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Human Immunodeficiency Virus (HIV)

BASHH/BHIVA guidelines (see below for individual references).

NICE CKS HIV infection and AIDS. Last revised: Sep 2025.

Background Information

Definition

HIV is a chronic viral infection characterised by progressive immune system damage, primarily targeting CD4+ T lymphocytes, leading to impaired cell-mediated immunity.

Also see the Advanced HIV, AIDS, and HIV-Associated Conditions article.

Virology

HIV is a single-stranded, positive-sense RNA retrovirus [Ref]

  • Retroviruses are characterised by the presence of the enzyme reverse transcriptase, which enables conversion of viral RNA into DNA within the host cell

HIV life cycle: [Ref]

Step Description Key involved molecules
1. Attachment (binding) HIV attaches / bind to CD4+ T lymphocytes Viral gp120 binds CD4 receptor
2. Co-receptor binding After initial CD4 binding, gp120 changes shape to bind chemokine co-receptors Viral gp120 binds CCR5 or CXCR4 (chemokine co-receptor)
3. Fusion and entry Viral envelope fuses with host membrane → viral RNA enters host cytoplasm Viral gp41 mediates membrane fusion
4. Reverse transcription Viral reverse transcriptase enzyme converts viral RNA into double-stranded DNA Viral reverse transcriptase enzyme
5. Integration Viral DNA integrates into host genome Viral integrase enzyme
6. Transcription Host transcribes viral DNA into viral mRNA Host RNA polymerase
7. Translation Host translates viral mRNA into viral proteins Host ribosomes
8. Assembly Viral RNA and proteins assemble at host cell membrane Viral polyproteins
9. Budding and release Immature HIV virion buds from host cell, host membrane is used to form the viral envelope

Transmission

HIV can be transmitted from infected body fluids: [Ref1][Ref2][Ref3]

Body fluids that CAN transmit HIV Body fluids that CANNOT transmit HIV
  • Blood / blood products
  • Semen and pre-seminal fluid
  • Vaginal / cervical secretions
  • Rectal secretions
  • Any visibly bloody body fluid
  • Breast milk
  • Saliva (contains HIV inhibitors, infectious virus rarely detected)
  • Tears (very low viral concentration, contains local antimicrobial)
  • Sweat (not present)
  • Urine and faeces (no documented transmission)
  • Nasal secretions (no doccumented trasmission)

Important activities that can allow HIV transmission include:

Sexual activity (vaginal / anal / oral sex) Transmitted via mucosal membranes

Esp. in the presence of oral diseases (e.g. ulceration, gingivitis)

Vertical transmission From mother to child

During pregnancy, childbirth, or breastfeeding

Inoculation Contaminated needles (e.g. IVDU) / instruments / blood / blood products
Direct exposure of mucous membranes or open wounds to infected body fluids
Human bite that breaks the skin

Importantly, HIV is NOT transmitted by: [Ref]

Mode of contact Rationale
Social interactions (e.g. hugging, shaking hands) HIV does NOT penetrate intact skin
Sharing eating utensils, glasses, food, and drinks Saliva contains potent HIV inhibitors and only contains non-infectious viral components
Kissing
Toilet seats HIV does not survive well on environmental surfaces + intact skin barrier
Gym equipments
Mosquitoes HIV does not replicate in mosquitoes
Swimming pool and hot tubs Chlorine inactivates HIV, virus cannot survive in pool water

Risk Factors

The chance of HIV transmission depends on sexual practice:

  • Receptive anal sex > insertive anal sex > receptive vaginal sex > insertive vaginal sex
  • Vaginal sex has a lower risk, compared to anal sex

Other risk factors include:

  • MSM
  • Anal sex practice
  • Viral load (the higher the viral load, the more likely the transmission)
  • Concurrent STI
  • Unprotected sex, sex workers
  • IVDU
  • Occupational exposure (e.g. sharps and mucosal splash injuries)
  • High-risk sexual practice (e.g. chemsex)
  • People with a HIV +ve mother
  • Blood transfusions, transplants, or other invasive procedures in countries without rigorous HIV screening

Clinical Features

After initial exposure, HIV infection progresses through distinct stages:

Stage Clinical manifestation
Primary HIV infection / HIV seroconversion illness Occurs 2-4 weeks after the infection

Patients could be asymptomatic or present with flu-like symptoms:

  • Fever
  • Sore throat
  • Rash
  • Lymphadenopathy
  • Fatigue

The viral load is very high in this phase, the patient would be highly infectious.

Asymptomatic phase Follows resolution of the primary infection and may persist for several years

  • Most patients remain well and asymptomatic
  • The person remains infectious
  • HIV continues to replicate at lower levels, gradually weakening the immune system
Symptomatic phase Develops as the patient’s immune function declines

  • Opportunistic infections
  • Multi-system complications
Advanced HIV disease / AIDS Defined by:

  • CD4 cell count<200, or
  • Presence of AIDS-defining conditions

Also see the Advanced HIV, AIDS, and HIV-Associated Conditions article.

Reference

Investigation and Diagnosis

Indications for HIV Testing

HIV testing is recommended in:

  • People with features consistent with an HIV indicator condition
  • People with HIV +ve sexual partners
  • People attending the following services
    • Sexual health 
    • Addiction and substance misuse
    • Antenatal
    • Termination of pregnancy
    • Hepatitis B and C, TB and lymphoma
  • People commencing chemotherapy or immunosuppressive or immunomodulatory therapy
  • People belonging to groups at increased risk of exposure to HIV
    • MSM
    • Female sexual contacts of MSM
    • Black Africans
    • Current or prior injecting drug use
    • Sex workers
    • Prisoners
    • Trans women
    • From country with high diagnosed seroprevalence (>1%)
    • Sexual contact with anyone from a country with high diagnosed seroprevalence (>1%)
  • People accessing primary and secondary healthcare in areas of high and extremely high HIV seroprevalence (including emergency departments)

HIV Diagnostic Pathway

Initial screening test: 4th-generation combination assay (HIV p24 antigen + HIV antibody) with venous sampling ASAP after potential exposure

Action / interpretations:

+ve Screening test Immediately perform a confirmatory assay on a different sample (ideally, a fresh blood sample)

  • HIV can only be diagnosed if the screening test is +ve and the confirmatory assay is +ve
  • Do not diagnose HIV based on 1 +ve test
-ve Screening test Subsequent action depends on whether the testing is performed within the 45-day window period or not

  • <45 days post-exposure → repeat test at ≥45 days (only exclude HIV if the repeat test is also -ve)
  • ≥45 days post-exposure → no further test needed (HIV excluded)

See greenbox for rationale.

If results are +ve from self-tests, confirmatory laboratory testing is always required due to a small possibility of a false-positive result.

Rationale:

The 4th-generation combination assay has a window period of 45 days.

The window period is the time between HIV exposure and when the test can reliably detect infection:

  • <45 days post-exposure → test may be falsely negative → repeat testing required at ≥45 days
  • ≥45 days post-exposure → a negative test can reliably exclude HIV

Baseline Post-Diagnosis Investigations

The following tests are recommended at baseline (organised into the following 3 categories):

Category Tests
HIV-related tests
  • CD4+ T cell count
  • HIV-1/-2 status
  • HIV viral load
  • Drug resistance test
Infection screen
  • Hep A, Hep B, Hep C screen
  • STI screen
    • Chlamydia (NAAT)
    • Gonorrhoea (NAAT)
    • Syphilis (serology)
Routine bloods
  • FBC
  • Renal function
  • Liver function
  • Bone profile
  • Urinalysis

References

HIV Management – Antiretroviral Therapy (ART)

Indications and Timing

Treatment with ART should be started ASAP after the diagnosis is made, regardless of CD4 T cell count.

Choice of Drugs and Regimen

HIV is treated with antiretroviral therapy (ART), a treatment regimen typically comprised of 3 or more different antiretroviral drugs to overcome the risk of drug resistance.

HIV-1 (most cases in the UK)

There are two 1st line regimens:

Triple therapy (most commonly used) 2 NRTIs PLUS 1 integrase inhibitor

  • Tenofovir AF (NRTI) + emtricitabine (NRTI) + bictegravir (integrase inhibitor)
  • Tenofovir AF or DX (NRTI) + emtricitabine (NRTI) + dolutegravir (integrase inhibitor)
  • Abacavir (NRTI) + lamivudine (NRTI) + dolutegravir (integrase inhibitor)
Two-drug ART regimen
  • Lamivudine (NRTI) + dolutegravir (integrase inhibitor)
  • Strict criteria: no lamivudine resistance + RNA copies <500,000 + CD4 count >200 + no active hepatitis B

Pre-testing for HLA-B*57:01 is necessary before starting abacavir.

Patients who are HLA-B*57:01 positive must NOT receive abacavir, as they are at risk of a severe hypersensitivity reaction.

Tenofovir DX (disoproxil) is an older oral pro-drug, while tenofovir AF (alafenamide) is a newer oral pro-drug.

Tenofovir DX carries a higher risk of renal and bone toxicity than tenofovir AF.

HIV-2 (rare in the UK, endemic in West Africa)

HIV-2 has intrinsic resistance to all NNRTIs, therefore it is important to avoid them.

1st line: triple ART with 2 NRTI backbone and boosted protease inhibitor

  • Tenofovir / abacavir (NRTI) + lamivudine (NRTI) + boosted darunavir (protease inhibitor)

Ongoing Follow-up and Monitoring

  • Minimum yearly review
  • Aim for viral load of <50 copies/mL

References


HIV PrEP (pre-exposure prophylaxis)

HIV Testing in PrEP

3-monthly HIV testing should be routinely offered as part of monitoring for PrEP.

Indications

Main indications are:

  • Condomless receptive anal sex (MSM and trans-women)
  • Condomless sex with HIV +ve partner with VL >200 copies/mL
  • IVDU with shared equipment (not routinely recommended if effective needle-exchange or opioid substitution programmes exist)

Drugs and Regimen

1st line regimen (dual NRTI): tenofovir disoproxil + emtricitabine (300/200 fixed dose combo)

There are 2 main dosing regimens:

Dosing regimen Suitability Description
Daily PrEP All high-risk individuals One tablet daily → until 7 days after last exposure
On-demand PrEP Anal exposures ONLY 2+1+1 (2 tablets pre-sex → 1 tablet 24 hr post sex → 1 tablet 48 hr post sex)

  • Must plan ahead, as 1 tablet needs to be taken BEFORE the exposure

If multiple-day exposure → 1 tablet daily until 48 hr after last exposure

It is important to ensure the person is HIV -ve before taking PrEP. As PrEP regimens contain only 2 drugs, if the patient is already HIV +ve, using only 2 agents risks sub-therapeutic suppression (allowing the virus to replicate) and drug resistance.

Reference

HIV PEP (post-exposure prophylaxis)

Indications

Indications for PEP are categorised and presented below:

Type of exposure Indications
Sexual exposure If index HIV +ve

  • Anal sex (receptive / insertive)
  • Receptive vaginal sex
  • Insertive vaginal sex

If the index HIV status is unknown

  • Receptive anal sex
  • Insertive anal sex
Occupational exposure Only indicated if index HIV +ve AND any of the following:

  • Sharps injury
  • Mucosal splash injury
  • Sharing injecting equipment

Key points about the risk of transmission:

  • Receptive sex carries a higher risk than insertive sex.
  • Anal sex carries a higher risk than vaginal sex.

BASHH/BHIVA – Summary table of PEP prescribing recommendations

Baseline Tests

Baseline tests required before initiating PEP:

  • HIV-1 Ag/Ab
  • Serum creatinine and eGFR
  • Alanine transaminase

 

  • Hepatitis B serology – if not vaccinated or with documented HepBsAb >10 IU
  • Chlamydia, gonorrhoea, syphilis testing – if from sexual exposure
  • Hepatitis C screening – if from occupational exposure OR those at risk from sexual exposure (e.g. MSM)

Drugs and Regimen

1st line regimen: 3 drug tenofovir (NRTI) + emtricitabine (NRTI) + raltegravir (integrase inhibitor)

Timings:

  • Start PEP within 72 hours (ideally <24 hours, guidelines say not to initiate PEP if >72 hours)
  • Duration of PEP: 28 days (4 weeks)

Follow Up

Repeat HIV testing at 45 days after completion of the 28‑day PEP course (not 45 days after exposure).

Reference

HIV in Pregnancy

See the HIV and Pregnancy article.

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