Resistance to HIV infection - How a Mutation May Help Fight AIDS

A rare genetic mutation called CCR5-Δ32 deletes the doorway HIV uses to enter immune cells, so people who inherit two copies are largely protected from the most common strain. Doctors have turned this biology into a real drug (maraviroc) and a handful of transplant cures. It's not yet a scalable cure for HIV.

The CCR5-Δ32 mutation: what it is and how it blocks HIV

HIV uses a key-and-lock system to enter immune cells. The virus latches onto a main receptor called CD4 on the surface of certain white blood cells, then needs a second "co-receptor" to actually fuse with the cell and get inside. For the strains that dominate early infection, that co-receptor is CCR5.

CCR5-Δ32 is a small deletion in the gene that builds the CCR5 receptor. The "Δ32" means 32 base pairs of DNA are missing. The result is a truncated protein that never makes it to the cell surface. With no CCR5 doorway, the virus arrives but can't get in. Rather than slowing HIV down, the mutation removes the specific molecule the most common HIV variants depend on to start an infection StatPearls.

Some HIV strains use a different co-receptor, CXCR4, instead of CCR5. People without working CCR5 aren't protected from those variants, so CCR5 blockade is powerful but not absolute.

Why some people are naturally resistant (and how rare it is)

You get one copy of the CCR5 gene from each parent, so three combinations are possible. People with two mutated copies (homozygous Δ32) make essentially no functional CCR5 and are highly resistant to CCR5-using HIV. People with one mutated copy (heterozygous) still produce some receptor, are not immune, but tend to progress more slowly if they do get infected. People with two normal copies have no built-in protection.

The double-copy version is uncommon and clusters in people of Northern European ancestry; it's rare or absent in many other populations. The resistance is real, but it protects a small minority, and even then only against the CCR5-tropic strains. Most people don't carry this shield.

CCR5 as a drug target: maraviroc

If a missing receptor protects people, could a drug block it too? That's the idea behind maraviroc, a CCR5 antagonist. It binds the CCR5 receptor and physically gets in the way, so HIV can't use it as a co-receptor. It's one tool among many in modern antiretroviral therapy (ART), not a first-line standby, and it only works against CCR5-tropic virus. Clinicians run a tropism test first to confirm the patient's virus actually uses CCR5.

Maraviroc showed that the resistance seen in Δ32 carriers can be partly mimicked with medicine. But blocking a receptor with a daily pill isn't the same as not having the receptor at all, which is where the transplant cases come in.

The cure cases: Berlin, London, and later patients

A small number of people have been documented in long-term HIV remission after stem-cell (bone-marrow) transplants: the Berlin patient, the London patient, and a New York woman who became the third documented case and the first woman, reported by the NIH in 2022 NIH, 2022. Each received donor stem cells carrying two copies of CCR5-Δ32.

These patients all needed transplants to treat cancer or leukemia, which was the medical reason rather than HIV. By using a donor whose immune cells lacked working CCR5, doctors rebuilt the patient's immune system out of cells HIV couldn't infect through that doorway. With the virus unable to reseed a new CCR5-dependent reservoir, several have stayed off ART without the virus rebounding NIAID.

That the third case was the first woman matters scientifically and for equity. Much cure research has skewed toward men, and confirming the approach across different patients strengthens the proof of concept HHS.

Why this isn't a scalable cure yet

These outcomes are landmark science, but they are not a treatment your clinic can offer. A stem-cell transplant is a high-risk, sometimes life-threatening procedure that requires wiping out a person's existing immune system and rebuilding it. No doctor would put a healthy, well-controlled person with HIV through that just to stop daily pills, because the risk wildly outweighs the benefit when ART already enables a near-normal life.

There are practical barriers too. Matched donors who happen to carry two copies of the rare CCR5-Δ32 mutation are extraordinarily hard to find, and the procedure is enormously expensive and complex. These cures happened because the patients needed transplants anyway. They prove that removing CCR5 can lead to remission, but they don't scale to the more than a million Americans living with HIV CDC, 2023.

What CCR5 research means for a future cure

An HIV cure is an active research goal, not a current option, and the main obstacle is the latent reservoir, pools of dormant, infected cells that ART can't reach and that reignite the virus the moment treatment stops NIAID. The transplant cases hint at a workaround: if you could make a person's own immune cells CCR5-negative without a transplant, you might get the protective effect without the danger.

That's the promise of gene editing. Researchers are exploring ways to edit the CCR5 gene in a patient's own cells, alongside other experimental strategies: latency-reversing "shock and kill" approaches, broadly neutralizing antibodies, and therapeutic vaccines. None of these is an available cure today. Scientists also distinguish a sterilizing cure (clearing every replication-competent virus from the body) from a functional cure (the virus persists but stays controlled without ongoing ART); CCR5-based strategies are mostly aimed at the functional end of that spectrum.

What this means for people with HIV today

There's currently no cure for HIV, and an undetectable viral load means control rather than eradication, since latent reservoirs persist and the virus rebounds if treatment stops HHS. But what's available now is good. A 20-year-old who starts treatment before their CD4 count falls below 200 now has a life expectancy approaching that of the general population Lancet HIV.

Treatment is also prevention. Undetectable equals untransmittable (U=U): a person on ART who stays virally suppressed will not transmit HIV to sex partners. Across the PARTNER studies, mixed-status couples logged tens of thousands of condomless sex acts with zero linked transmissions while the partner with HIV was undetectable PARTNER. Most people reach undetectable within months of starting ART, which is why earlier HIV treatment lowers new infections across a whole community.

For people without HIV, the prevention toolkit keeps improving: daily and on-demand PrEP, the long-acting cabotegravir shot, and newer options like twice-yearly lenacapavir, which produced zero infections among women in the PURPOSE 1 trial WHO. None of this depends on a rare mutation, and it's available now.

When to see a clinician

If you think you were just exposed, act fast. PEP (post-exposure prophylaxis) can prevent infection but must start within 72 hours and runs for 28 days, so it's a same-day urgent-care or ER conversation rather than a wait-and-test one CDC. PrEP is the forward-looking option for ongoing risk CDC.

For everyone else, the USPSTF gives HIV screening a Grade A recommendation: test all adolescents and adults at least once, and repeat for those at higher risk USPSTF. Early flu-like symptoms after a possible exposure are worth an urgent test, since that's when the virus is most contagious. If you're not sure how soon a test will be accurate, read when to test after exposure, then get tested.

Keep exploring on EasySTD: compare testing services, STD incubation periods and HIV/AIDS testing.