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# Integrase strand transfer inhibitors (INSTIs)

They stop HIV DNA from being inserted into the cell's DNA. Dolutegravir is now the backbone of WHO-recommended treatment.

Updated 2026-11-01

## What they are

Integrase strand transfer inhibitors: dolutegravir, bictegravir, raltegravir and cabotegravir. They lower viral load quickly, are well tolerated, and the second-generation agents (dolutegravir, bictegravir) have a high genetic barrier. WHO recommends dolutegravir as the preferred first- and second-line treatment for all populations.

## Mechanism of action

Integrase trims the ends of viral DNA and then inserts it into the human chromosome (strand transfer). These drugs bind the two magnesium ions in the active site of the integrase-viral DNA complex (intasome) and block that step. Without integration, the virus cannot establish infection in the cell.

Target: HIV integrase (intasome), two-magnesium active site

## Key points

- Polyvalent cations (aluminium or magnesium antacids, calcium, iron) chelate them and reduce absorption: doses must be separated.
- Dolutegravir and bictegravir inhibit the OCT2 transporter: creatinine rises slightly without harming filtration, and metformin levels increase.
- Rifampicin (a UGT1A1 and CYP3A inducer) lowers their levels, a key point in tuberculosis co-infection.
- Weight gain with long-term dolutegravir use.
- Long-acting injectable cabotegravir is used for prevention (PrEP) and, with injectable rilpivirine, for treatment.

## Drugs in this class

- [**Dolutegravir** A high-barrier integrase inhibitor, the backbone of WHO's preferred treatment for all populations, including pregnant… HIV integrase (intasome)](https://durgical.com/en/pharmacology/dolutegravir/)
- [**Raltegravir** An integrase inhibitor that is very well tolerated with few interactions, though its genetic barrier is lower than… HIV integrase (intasome)](https://durgical.com/en/pharmacology/raltegravir/)
- [**Bictegravir** A second-generation integrase inhibitor sold only in a single tablet with emtricitabine and tenofovir alafenamide. HIV integrase (intasome)](https://durgical.com/en/pharmacology/bictegravir/)
- [**Cabotegravir** An integrase inhibitor available as a long-acting injection: it prevents HIV (PrEP) and, with rilpivirine, treats it… HIV integrase (intasome)](https://durgical.com/en/pharmacology/cabotegravir/)

## Others in the class

- Elvitegravir (with cobicistat)

## Test yourself

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

## Which step of the HIV life cycle do INSTIs block?

Strand transfer: insertion of viral DNA into the cell's DNA.

## Why can a magnesium antacid make an INSTI fail?

INSTIs bind metals; the antacid cation chelates them in the gut and greatly reduces absorption.

## Why does creatinine rise on dolutegravir without worse kidney function?

Dolutegravir inhibits the tubular OCT2 transporter and reduces creatinine secretion; glomerular filtration does not change.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 64 (McGraw Hill, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J05AJ) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [WHO recommends dolutegravir as preferred HIV treatment option in all populations](https://www.who.int/news/item/22-07-2019-who-recommends-dolutegravir-as-preferred-hiv-treatment-option-in-all-populations) (World Health Organization, 2019).

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