Medservatory
USMLE Step 1MicrobiologyEP 11 of 14

HIV life cycle and drug targets, step by step

Six steps take HIV from attachment to a mature virion, and antiretroviral drug classes block them. Learn the order, the drugs and why the integrated provirus cannot be cleared.

  • 5:39 video
  • 3 min read
  • 16 sources
  • Published 15 Nov 2026
Video lesson · 5:39 · Watch on YouTubeSeries: Microbiology · @medservatory
Chapters (13)
By the end of this lesson

Trace the HIV life cycle (attachment, fusion, reverse transcription, integration, assembly, maturation) and name the antiretroviral class acting at each step.

The short version

  1. The HIV life cycle runs attach, fuse, copy, insert, build, cut, and there is a drug class at each step.
  2. Entry drugs act at attachment (fostemsavir, binding gp120), after attachment (ibalizumab, binding CD4), at coreceptor binding (maraviroc, binding CCR5) and at fusion (enfuvirtide, binding gp41).
  3. Nucleoside and nucleotide analogues terminate the DNA chain; non-nucleoside inhibitors bind reverse transcriptase directly.
  4. The provirus is a permanent part of the host genome, so drugs cannot clear it and treatment is lifelong.
  5. Treatment combines two or more drugs from different classes, which lowers the chance that drug-resistant virus escapes.

The puzzle: undetectable for years, then the virus returns

A man's HIV viral load has been undetectable for years on treatment. He stops his tablets, and the virus comes back. Where was it hiding?

The answer sits inside the HIV life cycle. This lesson follows the virus step by step, from attachment to maturation, and matches each antiretroviral drug class to the step it blocks. The mnemonic is attach, fuse, copy, insert, build, cut.[4][5]

HIV is a retrovirus that infects CD4 cells

HIV is a retrovirus: it has an RNA genome, and the virion carries three enzymes, reverse transcriptase, integrase and protease.[1][3][4]

It infects cells that carry the CD4 receptor, mainly helper T cells.[2][4][5]

Steps one and two: attachment and fusion, and the entry drugs

Attachment. The surface protein gp120 binds CD4. That changes its shape and exposes a site for a coreceptor, CCR5 or CXCR4.[4][5]

Fusion. The other envelope protein, gp41, pulls the viral envelope and the cell membrane together.[5][6]

Entry drugs and where they act
DrugTargetEffect
Fostemsavirgp120Blocks attachment
Ibalizumab (antibody)CD4, at a different siteBlocks the steps after attachment
MaravirocHost CCR5 coreceptorBlocks coreceptor engagement; works only against virus that uses CCR5
Enfuvirtidegp41Blocks fusion; has to be injected

Maraviroc blocks the host CCR5 coreceptor, so it works only against virus that uses CCR5, not virus that uses CXCR4. Enfuvirtide binds gp41 and has to be injected.[5][6][7][10][11]

Step three: reverse transcription and its inhibitors

Reverse transcriptase copies the RNA genome into DNA.[3][4]

The two reverse transcriptase inhibitor classes
ClassExamplesHow it works
Nucleoside and nucleotide analoguesZidovudine, tenofovir, lamivudineBuilt into the new DNA but lack a 3′-hydroxyl, so the chain cannot be extended
Non-nucleoside inhibitorsEfavirenzBind the enzyme itself and block it without being built in

The first class is incorporated and terminates the chain; the second is not incorporated and binds reverse transcriptase directly.[8][12]

Step four: integration and the permanent provirus

Integrase inserts the viral DNA into a host chromosome, where it is called the provirus. Integrase strand transfer inhibitors, the drugs ending in tegravir, such as dolutegravir, block that insertion.[4][13]

That answers the opening puzzle. The provirus is a permanent part of the cell's genome and can lie silent (latent), and drugs cannot remove it, so when treatment stops, the virus returns.[2][3][6]

Steps five and six: assembly and maturation

Assembly. The host cell makes viral RNA and the Gag and Gag-Pol polyproteins, which gather at the membrane and bud out as an immature virion.[4][6]

Maturation. Protease cuts those polyproteins into working proteins. Protease inhibitors, the drugs ending in navir, such as darunavir, leave an immature virion that cannot infect.[4][14]

Ritonavir is given to boost other protease inhibitors, because it inhibits the liver enzyme CYP3A4.[6][9][15]

The newest class, capsid inhibitors such as lenacapavir, acts on the capsid at several stages.[5][6][16]

The order of the HIV life cycle and combination therapy

  1. Attachgp120 binds CD4 (fostemsavir blocks this; ibalizumab acts after), then a coreceptor (maraviroc blocks CCR5).
  2. Fusegp41 pulls envelope and membrane together. Enfuvirtide.
  3. CopyReverse transcriptase makes DNA. Nucleoside and nucleotide analogues, non-nucleoside inhibitors.
  4. InsertIntegrase builds in the provirus. Integrase strand transfer inhibitors.
  5. BuildGag and Gag-Pol gather and bud as an immature virion.
  6. CutProtease matures the virion. Protease inhibitors.

Treatment combines two or more drugs from different classes, which lowers the chance that drug-resistant virus escapes.[5][6]

Use the order as a map. For any drug, ask which step it blocks: a drug ending in tegravir acts at insertion, and a drug ending in navir acts at maturation.[13][14]

Practice question

Original · USMLE style
Your turnQB-MS-S1-MICRO-010-01

A 41-year-old man with HIV infection has a detectable viral load despite good adherence to therapy. Genotyping shows resistance to several reverse transcriptase inhibitors and protease inhibitors, and a tropism assay shows virus that uses CCR5. A new drug that binds the CCR5 receptor on his CD4 cells is added to his regimen.

Which step of the viral life cycle is most directly blocked by this drug?
Pick one option. Your answers stay on this device.

Common questions

What are the steps of the HIV life cycle?

Attachment, fusion, reverse transcription, integration, assembly and maturation, remembered as attach, fuse, copy, insert, build, cut.

Which HIV drug class acts at each step?

Entry drugs act at attachment and fusion, reverse transcriptase inhibitors at copying, integrase strand transfer inhibitors at insertion, and protease inhibitors at maturation. Capsid inhibitors act at several stages.

How do NRTIs and NNRTIs differ?

Nucleoside and nucleotide analogues are built into the new DNA but lack a 3′-hydroxyl, so the chain cannot be extended. Non-nucleoside inhibitors bind the enzyme itself and block it without being built in.

Why is HIV treatment lifelong?

Integrase inserts the viral DNA into a host chromosome as the provirus. It is a permanent part of the cell's genome and drugs cannot remove it, so the virus returns when treatment stops.

Why is ritonavir given with other protease inhibitors?

Ritonavir inhibits the liver enzyme CYP3A4, so it is given to boost other protease inhibitors.

Transcript

Read the full narration, by chapter635 words

0:00The puzzle: undetectable, then back

A man's HIV viral load has been undetectable for years on treatment. He stops his tablets, and the virus comes back. Where was it hiding? Today: the steps of the HIV life cycle, and the drug class that stops each one.

0:15HIV is a retrovirus; the CD4 target cell

HIV is a retrovirus: an RNA genome, with reverse transcriptase, integrase and protease packed inside the virion. It infects cells that carry the CD4 receptor, mainly helper T cells.

0:30Attachment: gp120, CD4, CCR5 and entry drugs

Step one, attachment. The surface protein gp120 binds CD4. That changes its shape and exposes a site for a coreceptor, CCR5 or CXCR4. Drugs here: fostemsavir binds gp120 and blocks attachment. Ibalizumab, an antibody, binds CD4 at a different site and blocks the steps after attachment. Maraviroc blocks the host CCR5 coreceptor, and works only against virus that uses CCR5.

1:06Fusion: gp41 and enfuvirtide

Step two, fusion. The other envelope protein, gp41, pulls the viral envelope and the cell membrane together. Enfuvirtide binds gp41, and has to be injected.

1:20Reverse transcription, chain termination and non-nucleoside inhibitors

Step three, reverse transcription. Reverse transcriptase copies the RNA genome into DNA. Nucleoside and nucleotide analogues, such as zidovudine, tenofovir and lamivudine, are built into the new DNA but lack a 3'- hydroxyl, so the chain cannot be extended. Non-nucleoside inhibitors, such as efavirenz, bind the enzyme itself and block it without being built in.

1:49Integration: the provirus and integrase inhibitors

Step four, integration. Integrase inserts the viral DNA into a host chromosome, where it is called the provirus. Integrase strand transfer inhibitors, the drugs ending in tegravir, such as dolutegravir, block that insertion. That answers our hook. The provirus is a permanent part of the cell's genome, and drugs cannot remove it, so when treatment stops, the virus returns.

2:18Assembly: Gag and Gag-Pol

Step five, assembly. The host cell makes viral RNA and the Gag and Gag-Pol polyproteins, which gather at the membrane and bud out as an immature virion.

2:30Maturation: protease and protease inhibitors

Step six, maturation. Protease cuts those polyproteins into working proteins. Protease inhibitors, the drugs ending in navir, such as darunavir, leave an immature virion that cannot infect.

2:46Ritonavir boosting and the capsid inhibitor

Ritonavir is given to boost other protease inhibitors, because it inhibits the liver enzyme CYP3A4. The newest class, capsid inhibitors such as lenacapavir, acts on the capsid at several stages.

3:01The order of steps and combination therapy

To remember the order: attach, fuse, copy, insert, build, cut. Treatment combines drugs from different classes, so that a virus resistant to one is still blocked by the others.

3:15Your turn: a practice question

Your turn. A 41-year-old man with HIV infection has detectable viral load despite good adherence. Genotyping shows resistance to several reverse transcriptase inhibitors and protease inhibitors, and a tropism assay shows virus that uses CCR5. A new drug that binds the CCR5 receptor on his CD4 cells is added to his regimen. Which step of the viral life cycle is most directly blocked? A, binding of gp120 to the CD4 receptor. B, binding of gp120 to the coreceptor. C, fusion of the envelope with the cell membrane. D, reverse transcription of the viral genome. E, integration of viral DNA into the host chromosome. Pause here and decide. A is out: a CCR5 antagonist does not touch gp120 binding to CD4. Fostemsavir, which binds gp120, blocks that attachment step; ibalizumab binds CD4 but acts after attachment. C is out: fusion is blocked directly by enfuvirtide, which binds gp41. Blocking the coreceptor acts one step earlier. D is out: reverse transcription is blocked by nucleoside and non-nucleoside inhibitors. E is out: integration is blocked by the integrase strand transfer inhibitors.

4:51The answer: coreceptor binding

So the answer is B. Maraviroc binds the host CCR5 receptor, so gp120 cannot engage its coreceptor after it has bound CD4.

5:04Recap pocket card and next lesson

Three things to keep. One: attach, fuse, copy, insert, build, cut, with an entry, reverse transcriptase, integrase, protease or capsid drug class at each step. Two: nucleoside and nucleotide analogues terminate the DNA chain; non-nucleoside inhibitors bind reverse transcriptase directly. Three: the provirus is permanent, so treatment is lifelong. Next, hepatitis B serology.

Sources

Numbers in the text, e.g. [1], point here
  1. Retrovirus. Wikipedia. en.wikipedia.org/wiki/Retrovirus
  2. HIV. Wikipedia. en.wikipedia.org/wiki/HIV
  3. OpenStax Microbiology, 6.2 The Viral Life Cycle. openstax.org/books/microbiology/pages/6-2-the-viral-life-cycle
  4. Europe PMC PMC13272464. europepmc.org/article/PMC/PMC13272464
  5. Europe PMC PMC13604433. europepmc.org/article/PMC/PMC13604433
  6. Europe PMC PMC12907452. europepmc.org/article/PMC/PMC12907452
  7. Europe PMC PMC13611976. europepmc.org/article/PMC/PMC13611976
  8. Europe PMC PMC3388302. europepmc.org/article/PMC/PMC3388302
  9. Europe PMC PMC12678287. europepmc.org/article/PMC/PMC12678287
  10. Maraviroc. Wikipedia. en.wikipedia.org/wiki/Maraviroc
  11. Enfuvirtide. Wikipedia. en.wikipedia.org/wiki/Enfuvirtide
  12. Reverse-transcriptase inhibitor. Wikipedia. en.wikipedia.org/wiki/Reverse-transcriptase_inhibitor
  13. Integrase inhibitor. Wikipedia. en.wikipedia.org/wiki/Integrase_inhibitor
  14. Protease inhibitor (pharmacology). Wikipedia. en.wikipedia.org/wiki/Protease_inhibitor_(pharmacology)
  15. Ritonavir. Wikipedia. en.wikipedia.org/wiki/Ritonavir
  16. Lenacapavir. Wikipedia. en.wikipedia.org/wiki/Lenacapavir

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined, resized): HIV, lymphocyte, cell membrane, antibody, syringe, nucleus, chromosome. NIAID NIH BioArt (public domain): pill, ribosome, hepatocyte. Health Icons (CC0): man. The CD4 and CCR5 receptors, enzyme sketches, chain-termination diagram, charts, question card, pocket card and all handwriting are drawn in code (original). No AI-generated teaching images.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-MICRO-010.

For exam study only, not medical advice. Read the medical disclaimer.

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