New Technique Offers Hope of Controlling HIV Without Drugs

A new report from the National Institute of Health  suggests that 'gene editing' — removing cells from HIV patients, modifying them and replacing the cells — offers new hope in controlling the virus without drugs.

HivThe NIH reports, via press release:

Scientists today report initial results from humans on the safety and tolerability of a novel strategy to curb HIV disease by removing key cells from HIV-infected individuals, genetically modifying the cells to resist HIV infection and returning them to those people. The basic and pre-clinical research on this strategy, which eventually might help people control the virus without drugs, was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The Phase I clinical trial was funded by Sangamo BioSciences and was led by NIAID grantee Carl H. June, M.D., with co-investigators Bruce L. Levine, Ph.D., and Pablo Tebas, M.D., all of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia.  

The trial built on the observation that people who naturally have a genetic modification in a protein called CCR5 are resistant to HIV infection, and when infected with HIV, progress to AIDS more slowly. CCR5 is a cell-surface molecule, or receptor, that most HIV variants must use to enter their primary target: the CD4T cell. In the trial, CD4+ T-cells were collected from each of 12 HIV-infected volunteers whose virus was controlled by anti-HIV therapy. These cells were then treated in the laboratory with molecular tools called zinc-finger nucleases (ZFNs). The ZFNs were designed to snip the DNA within the gene that codes for the CCR5 receptor. This process introduced a genetic mutation rendering CCR5 receptors non-functional. Subsequently, the cells were stimulated to multiply, and each patient received an infusion of 10 billion of their own CD4+ T-cells, with roughly a fifth of the CCR5 genes now mutated.

Four weeks later, in a planned interruption of anti-HIV therapy, half the study participants stopped taking their antiretroviral drugs for 8 to 12 weeks. Investigators found that the experimental treatment was generally safe, and that the genetically modified cells appeared to be protected from HIV infection. In one volunteer who naturally had the desired mutation in half of his CCR5 genes, HIV replication was controlled during the entire 12-week treatment interruption. Future research will include evaluating this experimental treatment in more volunteers, as well as maximizing the frequency of CCR5 disruption by ZFNs and increasing the persistence of the genetically modified cells in the body to achieve a therapeutic effect.

Said Dr. Anthony Fauci, director of the NIAID, to the NYT:

“It’s a great strategy. It’s exciting, interesting, elegant science. But a lot of ‘ifs’ need to be addressed before you can say ‘Wow, this could really work.’”

The paper adds: "Dr. Fauci also questioned whether patients would want this relatively complex treatment when many people can keep the infection under control with just one to a few pills a day."

In related news, a new study on viral load transmission reported some interesting findings:

The second large study to look at whether people with HIV become non-infectious if they are on antiretroviral therapy (ART) has found no cases where someone with a viral load under 200 copies/ml transmitted HIV, either by anal or vaginal sex.

Statistical analysis shows that the maximum likely chance of transmission via anal sex from someone on successful HIV treatment was 1% a year for any anal sex and 4% for anal sex with ejaculation where the HIV-negative partner was receptive; but the true likelihood is probably much nearer to zero than this.

When asked what the study tells us about the chance of someone with an undetectable viral load  transmitting HIV, presenter Alison Rodger said: "Our best estimate is it's zero."


  1. Gary says

    The press release isn’t entirely clear about how Sangamo’s gene therapy works or what its benefits would be. People who are homozygous for the CCR5-Δ32 mutation don’t express the CCR5 membrane protein at all, making them entirely immune to most strains of HIV, which require the CCR5 protein to enter a cell. There are some strains of HIV that use the CXCR4 protein and are unaffected by the CCR5-Δ32 mutation, but these are far rarer than the CCR5-tropic strains. Some, but not all, slow progressors are heterozygous for the same mutation.

    The early trials have modified CD4 T-lymphocytes from patents’ blood in order to study the effect of the gene therapy on CD4 T-lymphocyte mortality and viral suppression during a treatment interruption. That’s the “complex treatment” described in the press release, since repeated blood transfusions would be required over a patient’s lifetime to maintain immune fuction using genetically-modified blood transfusions. The ultimate goal is to use the same gene therapy in autologous stem cell transplants. By supllying stem cells from the patient’s own bone marrow that are homozygous for the CCR5-Δ32 mutation, the treatment would replicate the Berlin Patient’s functional cure after a single transplant and without any risk of graft vs. host disease. Compared to a lifetime of ART, the transplant of genetically-modified cells would be simpler and cheaper, requiring no antiretroviral medication and no long-term follow-up.

  2. Gordon says

    Why, when already within my generation there are “bug chasers” & youth HIV high with the response that it’s treatable with meds, in an ‘advanced country’, are we relying on DNA from 12 people to provide a genetic response rather than simply wearing a condom?

  3. Bill says

    @Gordon: they are studying the response of 12 people to see if there is anything worth pursuing.

    If they find an effective treatment that doesn’t require drugs (they seem to have promising results so far), and cost of that treatment is less than the lifetime costs of antiviral drugs, we’ll save a bundle on medical care.

    It is not an alternative to condoms.

  4. B. Wilson says

    The viral load (VL) study is very important as well. With proper antiretroviral therapy a person’s VL can almost always be reduced to less than 40 copies/. The study shows that as long as the viral load is kept below 200 a person is extremely unlikely to transmit the virus through sexual intercourse (though I’d need to check the weighting in the analysis on vaginal v anal sex to be better informed). All in all, though, perhaps the final proof of treatment as prevention.

  5. Bill says

    @Roger: during the Middle Ages, there were a couple of theories about what caused the plague. On was that it was caused by Muslims and Jews – that theory was popular among Christians. Another was that it was caused by Christians and Jews – that one was popular among Muslims. Being outnumbered, the local Jewish population though twice about blaming Christians and Muslims and decided that discretion was the better part of valor. Meanwhile nobody thought about the rats.

    One preacher ordered his “sheeple” to stay in church and pray for deliverance. Naturally they had to bring food. The food attracted the rats, which carried the fleas that carried the plague, and the whole congregation died.

    In this day and age you should know better, which makes you far worse than that preacher, who didn’t know what to do because nobody at the time did.

  6. snork says

    press release, press release, press release.

    no getting around the fact that current crop of senior HIV researchers have FAILED and should no longer be funded. It’s time for a new crop.

  7. B. Wilson says


    The world over we have learned that condoms simply aren’t enough. There are a variety of psychosocial issues that impede the consistent use of condoms. It’s not about replacing condoms…it’s about increasing the variety of tools we have to fight the disease (/prevent transmission). New barrier method technologies are needed that work alone or in tandem with condoms for both vaginal and anal sex. Increasing quality of life and reducing infectiousness of the person living with HIV, increasing the defences/resources of a person at risk for HIV, finding new and alternate technologies to assist in prevention (barriers), and a collective deep breath.
    We may still all make it through this…..

  8. Gregory in Seattle says

    @Gordon – The research is based off of recent findings involving a very tiny group of people called long-term non-progressors. Those are people who get diagnosed with HIV but who never see the immune system collapse that results in AIDS. LTNPs have been the focus of considerable study since it was found that some people seem naturally resistant to the virus, and two different genetic variances have been found.

    This group have a very rare variance in the protein that HIV uses to hoist itself into the cell: it is… well, shaped funny. It fulfils its function, but it is odd enough that HIV has trouble using it. Enough viruses get in to create a permanent infection, but so few that the immune system that fights viruses never gets overwhelmed. That is why only 12 people.

    What this study seems to indicate is that we should be able to extract cells from a person without this mutation, alter the genes in the cells to give them this mutation, then put them back. The cells will replicate, granting heightened immunity. It is similar to what was done to the “Berlin Patient,” the first person proven to be cured of HIV.

    Before we get too excited, though, keep in mind the cost. This basic procedure has been in use for about 10 years as a way of treating other conditions. Each procedure can cost upwards of $150,000, and the first procedure doesn’t always give strong results. Thus, it will never be something that you can just pop down to the clinic and get while on your lunch break.

  9. Gregory in Seattle says

    @snork – HIV is tricky: it attacks one part of the immune system in a way that lets it hide from the rest. We have learned a great deal about the virus since it was first discovered about 28 years ago, and we have had effective treatments against it for 20 years. HIV related research has led to other advances in medicine, from timed-release drugs to antivirals for diseases like shingles and herpes to new avenues of genetic engineering like the one Andy posted. We are now closing in on ways to fight it that will not require life-long drug therapy.

    How can you possibly spin that as a failure?

  10. Rrhain says

    How is this different from the two Boston patients that received bone marrow transplants? They, too, were seemingly HIV-free for months only to have the virus return. None of the articles that I see about them indicate what it was about the bone marrow that was received that would have conferred immunity.

    On top of that, there is a variant of HIV that doesn’t use CCR5. The articles I read say that this strain tends to not present itself in patients with a functioning immune system, but they also caution that this is by no means a guarantee.

    Plus, the treatment for the Berlin patients required a bone marrow transplant which is extremely risky. Essentially, they have to destroy your current bone marrow (which makes you highly susceptible to disease) in order to prep your body for the transplant. And there is always the chance for rejection.

    Keep working at it. This is promising research, but we need to be extremely careful about calling this a “cure” by any stretch.

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