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[Immunology](https://durgical.com/en/immunology/) · [Immunodeficiencies](https://durgical.com/en/immunology/#a-immunodeficiency)

# How HIV destroys CD4 T cells

- Process

HIV enters and destroys the helper T cells that coordinate immunity. As their number falls, germs that are harmless to healthy people cause disease.

Updated 2026-11-01

## Key points

- gp120 binds CD4 plus CCR5 (early) or CXCR4 (late); gp41 fuses.
- Latent provirus in memory CD4 cells = reservoir = no cure.
- AIDS: CD4 below 200 cells per microlitre or an AIDS-defining illness.
- Thresholds: below 200 Pneumocystis; below 100 Toxoplasma and Cryptococcus; below 50 CMV retinitis and MAC.
- Massive early loss of CD4 cells occurs in the gut, not in the blood.
- Infant diagnosis uses viral nucleic acid tests, not antibodies.

## What it is

HIV is a retrovirus that infects cells carrying CD4 together with a chemokine co-receptor (CCR5 or CXCR4): mainly helper T cells, macrophages and dendritic cells. It copies its RNA into DNA, inserts it into the host genome and persists as a latent reservoir. Over years, direct killing, inflammatory cell death and chronic immune activation deplete CD4 T cells until the immune system can no longer control opportunistic infections and some cancers (AIDS). The CD4 count predicts which infections are likely.

## Key facts

- The viral reservoir of latent provirus in resting memory CD4 cells is why antiretroviral therapy controls HIV but does not cure it.
- People homozygous for the CCR5-Δ32 deletion are highly resistant to CCR5-using strains.
- Loss of gut CD4 cells weakens the mucosal barrier; microbial products leaking into the blood drive chronic immune activation.
- The CD4/CD8 ratio inverts; B cells are activated non-specifically, so immunoglobulins rise even though specific responses are poor.
- With effective antiretroviral therapy the viral load becomes undetectable, CD4 counts recover and the virus is not transmitted sexually.

## Step by step

- The envelope protein gp120 binds CD4, then a co-receptor: CCR5 (strains transmitted between people) or CXCR4 (strains that often appear later).
- gp41 fuses the viral and cell membranes; the viral core enters the cytoplasm.
- Reverse transcriptase copies viral RNA into DNA with many errors, so the virus mutates fast and escapes antibodies and T cells.
- Integrase inserts the viral DNA into a host chromosome (provirus); in resting memory CD4 cells it can stay silent for years.
- Acute infection: very high viraemia and massive loss of memory CD4 cells in gut lymphoid tissue; often a flu-like illness.
- CD8 T cells and antibodies lower the viral load to a set point, but do not clear the virus (clinical latency).
- CD4 cells keep falling through viral killing, pyroptosis of abortively infected cells, CTL killing and chronic immune activation.
- Below about 200 CD4 cells per microlitre (or with an AIDS-defining illness) the person has AIDS: opportunistic infections and cancers appear.

## CD4 count and typical opportunistic infections (cells per microlitre; tuberculosis can occur at any count)

| CD4 count | Typical infections and cancers | Organism |
| --- | --- | --- |
| [Any count, more frequent below 500](https://durgical.com/en/conditions/tuberculosis/) | Tuberculosis, oral candidiasis, herpes zoster, bacterial pneumonia, Kaposi sarcoma | M. tuberculosis, Candida, varicella-zoster virus, pneumococcus, HHV-8 |
| Below 200 | Pneumocystis pneumonia | Pneumocystis jirovecii |
| Below 150 | Disseminated histoplasmosis (common in Latin America) | Histoplasma capsulatum |
| Below 100 | Toxoplasma encephalitis, cryptococcal meningitis, oesophageal candidiasis | Toxoplasma gondii, Cryptococcus neoformans, Candida |
| Below 50 | Cytomegalovirus retinitis, disseminated Mycobacterium avium complex, primary CNS lymphoma | Cytomegalovirus, M. avium complex, Epstein-Barr virus |

## Markers

- CD4
- CCR5
- CXCR4
- gp120
- gp41
- p24
- reverse transcriptase
- integrase

## Clinical notes

- In Colombia, tuberculosis and histoplasmosis are frequent AIDS-defining illnesses, together with Pneumocystis pneumonia, toxoplasmosis and cryptococcosis.
- Starting antiretroviral therapy can unmask or worsen an infection as immunity returns (immune reconstitution inflammatory syndrome).
- Prophylaxis against opportunistic infections is chosen according to CD4 thresholds (this page does not give treatments or doses).

## In the lab

- Screening: fourth-generation immunoassay (HIV-1/2 antibodies plus p24 antigen), confirmed by a differentiation assay and viral load.
- Viral load (HIV RNA by PCR): activity of the virus and response to treatment.
- CD4 count by flow cytometry: degree of immunodeficiency and risk of opportunistic infections.
- In infants of mothers with HIV, diagnosis is by viral nucleic acid tests because maternal IgG crosses the placenta.

## Memory aid

200 opens the door to Pneumocystis; 100 lets in Toxo and Crypto; below 50 CMV looks through the eyes and MAC takes over the house.

## Test yourself

Think of the answer, then tap the question to see it.

## Which two cell molecules does HIV need to enter a helper T cell?

CD4 and a chemokine co-receptor, CCR5 or CXCR4.

## Why does antiretroviral therapy not eliminate HIV?

Integrated, silent provirus in long-lived resting memory CD4 cells (the reservoir) is not touched by the drugs and can restart replication.

## Below which CD4 count does the risk of Pneumocystis pneumonia rise sharply?

Below about 200 cells per microlitre.

## Where is the largest early loss of CD4 T cells in acute HIV infection?

In the gut mucosal lymphoid tissue, where most CCR5+ memory CD4 cells live.

## Why are antibody tests not used to diagnose HIV in young infants of mothers with HIV?

Maternal IgG crosses the placenta and can stay for months; viral nucleic acid tests are used instead.

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## Related

- [CD4⁺ helper T cell](https://durgical.com/en/immunology/cd4-helper-t-cell/)
- [Secondary immunodeficiency: HIV, malnutrition, drugs, asplenia](https://durgical.com/en/immunology/secondary-immunodeficiency-hiv-malnutrition-drugs-asplenia/)
- [Immunodeficiency: warning signs and the infection pattern by defect](https://durgical.com/en/immunology/immunodeficiency-warning-signs-and-the-infection-pattern-by-defect/)
- [Flow cytometry and the CD4 count](https://durgical.com/en/immunology/flow-cytometry-and-the-cd4-count/)
- [Serology: IgM vs IgG, seroconversion, avidity](https://durgical.com/en/immunology/serology-igm-vs-igg-seroconversion-avidity/)
- [ELISA, western blot and rapid tests](https://durgical.com/en/immunology/elisa-western-blot-and-rapid-tests/)

## Related conditions

- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)
- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)

## Microorganisms

- [Human immunodeficiency virus](https://durgical.com/en/microbiology/human-immunodeficiency-virus/)
- [Pneumocystis jirovecii](https://durgical.com/en/microbiology/pneumocystis-jirovecii/)
- [Toxoplasma gondii](https://durgical.com/en/microbiology/toxoplasma-gondii/)
- [Cryptococcus neoformans](https://durgical.com/en/microbiology/cryptococcus-neoformans/)
- [Cytomegalovirus](https://durgical.com/en/microbiology/cytomegalovirus/)
- [Mycobacterium tuberculosis](https://durgical.com/en/microbiology/mycobacterium-tuberculosis/)
- [Candida albicans](https://durgical.com/en/microbiology/candida-albicans/)
- [Histoplasma capsulatum](https://durgical.com/en/microbiology/histoplasma-capsulatum/)

[← All of immunology](https://durgical.com/en/immunology/)

Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: [About HIV](https://www.cdc.gov/hiv/about/index.html) (Centers for Disease Control and Prevention (CDC), 2026); [25.3 Viral Infections of the Circulatory and Lymphatic Systems](https://openstax.org/books/microbiology/pages/25-3-viral-infections-of-the-circulatory-and-lymphatic-systems) (OpenStax (Microbiology), 2016); [19.4 Immunodeficiency](https://openstax.org/books/microbiology/pages/19-4-immunodeficiency) (OpenStax (Microbiology), 2016).

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