Designing HIV-Resistant People: A Top HIV Clinical Development of 2018

As unsavory as probably it is to most of us, there's big news in the claim by He Jiankui, Ph.D., that he was able to use Crispr-Cas9 technology to alter the genes of twin girls so they were born with their CD4 cells not expressing the CCR5 co-receptor that HIV primarily uses to gain cellular entry.

First, there is the technical feat, which if verified is a landmark. If this actually happened, He was able to edit the genes of two embryos so that all their cells are changed. This means that the genes they pass on to their own children would also be the edited versions. Apparently, only one of the twins had both copies of the CCR5-deleting genes. For the other, only one copy of this gene was deleted, and therefore, CCR5 would still be expressed by some of her CD4 cells.

More significant are the ethical aspects, which have gotten most of the attention. The safety of editing genes is not known, and there are legitimate concerns that, inadvertently, other genes that are consequential to health could have been altered or removed. Even if this did not occur, CCR5 deletion is associated with some negatives, including more severe disease when infected with West Nile Virus, Japanese Encephalitis, and perhaps other infections. Further, these infants never consented to having their DNA altered by He, raising serious issues about the right to be born with the genes you are dealt, especially if there was nothing obviously wrong with them.

What is sometimes missed in the swirling ethical debate this has provoked is the rationale for making these infants HIV-proof. It is reported that their father is HIV positive, but that their mother is not. That He chose to perform his experiment on children whose father is HIV positive signals that he somehow poses a risk to them -- which, of course, is preposterous. The genes of these girls have been manipulated to protect them from a menace that does not exist; any future risk of HIV acquisition they face can be better and more safely be addressed by standard HIV prevention methods. Certainly, He knows this.

So, why did he do it? I suspect it's because he could.

The Bottom Line

In addition to the outrage over editing the genes of healthy embryos, which is illegal in the U.S. and may carry significant risk to these children and their offspring, people living with HIV and their allies should strongly oppose He and condemn his cloaking of this work with the nobility of combating HIV. The worthy cause of preventing HIV cannot be used to justify scientific recklessness. If it is true this has been done, and that a Chinese HIV advocacy group helped him recruit the parents, the worldwide HIV community must add its voice and condemn He and this organization.

Top 10 Clinical Developments of 2018
0. Introduction
1. GEMINI and the Rise of Two-Drug HIV Therapy
2. Debate Over Dolutegravir in Early Pregnancy
3. Integrase Inhibitors and Weight Gain
4. PrEP and the Decline in New HIV Diagnoses
5. On-Demand Prevention in France
6. Bictegravir Has Finally Arrived
7. Abacavir, Platelets, and a Cardiovascular Verdict
8. African-American Men and HIV Treatment Outcomes
9. The Long-Acting Bandwagon
10. Designing HIV-Resistant People

David Alain Wohl, M.D., is a professor of medicine in the Division of Infectious Diseases at the University of North Carolina (UNC). He is site leader of the UNC AIDS Clinical Trials Unit at Chapel Hill, director of the North Carolina AIDS Education and Training Center (AETC), and co-director of HIV services for the North Carolina state prison system. In 2014, he became co-director of the UNC-Duke Clinical RM Ebola Response Consortium.