HIV: life cycle and principles of antiretroviral therapy
How HIV copies itself inside immune cells, and why treatment uses several drugs together, taken every day, for life.
HIV is a retrovirus that infects CD4 T cells and macrophages, writes its RNA into DNA and stitches that DNA into the host genome. Each step of its life cycle is a drug target. Antiretroviral therapy (ART) combines drugs from different classes to stop replication, let the immune system recover and prevent transmission. It does not cure the infection, because integrated provirus persists in resting cells.
The virus and its life cycle
HIV carries two copies of an RNA genome inside a protein core wrapped in an envelope taken from the host cell. Its genes code for structural proteins (gag), the enzymes reverse transcriptase, integrase and protease (pol), and the envelope glycoprotein (env). The cycle runs in a fixed order, and drug classes line up along it.
- Attachment and coreceptor binding: the envelope binds CD4, then CCR5 or CXCR4. CCR5 antagonists (maraviroc) and attachment or post-attachment inhibitors act here.
- Fusion: the viral and cell membranes merge; fusion inhibitors (enfuvirtide) block this.
- Reverse transcription: viral RNA is copied into double-stranded DNA. NRTIs act as faulty building blocks that end the chain; NNRTIs bind a pocket next to the active site.
- Integration: integrase inserts viral DNA into the host chromosome; integrase strand transfer inhibitors (dolutegravir, bictegravir, cabotegravir) block it.
- Assembly and budding: new viral proteins and RNA gather at the membrane; capsid inhibitors (lenacapavir) disturb the capsid at several steps.
- Maturation: HIV protease cuts long polyproteins into working parts; protease inhibitors leave the new particles immature and non-infectious.
How HIV causes disease
Untreated, HIV replicates continuously and destroys CD4 T cells faster than the body can replace them. Over years, CD4 counts fall and the person becomes vulnerable to opportunistic infections and cancers that define AIDS. WHO calls this stage advanced HIV disease and defines it by a low CD4 count or a severe clinical event; all young children with HIV are counted as having it. Once integrated, the provirus can lie silent in long-lived resting cells, a reservoir that ART cannot reach, which is why stopping treatment lets the virus rebound.
Why combinations: the resistance problem
Reverse transcriptase has no proofreading, and the body makes enormous numbers of virions each day. Because of this, an untreated person almost certainly already carries viruses with single mutations that weaken every individual drug. One drug alone selects those variants within weeks. Three active drugs, usually from at least two classes, make it very unlikely that one virus resists all of them at once. Standard first regimens pair two nucleos(t)ide reverse transcriptase inhibitors with a third agent, today most often an integrase inhibitor.
When to start and what to aim for
Large randomised trials showed clinical benefit from starting ART regardless of CD4 count, so guidelines now offer treatment to everyone with HIV as soon as possible after diagnosis. Pregnant women are started promptly to protect the baby. Success is measured with the plasma viral load (HIV RNA): in a person starting a first regimen, the expected result is an undetectable level within months. A viral load that rises again and stays up while the person is still on the regimen marks virological failure and usually means resistance, so the regimen is changed with the help of the treatment history and resistance testing.
Adherence, prevention and long-acting options
Daily adherence is the core of treatment. Even occasional missed doses allow replication, immune damage and resistance. Undetectable viral load also prevents transmission during pregnancy and birth. Antiretrovirals are used for prevention as well: pre-exposure prophylaxis (PrEP) with oral tenofovir-based regimens, a dapivirine vaginal ring, or long-acting injectable cabotegravir or lenacapavir, and post-exposure prophylaxis (PEP) after a risk event. Long-acting injectables help people who struggle with daily pills.
Safety checks and interactions
- HLA-B*5701 is screened before abacavir; carriers have a high risk of a dangerous hypersensitivity reaction and must not receive it.
- A tropism test is done before maraviroc, which only works on CCR5-using virus.
- IRIS: as immunity recovers, inflammation can flare against residual infections (for example tuberculosis or cryptococcus); autoimmune conditions such as Graves disease can appear months later.
- Ritonavir and cobicistat are used as pharmacokinetic boosters: they inhibit CYP3A and raise levels of other drugs, so interactions with many common medicines must be checked.
- Some antiretrovirals (tenofovir, lamivudine, emtricitabine) also suppress hepatitis B; stopping them in a coinfected person can trigger a hepatitis flare.
Test yourself
Think of the answer, then tap the question to see it.
Why is HIV never treated with a single antiretroviral drug?
Its error-prone reverse transcriptase means resistant variants already exist before treatment; one drug selects them quickly, while several active drugs together make simultaneous resistance very unlikely.
Which step of the HIV life cycle do integrase strand transfer inhibitors block, and what does that prevent?
They stop integrase from inserting viral DNA into the host chromosome, so the cell cannot become a permanent source of new virus.
What does Undetectable = Untransmittable mean?
A person with HIV whose ART keeps the viral load undetectable does not pass HIV to sexual partners.
Which test is required before starting maraviroc, and why?
A tropism test, because maraviroc only blocks the CCR5 coreceptor and does not stop virus that enters through CXCR4.
What is IRIS in a person who has just started ART?
Immune reconstitution inflammatory syndrome: as immunity recovers, it mounts an inflammatory response against residual opportunistic infections, which can look like worsening illness.
Example drugs
- Dolutegravir
- Bictegravir
- Tenofovir disoproxil
- Tenofovir alafenamide
- Lamivudine
- Emtricitabine
- Abacavir
- Maraviroc
- Enfuvirtide
- Ritonavir
- Cobicistat
- Cabotegravir
- Lenacapavir
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Treating HIV (U.S. Centers for Disease Control and Prevention, 2026); HIV and AIDS (World Health Organization, 2026); DailyMed - ABACAVIR tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.