HIV Remission in Neonates: Ethical and Human Rights Considerations

A published case report of an infant who inadvertently developed remission of HIV viral expression has prompted research to determine if this observation is reproducible and can offer a potentially novel clinical approach to inducing sustained viral remission of HIV (Shah et al. 2014).

Typically HIV-infected mothers receive antiretroviral therapy (ART) before delivery and infants receive between one and three drugs at “low doses” for prevention. In the case report, the mother delivered before she could receive ART. The infant was placed on a three-drug approach with “higher” doses by her doctor than are typically used for treatment. When HIV infection was confirmed, the three-drug regimen was continued. For most infants, the treatment-dose approach would not have started until HIV infection was confirmed at a week or more of age, and then it would have continued indefinitely. In this case report, the child was lost to follow-up and stopped receiving medications around 15 months of age. When medical care was resumed, plasma viral load and HIV-1 antibody titers were undetectable, suggesting that the child had experienced a viral remission. However, the child ultimately experienced viral rebound 27 months after coming off therapy and has since been placed back on ART.

Investigators are now proposing studies to determine if this is a reasonable clinical strategy. The general design would be to ask women to give permission to enroll their infants in an unblinded, single-arm interventional trial that would begin high-dose triple-drug treatment within 48 hours of birth. Those whose blood samples (taken at birth) were determined to be positive for HIV at one to three weeks of age would continue with the same course for the next two years. At this point, provided an expert panel approved a pause in treatment, ART would be stopped and the infants observed with frequent testing over the next few years to see if viral remission occurred and for how long it lasted. Any HIV infection relapse would be treated according to standard clinical approaches.

This study approach will expose most of the children enrolled (91–98%), who will turn out at age 1 to 3 weeks not to be infected by HIV, to the risks of high-dose ART. The risks of short-term high-dose ART are not known fully, but they appear to include anemia, mitochondrial toxicity, changes in liver function, skin rash, pancreatitis, diarrhea, nausea, and vomiting. The approach will also expose infants who turn out be infected and whose treatment is stopped at 12 months to risks of HIV relapse, which might include HIV drug resistance. However, it is not clear how common or serious this problem will be in this context.

Is this an ethical study design, or could it be improved upon? The proposed design raises a number of important questions. Some authors have addressed whether the initial study should be conducted in a developed country, or whether it would be better to conduct the study in a country with more limited resources and increased HIV prevalence, which would allow the question to be addressed faster. Others have asked whether women who are at higher risk of transmission because of no prenatal ARTs (8% risk) should be the focus of enrollment, compared to those receiving prenatal ART (1–2% risk). Such women may have less education about the risks of HIV and ART, thus affecting their ability to give informed consent, but fewer infants will be exposed to the study approach. However, some additional questions that have not been addressed include the following:

1. 1. If this study is conducted in limited or middle-income countries, enrolled infants may obtain HIV treatment sooner that the de facto standard, which is to receive treatment weeks later. The enrolled infants may also have the opportunity to stop ART for either a limited time or perhaps indefinitely. Will these be seen as opportunities or potential burdens for subjects and the community?

2. 2. Should permission be obtained prenatally or postnatally? Can the infant’s care provider (who is also a researcher) obtain permission, or is...