At roughly the same time that treatment was initiated, two tests were conducted to determine whether the infant was infected. Both tests involved PCR on blood samples. PCR detects nucleic acids, the components of both DNA and RNA. Both tests—DNA PCR and RNA PCR—came back positive, indicating that the infant had HIV-infected cells, as well as virus in the blood. Because these tests were positive within the first 48 hours after birth, current guidelines suggest the infant was infected some time prior to birth. Over the ensuing weeks, close monitoring confirmed that the viral load dropped with successive tests, as expected when a patient is responding well to therapy.
Drs. Persaud and Luzuriaga set up a research collaboratory to explore and document possible pediatric HIV cure cases with a grant from amfAR.
Fast-forward over a year, and the mother and child stopped going to the doctor when the child was 18 months of age, returning to medical care at 23 months. At that time, the mother confirmed that her child had not been given antiretroviral therapy for at least five months. The doctors conducted a viral load test to determine an appropriate treatment regimen, and were very surprised when the test came back “undetectable,” meaning there were less than 48 copies of the virus in each milliliter of blood. In a child who has stopped antiretroviral therapy, the result would be expected to be as high as several million. Not trusting the result, Dr. Gay ordered another test, which also came back undetectable. At this point, Dr. Gay contacted her colleague Dr. Luzuriaga at the University of Massachusetts Medical Center for advice. Dr. Luzuriaga, having just established a pediatric HIV cure collaboratory with her colleague Dr. Persaud of Johns Hopkins Children’s Center with funding from amfAR, knew she had the right team of scientists poised to delve more deeply into this case.
These highly sensitive tests collectively suggested that if there was any virus left in this child’s body, it was unlikely to be capable of multiplying and causing disease. Knowing that scientists are skeptical regarding any claims of a cure, Drs. Persaud and Luzuriaga had set up their collaboratory to include scientists specializing in all the tests that had been done to confirm the cure in Timothy Brown. These highly sensitive tests collectively suggested that if there was any virus left in this child’s body, it was unlikely to be capable of multiplying and causing disease.
The French Cohort
Only a week or two after the child cure story broke, French researchers reported they were following 14 people who were “functionally” cured of HIV. These adults had been treated with antiretroviral therapy during acute infection, i.e., within the first several weeks after becoming infected. All had taken antiretroviral therapy for an average of three years and then stopped. They have now been off therapy for an average of more than seven years, and yet their CD4 cell counts are in the normal range and their viral loads are almost all below 50 copies per milliliter of blood, which is the goal for patients who are taking therapy. Although more sensitive laboratory tests have readily detected HIV in these patients, they appear to no longer need to take antiretroviral therapy to maintain their health, hence the designation “functionally cured.”
The French researchers have looked for explanations for these findings both in terms of the virus the patients were infected with, as well as genetic or other characteristics in the patients themselves. So far, there are no clear answers. In fact, the researchers note that only about 10–15 percent of patients who start therapy this early during infection can expect to similarly control their infection after they stop their medications, and so far we have no way of predicting which patients will fall into this category. Some researchers have wondered whether these 14 patients might have controlled their virus even if they had never taken antiretroviral therapy—similar to the small number of people known as “elite controllers”—although the French group has reason to believe this is unlikely.
What Does It All Mean?
What do these three different types of HIV cure tell us? First, there is as yet no cure that can be applied broadly. Timothy Brown’s cure was a grueling and even life-threatening process that cannot be recommended for patients on a wider scale. Moreover, the stem-cell donor in his case had a rare mutation—finding a tissue match for every HIV patient from among these rare gene carriers would be impossible. Mr. Brown’s case has taught researchers which kinds of tests will be needed to satisfy the rightly skeptical scientific community that a cure has taken place.
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