johns Hopkins University in Baltimore, who presented the findings at the Conference on Retroviruses and Opportunistic Infections in Atlanta. (Johns Hopkins Children's Center)

To which I say—maybe. But probably not. The story is this: a pregnant woman with no prenatal care appeared in premature labor at a small rural hospital. She was not known previously to be HIV infected but on testing was found to have antibody to the virus. At this point, the infant was transferred to a larger hospital and tested for HIV itself and not for antibodies that might simply reflect the mother’s bloodstream. This test was repeatedly positive in the infant, though at surprisingly low levels,
suggesting a relatively small amount of virus circulating in the infant.

The implications of the low level of virus are uncertain, but any detectable virus is considered incontrovertible evidence of infection. Therefore, seeing this result, the treatment team initiated a potent treatment—not preventive—regimen of antiretrovirals for the infant. The child’s virus became undetectable after about a month, a standard response for anyone initiating treatment.

Then the story takes a strange turn. Just as the mother’s poor connection to medical care resulted in a precipitous delivery without prenatal attention, so too did her decision not to follow up with her and her child’s doctors lead to the exciting finding. She and her baby quit showing up after 18 months, then eventually resurfaced months later. Once they had returned, the infant was retested and, to everyone’s surprise, had an undetectable amount of virus in its bloodstream despite no treatment for many months. In every other reported case, people with HIV infection who stop their medications “rebound” within days to a viral load in the bloodstream similar to that of their level before they initiated treatment. So the infant’s absence of detectable virus was an extremely unusual and seemingly unprecedented response. And just maybe a cure.

Amid all the excitement, debate continues on two fronts. First, was the child truly infected? The low viral load was a very unusual but not unheard-of finding, meaning we may never know the truth. Second, does the current spate of normal tests truly indicate a cure? With ultrasensitive testing, the child does have some evidence of scraps of HIV in its bloodstream, not enough to duplicate and then spread but still something that remains present, at least in shadow form. That’s not nothing. And 10 years of stability is but a moment of time for HIV, for which progression is measured in years. Therefore, “cure” or even “functional cure” seems a reach. A stable suppression in the absence of ongoing therapy would be a more accurate description—and one that likely would have been used in a less dramatic and headline-grabbing disease.

Experts should step back and think carefully about how to present data from a small case report of uncertain biologic significance.

But even if the child is indeed cured, as everyone hopes, the treatment approach presented is not relevant to the 34 million people now infected, as the hallmark of the new finding is treatment almost immediately after infection. Most of the world has well-established infection with HIV genes spliced into their own DNA. Nor will it work for uninfected persons who are exposed sexually. For them, an analogous program of mandated testing is not in place, and to test everyone within 24–48 hours after every sexual exposure to mimic the conditions of postpartum screening is wildly unrealistic.

That said, the new information may have a profound public health impact if the paradigm holds up and can be brought to some or most of the 330,000 infants born annually with HIV worldwide, including the 200 or so in the United States. Operationalizing this approach will be a challenge. Key questions include how to get to infants, many of whom are born at home or else far from high-tech medicine, how to monitor them while they take the potentially toxic antiretrovirals, and when to stop the medication to see if “it worked.” These are exciting research questions that solid science will sort out in the years ahead.

The real story, though, is not whether the child was cured. Instead it’s the way the mother presented—as an undiagnosed pregnant woman without prenatal care in a rural area unequipped to manage HIV. In the U.S. in 2013, we have the tools to have prevented transmission to the infant. The use of AZT was shown almost 20 years ago to reduce the risk by 66 percent, and more potent regimens have reduced it even further. But the drug cannot be offered unless a mother’s HIV status is known. Once again, a basic, cheap, easy public-health approach has failed because our health-care system, safety net and all, did not find a way to support the health of a pregnant woman.

Plus, there is a cautionary tale here for the world of HIV. Although it feels like the disease has been here forever, HIV is new and still settling into a set of expectations. In the cancer world, the term “cure” is used all of the time, but when we read it, we know what it means—a small step forward somewhere. And indeed cancer treatment has muscled forward slowly, steadily, relentlessly, even heartlessly at times over the past 60 years, with the occasional dramatic lunge into something new and truly thrilling.

For HIV, though, real therapy began only 18 years ago with the introduction of a class of drugs, the protease inhibitors. These medications transformed the disease within a few years from a predictably fatal infection to a chronic disease but never really promised a cure. Control, yes—but no escape from the tedium of daily treatment. As a result, the term “cure,” with its dizzying narcotic of animal hope and runaway dreams, has not often been placed into the HIV discourse. Now that it has, experts should step back and think carefully about how to present data from a small case report of uncertain biologic significance. Until the word “cure” finds a more realistic context in the world of HIV, those who present and those who report should perhaps tread more softly in their claims—because they tread on countless people’s dreams. And those dreams will not come true from the findings from this latest report.