A 32-base-pair deletion in the CCR5 gene that removes a key HIV-1 entry receptor from immune cells; two copies confer strong resistance to CCR5-tropic HIV-1, while one copy slows disease progression without preventing infection.
Most cells in the body carry a small protein called CCR5 on their surface. Its normal job is to receive chemical signals (chemokines) that guide immune cells to sites of inflammation. HIV-1 has evolved to exploit that same docking site: to get inside a CD4 T cell or macrophage, the virus must first grip the CD4 receptor and then latch onto a second "co-receptor," and for the great majority of HIV-1 circulating in newly infected people, that co-receptor is CCR5. Virus that depends on CCR5 in this way is called R5-tropic.
The CCR5-delta32 variant is a 32-base-pair deletion in the CCR5 gene — not a single-letter spelling change, but the loss of a whole chunk of the gene's instructions. The deletion shifts the reading frame partway through the gene, so the cell builds a truncated, garbled protein that never reaches the cell surface. A person who inherits this deletion from both parents has essentially no functional CCR5 on their immune cells. Because R5-tropic HIV-1 cannot find its usual foothold, these individuals are strongly resistant to infection by the strains of HIV-1 that dominate the global epidemic, including in people who have had repeated high-risk exposure.
Inheriting just one copy is a different story. Heterozygotes still make roughly half the normal amount of CCR5 and can absolutely be infected with HIV-1. What one copy changes is the pace of disease afterward: on average, heterozygotes who become infected progress to AIDS about two to three years more slowly than people with two normal copies, likely because having less CCR5 available slows how efficiently the virus spreads through the immune system. Slower progression is a real, well-documented benefit — but it is not protection, and it is not a reason to think of oneself as harder to infect.
This is the point that gets lost in popular retellings, so it deserves to be stated without hedging: CCR5-delta32, even in double copy, is not a reason to consider anyone immune to HIV, and it is not a reason to change any decision about testing, prevention or safer sex. The protection is specific to viruses that use CCR5 to enter cells. A minority of people living with HIV-1, usually later in the course of untreated infection, harbor virus that has switched to using a different co-receptor, CXCR4 — so-called X4-tropic virus. CCR5-delta32 does nothing to block X4-tropic HIV-1, and CCR5-delta32/delta32 individuals have been infected by it. Genotype at this one locus also says nothing about a person's risk from other sexually transmitted infections. Nobody should use this variant, or a report describing it, as a basis for skipping condoms, PrEP, or routine testing.
CCR5-delta32 moved from a laboratory curiosity to a household name because of stem-cell transplantation. In 2007, a man living with HIV-1 who also had acute myeloid leukemia (later known publicly as the "Berlin patient") received a bone marrow transplant from a donor who happened to carry two copies of CCR5-delta32. The transplant was done to treat his leukemia, but doctors deliberately chose a CCR5-delta32/delta32 donor in the hope it might also help his HIV. After the transplant rebuilt his immune system with CCR5-less cells, he was able to stop antiretroviral therapy and stayed free of detectable virus for years, an outcome documented in detail by his medical team. In 2019, a second person (the "London patient") achieved a similar sustained remission after an analogous transplant for lymphoma, using a less intensive conditioning regimen, showing the first case was not a one-off. A handful of other people transplanted from CCR5-delta32/delta32 donors for unrelated cancers have since been reported with comparable outcomes. These are not a template for treating HIV in general — the transplants themselves carry serious risks and were performed to treat life-threatening cancers, not simply to cure HIV — but they are proof of principle that removing functional CCR5 from the immune system can produce durable viral control.
Chemokine receptors are not evolutionary accidents; CCR5 also participates in the immune response to other pathogens, so researchers have looked hard for trade-offs. The most studied is West Nile virus: several U.S. cohort studies found that people homozygous for CCR5-delta32 were over-represented among those who developed symptomatic, sometimes severe, West Nile virus disease, consistent with a role for CCR5 in controlling that infection in the central nervous system. The finding has not been perfectly consistent, however — at least one independent study failed to replicate an association — so it is fair to describe this as a real signal from multiple studies rather than a settled, universally reproduced fact. Whether the deletion measurably affects susceptibility to other infections, including tick-borne encephalitis, remains an active and less settled area of research. None of this changes the HIV story; it is simply a reminder that a variant which is protective against one pathogen is rarely protective against everything.
CCR5-delta32 is essentially a European-ancestry variant. It is found on roughly one in ten chromosomes across European populations (somewhat higher in northern and eastern Europe, lower around the Mediterranean), and is rare to essentially absent in sub-Saharan African, East Asian and Indigenous American populations. Genetic studies of the surrounding DNA suggest all copies trace back to a single ancestral deletion event on one chromosome, later spread by ordinary population history rather than arising independently many times.
CCR5 (chromosome 3p21.31) encodes a seven-transmembrane G-protein-coupled beta-chemokine receptor expressed on CD4+ T lymphocytes, macrophages, dendritic cells and microglia. Together with CD4, CCR5 serves as the principal entry co-receptor for CCR5-tropic ("R5") strains of HIV-1, which predominate during transmission and early infection; a subset of viruses uses CXCR4 instead ("X4" or dual/mixed-tropic strains), typically emerging later in untreated disease.
The variant catalogued as rs333 is a 32-base-pair deletion (reference transcript NM_001394783.1:c.554_585del; protein NP_001381712.1:p.Ser185fs; genomic GRCh38 NC_000003.12:g.46373456_46373487del), historically referred to simply as "CCR5-delta32." The deletion removes 32 nucleotides from the coding sequence and produces a frameshift that introduces a premature stop codon; the resulting truncated polypeptide lacks the second extracellular loop and all downstream transmembrane domains, is retained intracellularly, and is not trafficked to the cell surface. Homozygotes therefore display no detectable functional CCR5 on peripheral blood mononuclear cells.
Homozygosity (delta32/delta32) confers strong resistance to acquisition of R5-tropic HIV-1, documented from the earliest reports of multiply-exposed seronegative individuals (Liu et al., 1996) through subsequent cohort studies. Resistance is not absolute in principle, since transmission of X4-tropic or dual-tropic virus, though uncommon at transmission, is not blocked by loss of CCR5, and documented infections in delta32/delta32 individuals with such variants exist.
Heterozygosity (delta32/+) reduces cell-surface CCR5 density by roughly half and is consistently associated with slower progression to AIDS in infected individuals — on the order of two to three years' delay relative to CCR5 wild-type/wild-type individuals across multiple longitudinal cohorts — and with somewhat better virologic response in some antiretroviral treatment studies. Heterozygosity does not meaningfully reduce the probability of acquiring HIV-1 and should not be communicated to patients as protective against infection.
Allele frequency is roughly 0.10 in European-ancestry populations (reported range approximately 0.04 in southern Europe/Sardinia up to 0.16 in Finnish and Mordvinian samples), which by Hardy-Weinberg expectation (allele frequency p, carrier frequency 1-(1-p)²) corresponds to roughly 18-20% of individuals of European ancestry carrying at least one copy and roughly 1% being homozygous — allele frequency should not be read directly as carrier or genotype frequency. The deletion is rare to essentially absent in sub-Saharan African, East Asian and Indigenous American reference panels; haplotype-based analyses are consistent with a single founder deletion event that subsequently spread within European populations, rather than recurrent independent mutation.
The variant underlies two well-documented cases of sustained HIV-1 remission after allogeneic haematopoietic stem-cell transplantation from CCR5-delta32/delta32 donors, performed to treat coexisting haematologic malignancy: Hütter et al. (2009, the "Berlin patient") and Gupta et al. (2019, the "London patient"). Both patients discontinued antiretroviral therapy after transplant and have remained without rebound viremia on extended follow-up. These cases motivated therapeutic strategies aimed at pharmacologically or genetically disrupting CCR5 (e.g., the CCR5 antagonist class of antiretrovirals, and investigational CCR5 gene-editing approaches), which exploit the same biology as the naturally occurring variant. These are research and specialist-treatment contexts, not implications for routine HIV prevention or care in carriers of the variant.
Reported non-HIV associations include increased risk of symptomatic, and in some studies more severe, West Nile virus infection in delta32 homozygotes (Glass et al., 2006, and subsequent meta-analytic work), interpreted as a fitness trade-off consistent with a physiological role for CCR5 in flavivirus control within the central nervous system; this association has not been replicated in every cohort studied, and the underlying mechanism and consistency across populations remain areas of active investigation. Associations between CCR5 genotype and outcomes in multiple sclerosis and certain other inflammatory conditions have also been reported and are of lower certainty.
A report of delta32/delta32 genotype indicates strong resistance to acquisition of CCR5-tropic HIV-1 and, if the person is already living with HIV-1, favors a more indolent disease course; it does not establish immunity to HIV-1 overall, does not indicate anything about X4-tropic virus risk, and does not substitute for HIV testing or standard prevention counseling. A report of a single delta32 copy indicates a modest, population-level association with slower progression if infected and confers no meaningful reduction in the likelihood of acquiring HIV-1.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about CCR5-Delta32 and HIV-1 Resistance comes down to these specific, well-studied positions — not a diagnosis.
No. This is the single most important thing to understand about this variant. Two copies give strong resistance specifically to the CCR5-using ("R5-tropic") strains of HIV-1 that dominate transmission worldwide, but they do nothing against the less common CXCR4-using ("X4-tropic") strains, and people with two copies have been infected by those. Nobody should skip testing, PrEP, condoms or any other prevention step based on this genotype.
Two copies (delta32/delta32) remove functional CCR5 from immune cells almost entirely and are associated with strong resistance to acquiring R5-tropic HIV-1. One copy (delta32/+) roughly halves CCR5 levels but does not meaningfully reduce the chance of infection; its documented benefit is a slower average pace of progression to AIDS, on the order of two to three years, if a person does become infected.
Both were people living with HIV-1 who needed bone marrow transplants for unrelated blood cancers. Their doctors chose donors who happened to carry two copies of CCR5-delta32, and after the transplants rebuilt their immune systems with CCR5-less cells, both were able to stop antiretroviral therapy and have remained free of detectable virus for years. They are the clearest proof that eliminating functional CCR5 can produce durable viral control, though the transplant procedure itself is far too risky to use as routine HIV treatment.
Several studies have found that people homozygous for the deletion are over-represented among those who develop symptomatic, sometimes severe, West Nile virus infection, suggesting normal CCR5 helps control that virus in the nervous system. Not every study has found this association, so it should be considered a credible but not fully settled finding rather than an established certainty, and its size in absolute terms is small given how rare West Nile virus disease is.
Yes. The deletion is found on roughly one in ten chromosomes in people of European ancestry, with some variation across Europe, and is rare to essentially absent in people of sub-Saharan African, East Asian or Indigenous American ancestry. Its geographic pattern is consistent with a single ancestral deletion that arose once and spread within European populations.
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