Wednesday, June 29, 2016



A week ago a front page article of the Chronicle reported on a new NIH (National Institute of Health) sponsored clinical research trial to evaluate an experimental antibody to HIV called VRC01 to prevent HIV transmission. The researchers intend to enroll 4,000 vulnerable individuals at high risk of acquiring HIV, including men who have sex with men in the US and South America, 1,500 high risk women in sub-Saharan Africa, and 26 infants at high risk of HIV infection born to HIV infected mothers in the US and Africa. Ironically, it is uncertain whether this research will ever lead to prevention of a single infection. The article states that there is cautious optimism that the results will inform the development of new approaches for HIV prevention including a vaccine for HIV.

The researchers acknowledge that VRC01 has no evidence of preventing HIV in humans and that at the end of the study VRC01 will not be a viable product for HIV prevention in the US or income poor countries because of the high cost of this kind of treatment; low patient acceptability of intravenous injections at four to six week intervals; and the eventual requirement of more than one antibody for a mutating virus that will trigger additional large and costly studies. The VRC01 phase two study which plans to enroll 4,000 individuals internationally—many of whom are illiterate and will be required to sign “informed consent” forms that often exceed twenty pages. The study will cost in excess of $200 million and is eight times larger and twelve times more costly than an average phase two NIH or pharmaceutical company study. It is surprising therefore that a study of this magnitude was approved at a time when NIH is requesting additional funding for other urgent public health issues.

The study design conflicts with universal recommendations by major public health agencies such as WHO and the US Public Health Service (PHS) who recommend immediate post exposure prophylaxis (PEP) or preexposure prophylaxis (PrEP) with antiretroviral drugs for individuals at high risk of HIV infection. Baffling is why 3,000 men exposed to HIV are assured of PrEP in the study’s proposal, while the 1,000 African women are not. Equally perplexing is how the institutional review boards (IRBs), that are supposed to oversee the ethics and study designs, could have approved a study that dismissed standard of care recommendations to immediately provide PEP to protect infants born to HIV infected mothers from HIV infection. Instead researchers will be allowed to delay lifesaving prevention until after an experimental drug of unknown benefit is administered. Additionally, even though the researchers and the IRBs acknowledged that the research is of no known benefit to the infants but of significant risk for acquiring progressive or fatal HIV infection, they allowed the study to proceed. The Office for Human Research Protections (OHRP) federal regulation prohibits research in children that is of no known benefit but significant risk to children. Yet, as unfortunately has been the case previously, OHRP has not intervened. As a result, it is likely that some of these innocent infants will be infected with the HIV virus and develop AIDS, a disease for which there is no known cure.

Certainly no one would oppose finding a silver bullet to stop HIV, but this study seeks to expose thousands of individuals, many of whom are vulnerable and subject to exploitation, to a research product that lacked independent outside scientific review, and ignores WHO and US PHS guidelines for HIV prevention and OHRP regulations for research in children.   If we are to be successful in ending the HIV epidemic the most important research priorities must be identified and rigorous scientific scrutiny with high ethical standards applied.  No matter the urgency of a health crisis or the stated importance of a scientific research question, we have learned from the past that the price of compromising high quality science and sound ethical principles is too high.  When this fails, it will also engender the kind of mistrust that will echo for decades. 

The foregoing blog is an edited version by Kerry Gough of an op-ed authored by Arthur J. Ammann, Pediatrician and advocate for the health of vulnerable children for more than 50 years; Susan M. Reverby, an historian at Wellesley College, and author of Examining Tuskegee: The Infamous Syphilis Study and its Legacy and Kerry Gough, an attorney, author, and reviewer of legal and ethical issues of clinical research.