December 8, 2013
The "baby cure" has been hyped and is sensational as a news story. But what may have happened to this child is a sensation and has spawned debates on defining infection with HIV, how eradication of the virus can be proved, and the nature of a health care system in which a mother and her child can so easily slip from medical care.
The dramatic story is well known. A woman in Mississippi presented in labor at 35 weeks gestation. She had no pre-natal care. A rapid HIV test performed during labor found the mother to be HIV seropositive. A viral load drawn the next day was 2,400 copies/mL and a CD4+ cell count taken two weeks later was 644 cells/mm3. The baby was delivered prior to the administration of antiretroviral therapy to the mother. At 30 hours after delivery, the infant received zidovudine, lamivudine and nevirapine (Viramune). At antiretroviral therapy initiation, HIV-1 DNA was detected in the baby's PBMCs (peripheral blood mononuclear cells) and an HIV-RNA level of 19,000 copies/mL was found in her blood plasma. Antiretroviral therapy was modified with lopinavir/ritonavir replacing nevirapine at day 11 following delivery. Over the next few weeks, the infant's HIV-RNA level fell and was undetectable at 29 days. Then, 18 months after delivery, mother and baby vanished. Five months later, both return to clinic and the mother reports not administering antiretroviral therapy to her child over the period they were out of care. Testing of the child, however, reveals no detectable viral DNA or RNA and HIV antibodies are not detected. Follow-up testing up to 36 months of age of the child fails to reliably detect evidence that she is infected.
When first reported at CROI 2013, there was debate as to whether the infant was truly ever infected or instead had maternal virus that was transiently circulating shortly after delivery. The authors of the case report published in the New England Journal of Medicine argue that the persistent detection of HIV RNA in the plasma and the dynamics of the decay of viremia in the baby following antiretroviral therapy indicate infection did occur. They also debunk the theory that passive maternal transfer without active replication could account for prolonged detection of virus in the quantities measured in the infant.
Despite the important and necessary debate regarding what actually happened within the small body of this child in Mississippi, the case report has focused attention on the potential opportunity to avert or even cure HIV infection during delivery. Practically, many are being more aggressive with antiretroviral therapy in babies born to mothers with uncontrolled HIV and studies of such an approach are being launched in the developing world.
The case also has led to the examination of what could account for a cure under the circumstances described. The immaturity of an infant's immune system and a lack of central memory T cells may hinder propagation of the virus and produce a smaller reservoir of virus. As HIV cure efforts continue to ramp up, this case may offer tantalizing clues that can be useful not only for addressing perinatal transmission, but also eradication in older individuals.
While this case of a potential HIV cure may be incredibly special, in another way, the story is all too familiar. The falling out of care of the mother and child is emblematic of a health care system that, for all its costs, fails to deliver to many of those most in need. The details of how the pair became "lost" are not known, but may be important to illustrate the challenges people face in accessing and utilizing health care in our country.
In the HIV cascade describing engagement in care of those living with HIV, the greatest drop along the spectrum that spans detection to suppression of viremia is continued clinic attendance. Our systems for maintaining people in needed health care are anemic and rely on outmoded passive approaches. Engaging patients requires new thinking and the use of available tools that extend beyond a "missed visit" snail mail letter. Creative approaches are being developed and tested to motivate people to attend to their health and overcome competing priorities that form obstacles to care. Clinics too need to soul search and determine if they are welcoming and supportive, rather than intimidating and bureaucratic, and adjust accordingly. Like most things of value, interventions that are effective will cost us money, but chances are they will be worth it.
For this child in Mississippi, it may have all worked out. Other babies who have dropped out of care and not had their infection erased, are not so fortunate. This case suggests that curing our ailing health care system of its failures may be more difficult than curing HIV.
What are some other top clinical developments of 2013? Read more of Dr. Wohl's picks.
David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina and site leader of the University of North Carolina AIDS Clinical Trials Unit at Chapel Hill.