The ethical case for placebo control in HIV-cure-related studies with ART interruption
Publication Date: 09/01/2022
Introduction
There is consensus about the continuing need for an analytical treatment interruption (ATI), a period following the investigative intervention in which the participant does not take ART, in many HIV cure-related studies.1 By “HIV cure” we mean either sterilization—expunging the virus from the body; or remission—a period without detectable virus and without symptoms, absent antiretroviral treatment (ART), although HIV remains in the body.2 It is only thanks to the ATI that researchers can see whether sterilization or remission has taken place.
Some completed, ongoing, or planned HIV cure-related studies, typically early-phase, include control arms where participants receive either a placebo substance or simply no intervention. For brevity, we refer to either form of control as “placebo”. in a cure-related study without an ATI, the participants on “placebo” would remain on standard of care, namely, ART. Obviously, in studies with an ATI, during that ATI, participants on “placebo” would not receive standard of care.
While there also seems to be a consensus about the scientific value of placebo control in cure-related studies, on grounds relayed below, in HIV cure conferences some investigators expressed doubt that it can ever be ethical to include a placebo arm in cure studies that involve an ATI. In other words, while both placebos and an ATI are individually acceptable, the combination of placebo and an ATI is sometimes said to be beyond the pale, ethically.