Anti retroviral therapy in UK
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antiretroviral therapy UK guidelines 2025 BHIVA NHS
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Anti retroviral therapy in UK
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BHIVA 2025 antiretroviral therapy guidelines UK preferred regimens
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BHIVA 2025 interim update ART guidelines first line regimens dolutegravir bictegravir cabotegravir lenacapavir
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BHIVA 2025 ART guidelines monitoring viral load CD4 switching virological failure UK NHS
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site:i-base.info BHIVA 2025 interim update ART adults cabotegravir rilpivirine long acting injectable
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Now I have comprehensive information from both the medical library and current BHIVA guidelines. Let me compile the full answer.
Antiretroviral Therapy (ART) in the UK
Overview
ART is the cornerstone of HIV management in the UK. The British HIV Association (BHIVA) sets clinical guidelines, most recently updated in the 2022 guidelines with a 2025 interim update (published 1 October 2025). NHS England commissions and funds ART, with prescribing guidance also set by the National HIV ARV Prescribing Toolkit (v2.1, August 2025).
The primary goals of ART are:
- Suppress HIV RNA to undetectable levels (<50 copies/mL)
- Restore/preserve immune function (CD4 count recovery)
- Prevent AIDS-defining illnesses and onward transmission
- Minimise drug toxicity and support long-term adherence
When to Start ART
ART should be initiated in all people living with HIV, regardless of CD4 count, including those with counts >500 cells/mm³. The only situations where a brief delay may be appropriate are:
- Cryptococcal meningitis — delay ART by several weeks (risk of immune reconstitution inflammatory syndrome/IRIS)
- Tuberculosis — delay ART by 2–8 weeks after starting TB therapy (except in patients with CD4 <50)
Drug Classes Available
| Class | Examples |
|---|---|
| Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) | Tenofovir alafenamide (TAF), Tenofovir disoproxil fumarate (TDF), Emtricitabine (FTC), Lamivudine (3TC) |
| Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) | Rilpivirine, Doravirine, Efavirenz |
| Integrase Strand Transfer Inhibitors (INSTIs) | Dolutegravir (DTG), Bictegravir (BIC), Cabotegravir (CAB), Raltegravir, Elvitegravir |
| Protease Inhibitors (PIs) | Darunavir (boosted with ritonavir or cobicistat) |
| Capsid Inhibitors | Lenacapavir |
| Fusion Inhibitors | Enfuvirtide |
| CCR5 Antagonists | Maraviroc |
Preferred First-Line Regimens (BHIVA 2025)
BHIVA recommends INSTI-based regimens as first-line treatment. The 2025 interim update made important changes:
Triple therapy (3-drug)
- Bictegravir/TAF/FTC (co-formulated as Biktarvy®) — once daily
- Dolutegravir + TAF or TDF + FTC or 3TC — once daily
Dual therapy (2-drug) — major 2025 update
- Dolutegravir/Lamivudine (DTG/3TC) (co-formulated as Dovato®) is now recommended at any CD4 count, removing the previous caution against use at viral load >500,000 copies/mL
- Not recommended in: hepatitis B co-infection, 3TC resistance present, or if resistance testing unavailable
Protease inhibitor-based (for specific indications)
- Boosted Darunavir + tenofovir + FTC/3TC — used when high-barrier resistance cover is needed (e.g., very high viral load >500,000 copies/mL, or where dolutegravir/bictegravir not possible)
Abacavir (ABC): 2025 update
- Abacavir has been removed from preferred first-line ART (BHIVA 2025)
- Proactive switching away from abacavir is now recommended — e.g., switching DTG/ABC/3TC → dual DTG/3TC
- Still requires HLA-B*5701 testing before use if clinically needed
Long-Acting Injectable ART (LA-ART)
A major 2025 update introduced expanded options for injectable ART:
- Cabotegravir + Rilpivirine LA (CAB/RPV-LA) (Vocabria®/Rekambys®): Given as intramuscular injections every 2 months in clinic. Approved for switching from stable oral ART with undetectable viral load
- New 2025 update: CAB/RPV-LA can now be used off-label for some people with detectable viral load on oral ART, when there is a risk of HIV progression (e.g., adherence challenges)
- Lenacapavir (Sunlenca®): A capsid inhibitor given as subcutaneous injection every 6 months, now added as an option for multi-drug resistant (MDR) HIV
Monitoring on ART
| Parameter | Frequency |
|---|---|
| HIV viral load | At baseline, 4 weeks after starting/switching, then every 3–6 months once stable |
| CD4 count | At baseline; less frequent once suppressed and CD4 >350 |
| Renal function (eGFR, phosphate) | If on TDF or TAF; at baseline and annually |
| Lipid profile | Baseline and annually |
| Hepatitis B surface antigen / serology | Before starting any regimen (crucial before TAF/TDF/3TC/FTC) |
| HLA-B*5701 | Before abacavir use |
| Drug resistance testing | Before starting ART; at virological failure |
Switching ART
Reasons to switch include:
- Virological failure (HIV RNA >200 copies/mL on two consecutive occasions)
- Toxicity/tolerability issues
- Simplification (e.g., switching to dual therapy or LA injectable)
- Drug interactions
- Pregnancy planning (avoid DTG peri-conception if possible — neural tube defect risk)
After any switch, viral load should be checked at 2 weeks post-switch, then followed per standard schedule.
Virological Failure
Defined as failure to achieve undetectable viral load, or confirmed rebound above 200 copies/mL. Key steps:
- Assess and address adherence first
- Perform resistance genotyping
- Switch to a regimen containing at least two, ideally three, fully active agents
- High-barrier drugs (DTG, BIC, boosted DRV) preferred in salvage settings
- Lenacapavir is now a BHIVA-recommended option for MDR HIV
Special Populations
| Group | Key Considerations |
|---|---|
| HIV/TB co-infection | Avoid rifampicin with most INSTIs; use DTG with dose adjustment (50mg BD), or boosted PIs are usually avoided |
| HIV/Hepatitis B co-infection | Must include TDF or TAF + FTC/3TC in regimen (active against HBV); stopping these risks HBV flare |
| HIV/Hepatitis C co-infection | Check drug-drug interactions between DAAs and ART |
| Pregnancy | Continue or initiate ART; DTG preferred but counsel about low neural tube defect risk; RPV not recommended in pregnancy |
| HIV-2 | NNRTIs, enfuvirtide, and fostemsavir are not active against HIV-2; use INSTI-based or PI-based regimens |
| Older adults and renal impairment | Prefer TAF over TDF (lower renal/bone toxicity); TAF generally safe to CrCl >15–30 mL/min |
UK-Specific Access & Prescribing
- ART is fully funded by NHS England through commissioned HIV services
- The BHIVA National HIV ARV Prescribing Toolkit (v2.1, August 2025) governs prescribing, including Blueteq approval for certain higher-cost regimens
- Regimens no longer requiring Blueteq pre-approval (2025): Rezolsta®, Symtuza®, Eviplera®
- HIV services in the UK are largely delivered through specialist HIV clinics, usually in GUM/sexual health or infectious disease settings
Key Sources:
- BHIVA 2022 ART Guidelines (2025 Interim Update)
- HIV i-Base: BHIVA 2025 interim update summary
- BHIVA National ARV Prescribing Toolkit v2.1 (Aug 2025)
- Harrison's Principles of Internal Medicine 22E (2025), Chapter 208
Is it NRTI + NNRTI ?
No. The standard backbone for first-line ART is 2 NRTIs + an INSTI (integrase inhibitor), not an NNRTI.
Current BHIVA-Preferred First-Line Regimens (2025)
| Backbone | Third Agent | Example |
|---|---|---|
| TAF/FTC or TDF/FTC | INSTI: Bictegravir | Biktarvy® (BIC/TAF/FTC) |
| TAF/FTC or TDF/FTC | INSTI: Dolutegravir | DTG + TAF/FTC |
| — (dual therapy) | INSTI: Dolutegravir + 3TC | Dovato® |
INSTIs (especially dolutegravir and bictegravir) have replaced NNRTIs as the preferred third drug because they have:
- Higher barrier to resistance — require multiple mutations to develop resistance
- Better tolerability
- Fewer drug-drug interactions than older NNRTIs (e.g., efavirenz)
- Efficacy across all baseline viral loads
Where NNRTIs Still Feature
NNRTIs are not first-line preferred in BHIVA guidelines but may still be used in specific situations:
- Rilpivirine — used in the long-acting injectable CAB/RPV-LA (cabotegravir + rilpivirine), given every 2 months as a maintenance switch in suppressed patients
- Doravirine — an option in certain circumstances (e.g., INSTI intolerance)
- Efavirenz — largely historical/legacy use; still used in resource-limited settings globally (WHO)
- Etravirine — second/third-line salvage in NNRTI-experienced patients
Why the Shift Away from NNRTIs?
- Low genetic barrier to resistance (single mutation can cause full resistance — e.g., K103N for efavirenz/nevirapine)
- CNS side effects with efavirenz (vivid dreams, dizziness)
- Drug interactions via CYP450 induction/inhibition
- Rilpivirine contraindicated if baseline viral load >100,000 copies/mL or with PPIs
So in summary: 2 NRTIs + INSTI is the current standard. NNRTI-based regimens (2 NRTIs + NNRTI) are no longer preferred first-line in the UK.
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