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ID: HIV, viral hepatitis and blood-borne viruses

🧬 HIV, viral hepatitis and blood-borne viruses -page 3 of the Infectious Diseases chapter. HIV is now a long-term condition: with early diagnosis and treatment, people with HIV have a near-normal life expectancy and cannot pass it on sexually when their viral load is undetectable. Hepatitis C is curable with 8–12 weeks of tablets, and hepatitis B is preventable by vaccination and controllable with treatment. The biggest problem is late diagnosis -so offer tests widely.
Your four questions for every patient: Should this person be tested for HIV, hepatitis B and hepatitis C? If positive, how advanced is the infection (CD4, viral load, liver fibrosis)? What treatment do they need, and what will it interact with? How do we protect partners, babies and contacts?


HIV Basics
  • HIV (human immunodeficiency virus) -a retrovirus that infects CD4 T cells, copies its RNA into DNA (reverse transcriptase) and inserts it into the cell's DNA (integrase). Without treatment, CD4 cells fall over years → AIDS.
  • Transmission -sex (anal sex carries the highest sexual risk), sharing injecting equipment, mother to baby (pregnancy, birth, breastfeeding), contaminated blood and needlestick injuries. Not spread by kissing, sharing utensils or everyday contact.
  • Natural history without treatment:
    • Primary infection (2–6 weeks after exposure) -flu-like or glandular fever-like illness in many; very high viral load (highly infectious).
    • Chronic phase (often years with few symptoms) -gradual CD4 loss; minor conditions (shingles, seborrhoeic dermatitis, oral thrush).
    • AIDS -CD4 under 200 cells/microlitre or an AIDS-defining illness (opportunistic infections, certain cancers).
  • Two key blood tests:
    • CD4 count (normal about 500–1,500 cells/microlitre) -shows immune damage and the risk of opportunistic infections.
    • Viral load (HIV RNA copies/mL) -shows how active the virus is and whether treatment is working (target -undetectable, under 50 copies/mL).
  • UK picture -most people with HIV are diagnosed and on effective treatment, but a large proportion are still diagnosed late (CD4 under 350), which carries higher risk of illness and death.
  • Living with HIV -with treatment, life expectancy is close to normal; long-term issues include cardiovascular disease, kidney and bone health, mental health, stigma and ageing.
Testing for HIV
  • Any doctor can offer an HIV test -verbal consent is enough; no specialist counselling is needed (explain the benefits and how results will be given).
  • Who to test (BHIVA/BASHH and NICE NG60):
    • Anyone with an indicator condition or symptoms suggesting HIV (see below).
    • Everyone attending sexual health and drug services, all pregnant women, people with TB, hepatitis B or C, or lymphoma.
    • Higher-risk groups -men who have sex with men, people from countries with high HIV prevalence, people who inject drugs, sex workers, sexual partners of people with HIV.
    • In areas of high HIV prevalence -routine ("opt-out") testing for all adults having blood tests in emergency departments, on hospital admission and at GP registration.
  • Tests:
    • Fourth-generation test (HIV antibody plus p24 antigen) -the standard lab test; detects most infections by 4 weeks after exposure; a negative result 45 days after the last exposure excludes HIV.
    • Point-of-care and self-tests (antibody-based) -longer window period (up to about 90 days); confirm positives in the lab.
    • HIV viral load -very high in primary infection; used for monitoring, not usually for screening.
  • Giving a positive result -face to face where possible, with prompt referral (within 2 weeks -sooner if unwell) to an HIV service; partner notification (through the HIV or sexual health team); reassure about treatment and outlook.
  • Missed opportunities -many people diagnosed late had seen healthcare professionals with indicator conditions in the years before; if in doubt, offer a test.
Primary HIV Infection
  • Timing -2–6 weeks after exposure; symptoms in most (though often mild or missed).
  • Features -fever, sore throat, maculopapular rash (trunk), mouth ulcers, lymphadenopathy, muscle and joint pain, headache, diarrhoea; sometimes aseptic meningitis, Guillain–Barré syndrome or facial palsy.
  • Blood tests -lymphopenia (or atypical lymphocytes), low platelets, raised liver enzymes.
  • "Glandular fever-like illness" -always consider primary HIV (and test) in someone with a negative EBV test, a rash or mouth ulcers, or recent risk.
  • Testing -a fourth-generation test may be negative very early; the viral load is very high -test both and repeat if suspicion remains.
  • Why it matters -people are most infectious at this stage; starting ART early protects the immune system and partners.
Indicator Conditions -When to Think of HIV
SystemAIDS-defining conditionsOther indicator conditions -offer a test
RespiratoryPneumocystis pneumonia, TB, recurrent bacterial pneumoniaCommunity-acquired pneumonia, aspergillosis
NeurologyCerebral toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, PML, HIV encephalopathyAseptic meningitis or encephalitis, unexplained peripheral neuropathy, Guillain–Barré, dementia or cognitive problems in younger people, space-occupying lesion
Skin and mouthKaposi's sarcomaSevere or recalcitrant seborrhoeic dermatitis or psoriasis, shingles (especially in younger people or several dermatomes), oral candida, oral hairy leukoplakia, multiple warts or molluscum
GI and liverOesophageal candidiasis, cryptosporidiosis (chronic), CMV colitisUnexplained chronic diarrhoea, weight loss, hepatitis B or C, salmonellosis
Blood and cancerNon-Hodgkin's lymphoma, invasive cervical cancerUnexplained low platelets, neutrophils or lymphocytes, Hodgkin's lymphoma, anal cancer and dysplasia, lung cancer, unexplained lymphadenopathy
EyesCMV retinitisUnexplained retinal disease, uveitis
GeneralHIV wasting syndromeMononucleosis-like illness, pyrexia of unknown origin, any STI, unexplained weight loss
Kidney-Unexplained CKD or nephropathy
Opportunistic Infections and Cancers
ConditionUsual CD4Features and diagnosisTreatment
TBAnyOften extrapulmonary or disseminated at low CD4; chest X-ray may be atypicalStandard TB drugs (rifampicin interactions with ART -specialist)
Pneumocystis pneumonia (PCP)Under 200Dry cough, breathlessness over weeks, desaturation on exercise; chest X-ray -bilateral perihilar haziness (can be normal); pneumothorax; induced sputum or bronchoscopy PCRHigh-dose co-trimoxazole for 21 days plus steroids if PaO2 under 9.3 kPa
Oesophageal candidiasisUnder 200Painful swallowing, oral thrushFluconazole
Cerebral toxoplasmosisUnder 100Headache, fever, focal signs, seizures; multiple ring-enhancing lesions (often basal ganglia); Toxoplasma IgG usually positivePyrimethamine plus sulfadiazine plus folinic acid
Primary CNS lymphomaUnder 100Usually a single lesion; EBV DNA in CSFSpecialist oncology; ART
Cryptococcal meningitisUnder 100Subacute headache, fever, confusion; very high CSF opening pressure; cryptococcal antigen in blood and CSFLiposomal amphotericin plus flucytosine, then fluconazole; repeated LPs for pressure; delay ART about 4–6 weeks
CMV retinitisUnder 50Floaters, blurred vision, field loss; haemorrhages and white exudates on the retinaGanciclovir or valganciclovir; urgent ophthalmology
Mycobacterium avium complexUnder 50Fever, sweats, weight loss, diarrhoea, anaemia, raised ALPClarithromycin plus ethambutol
PML (JC virus)LowProgressive weakness, speech, vision or cognitive problems; white matter lesions on MRI without enhancementNo specific treatment -ART
Kaposi's sarcoma (HHV-8)Any (more at low CD4)Purple skin, mouth, lung or gut lesionsART ± chemotherapy
  • Prophylaxis -co-trimoxazole when CD4 is under 200 (prevents PCP and toxoplasmosis) until CD4 recovers on ART; screen for latent TB and cryptococcal antigen (CD4 under 100) in at-risk patients.
  • Vaccines -pneumococcal, influenza, hepatitis A and B, HPV, COVID-19, shingles (non-live); avoid live vaccines (e.g. yellow fever, MMR) when CD4 is under 200.
Antiretroviral Therapy
  • Offer ART to everyone with HIV, whatever the CD4 count, as soon as possible (often the same week as diagnosis) -benefits the person and stops transmission.
  • Usual regimen -three drugs: two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase inhibitor; often a single daily tablet. Two-drug regimens (dolutegravir plus lamivudine) are used in selected people (no hepatitis B, no resistance). Long-acting injections (cabotegravir plus rilpivirine every 2 months) are an option for people already suppressed.
ClassExamplesKey side effects and cautions
NRTIsTenofovir (disoproxil or alafenamide), emtricitabine, lamivudine, abacavirTenofovir disoproxil -kidney tubular damage (Fanconi), bone loss (alafenamide less so); tenofovir, emtricitabine and lamivudine also treat hepatitis B (stopping can cause a hepatitis flare); abacavir -severe hypersensitivity in people with HLA-B*57:01 (test first), possible cardiovascular risk
Integrase inhibitorsDolutegravir, bictegravir, raltegravir, cabotegravirWell tolerated; insomnia, headache, weight gain; dolutegravir and bictegravir raise creatinine slightly (block its secretion -not true kidney damage); absorption reduced by antacids, calcium, iron, magnesium -separate doses
NNRTIsEfavirenz, rilpivirine, doravirineEfavirenz -vivid dreams, dizziness, low mood; rilpivirine -take with food; don't use with PPIs
Protease inhibitors (boosted)Darunavir with ritonavir or cobicistatGI upset, raised lipids; the boosters (ritonavir, cobicistat) are strong CYP3A4 inhibitors -many interactions
  • Monitoring -viral load (should become undetectable within about 3–6 months, then checked every 6–12 months), CD4 count, kidney function and urine protein, liver tests, lipids, bone health and cardiovascular risk; resistance testing before starting and if treatment fails.
  • Adherence is essential -missed doses allow resistance; support mental health, housing, drug and alcohol problems, and stigma.
  • Never stop ART in hospital without HIV team advice -if the patient can't take oral medicines, contact the HIV team or pharmacy (liquid forms, NG options).
Drug Interactions in HIV
  • Always check before prescribing anything to someone on ART -use the Liverpool HIV drug interaction checker (including over-the-counter, herbal and recreational drugs).
  • Boosted regimens (ritonavir or cobicistat) -strong CYP3A4 inhibition:
    • Simvastatin -contraindicated (rhabdomyolysis); use low-dose atorvastatin, rosuvastatin or pravastatin with advice.
    • Inhaled and nasal fluticasone and budesonide, and steroid joint injections (triamcinolone) -Cushing's syndrome and adrenal suppression; use beclometasone or alternatives.
    • Amiodarone, some DOACs, oral midazolam, sildenafil (raised levels), ergot drugs, some antipsychotics and antiseizure drugs, colchicine.
  • Enzyme inducers lower ART levels (treatment failure and resistance) -rifampicin (TB -needs specialist regimen changes), carbamazepine, phenytoin, St John's wort.
  • Absorption -PPIs and H2 blockers reduce rilpivirine (and atazanavir); antacids, calcium, iron and magnesium reduce integrase inhibitor absorption.
  • Contraception -some ART reduces hormonal contraceptive effect (efavirenz, boosted regimens) -check; levonorgestrel emergency contraception needs a double dose with enzyme inducers (or use a copper IUD).
  • Recreational drugs -boosters raise levels of MDMA, ketamine, GHB and some opioids (dangerous toxicity).
Starting ART and IRIS
  • Immune reconstitution inflammatory syndrome (IRIS) -as the immune system recovers on ART, it attacks infections that were present, causing a paradoxical worsening (fever, enlarging lymph nodes, worsening chest or brain lesions) usually in the first weeks to months.
  • Most common with TB, cryptococcal meningitis, MAC, CMV and PML; higher risk with very low CD4.
  • Timing of ART with opportunistic infections:
    • Most OIs (e.g. PCP) -start ART within about 2 weeks.
    • TB -start within 2 weeks if CD4 is under 50, otherwise within about 8 weeks; TB meningitis -specialist decision (higher risk).
    • Cryptococcal meningitis -delay ART for about 4–6 weeks (early ART increases deaths).
  • Management of IRIS -exclude new infection, drug reaction and treatment failure; usually continue ART; NSAIDs or steroids for significant IRIS (e.g. TB-IRIS).
Preventing HIV -PrEP, PEP and U=U
  • U=U (Undetectable = Untransmittable) -a person with HIV on ART with a viral load that has been undetectable for at least 6 months cannot pass HIV on through sex. This is one of the most powerful messages for reducing stigma and transmission.
  • Pre-exposure prophylaxis (PrEP) -HIV-negative people at risk take tenofovir disoproxil–emtricitabine:
    • Daily, or "event-based" dosing (for anal sex between men only).
    • Free through NHS sexual health clinics; requires a negative HIV test, kidney function monitoring, hepatitis B status and regular STI testing.
    • Very effective when taken correctly; doesn't protect against other STIs.
  • Post-exposure prophylaxis (PEP) after sexual or occupational exposure to HIV:
    • Start as soon as possible -ideally within 24 hours, and no later than 72 hours; continue for 28 days.
    • Usual regimen -tenofovir disoproxil–emtricitabine plus an integrase inhibitor (e.g. raltegravir).
    • Not usually needed if the source has HIV with an undetectable viral load (for sexual exposure).
    • Available from sexual health clinics and emergency departments; follow-up HIV testing.
  • Other prevention -condoms, needle and syringe programmes, opioid substitution therapy, testing and treating partners, antenatal screening.
HIV in Pregnancy
  • All pregnant women are offered HIV testing (and hepatitis B and syphilis screening) at booking; repeat testing later in pregnancy if at continued risk.
  • ART throughout pregnancy -continue effective regimens; start as soon as possible if newly diagnosed (dolutegravir-based regimens are recommended).
  • Delivery -planned vaginal birth if the viral load is under 50 copies/mL at 36 weeks; caesarean section is recommended if the viral load is high (e.g. over 400 copies/mL); IV zidovudine during labour in some situations.
  • Baby -antiretroviral post-exposure prophylaxis for 2–4 weeks; HIV testing over the first months (PCR -maternal antibodies cross the placenta).
  • Infant feeding -formula feeding removes the risk of transmission and is advised in the UK; women with a sustained undetectable viral load who choose to breastfeed should be supported with close monitoring (BHIVA).
  • With good care, the transmission rate in the UK is under 0.3%.
Viral Hepatitis at a Glance
VirusSpreadIncubationChronic infection?Vaccine?Treatment
A (RNA)Faecal–oral (food, water, shellfish, sexual)2–6 weeksNoYesSupportive
B (DNA)Blood, sex, mother to baby1–6 monthsYes -about 90% of infected newborns, about 5% of adultsYesTenofovir, entecavir (suppression); peginterferon
C (RNA)Blood (injecting drug use most), less often sex and mother to baby2 weeks–6 monthsYes -about 75%NoDirect-acting antivirals -over 95% cure
D (RNA)Blood, sex -only with hepatitis BVariesYes (worse hepatitis B)Hepatitis B vaccine protectsBulevirtide (specialist)
E (RNA)Undercooked pork and game (UK); contaminated water (abroad)2–8 weeksOnly in immunosuppressed peopleNot in the UKSupportive; ribavirin if chronic
  • Acute hepatitis features -tiredness, nausea, loss of appetite, right upper quadrant discomfort, then jaundice, dark urine and pale stools; ALT often in the thousands; many infections (especially in children, and hepatitis C) cause no symptoms.
  • Acute liver failure warning signs -rising INR, confusion (encephalopathy), hypoglycaemia -discuss urgently with a liver unit.
  • Other causes of hepatitis to consider -EBV, CMV, HSV (severe in pregnancy and immunosuppression), drugs (paracetamol), alcohol, autoimmune hepatitis, ischaemia, Wilson's disease.
Hepatitis A
  • Spread -faecal–oral: contaminated food and water, shellfish, travel to areas where it is common, outbreaks among men who have sex with men and people who inject drugs, household contacts.
  • Illness -usually mild in children (often no symptoms); adults often have jaundice for several weeks; more severe in older people and those with chronic liver disease; never becomes chronic; lifelong immunity after infection.
  • Diagnosis -hepatitis A IgM antibody.
  • Management -supportive; avoid alcohol and liver-toxic drugs; monitor INR; notify; exclude from work or school for 7 days after the onset of jaundice (or symptoms); good hand hygiene.
  • Prevention -vaccination for travellers, men who have sex with men, people who inject drugs, people with chronic liver disease, haemophilia, some occupations; post-exposure vaccine for contacts within 14 days (with immunoglobulin for some higher-risk contacts -UKHSA).
Hepatitis B
  • Spread -mother to baby (the main route worldwide), sex, blood (injecting, needlestick, medical procedures abroad, tattoos), household contact (shared razors and toothbrushes); highly infectious (much more than HIV).
  • Who is at risk -people born in countries with high prevalence (Asia, Africa, Eastern Europe), people who inject drugs, men who have sex with men, sex workers, household and sexual contacts of people with hepatitis B, people on dialysis, prisoners.
  • Acute infection -often no symptoms, or acute hepatitis with jaundice; rarely acute liver failure.
  • Chronic infection (HBsAg positive for over 6 months) -risk depends on age at infection: about 90% of infected newborns but under 5% of infected adults develop chronic hepatitis B.
  • Phases of chronic infection (vary over time):
    • HBeAg-positive chronic infection -very high viral load, normal ALT, little liver damage (often young people infected at birth).
    • HBeAg-positive chronic hepatitis -high viral load, raised ALT, active liver damage.
    • HBeAg-negative chronic infection ("inactive carrier") -low viral load, normal ALT.
    • HBeAg-negative chronic hepatitis -fluctuating viral load and ALT, progressive damage.
  • Complications -cirrhosis, hepatocellular carcinoma (can occur without cirrhosis -surveillance with 6-monthly ultrasound in cirrhosis and some high-risk groups), extrahepatic disease (polyarteritis nodosa, membranous glomerulonephritis).
  • Reactivation -hepatitis B can flare (sometimes fatally) when people are given chemotherapy, rituximab and other B-cell drugs, high-dose steroids, biologics, JAK inhibitors, or hepatitis C treatment -test HBsAg and anti-HBc before these treatments.
Hepatitis B Serology
MarkerMeaning
HBsAg (surface antigen)Current infection (acute or chronic); positive for over 6 months = chronic
Anti-HBs (surface antibody)Immunity -from vaccination (anti-HBs alone) or past infection (with anti-HBc)
Anti-HBc IgM (core antibody)Recent (acute) infection (can rise in flares of chronic infection)
Anti-HBc total / IgGExposure at some time -past (cleared) or current infection; not produced by vaccination
HBeAgHigh viral replication and high infectivity
Anti-HBeLower replication (but HBeAg-negative hepatitis can still be active)
HBV DNA (viral load)Amount of virus -guides treatment and pregnancy management
HBsAgAnti-HBcAnti-HBsInterpretation
NegativeNegativeNegativeNever infected, not immune -offer vaccination if at risk
NegativeNegativePositiveImmune from vaccination
NegativePositivePositivePast infection, now immune (reactivation risk with strong immunosuppression)
PositivePositive (IgM)NegativeAcute infection
PositivePositive (IgG)NegativeChronic infection (if over 6 months)
NegativePositiveNegativePast infection with waning anti-HBs, "occult" infection, or false positive -check HBV DNA; reactivation risk
Treating and Preventing Hepatitis B
  • Everyone with chronic hepatitis B needs specialist assessment -viral load, ALT, HBeAg, fibrosis assessment (FibroScan), HCC risk, and testing for hepatitis D, hepatitis C and HIV; vaccinate against hepatitis A.
  • Treatment (NICE CG165, EASL) -for active hepatitis or significant fibrosis, cirrhosis, family history of HCC, and other situations:
    • Tenofovir (disoproxil or alafenamide) or entecavir -oral, usually long-term; suppress the virus and reduce cirrhosis and cancer risk; rarely clear HBsAg; stopping can cause severe flares.
    • Peginterferon alfa -a fixed course of injections for selected patients (flu-like symptoms, depression, low blood counts, thyroid problems).
  • Prophylaxis before immunosuppression -antiviral (e.g. entecavir or tenofovir) if HBsAg positive, or anti-HBc positive before rituximab and similar high-risk treatments, continued for months afterwards.
  • Vaccination:
    • Routine infant vaccination in the UK (part of the 6-in-1 vaccine).
    • At-risk adults -healthcare workers (check anti-HBs after the course), people who inject drugs, men who have sex with men, sex workers, household and sexual contacts, dialysis patients, chronic liver and kidney disease, prisoners, some travellers.
    • Post-exposure -accelerated vaccine course ± hepatitis B immunoglobulin (HBIG) depending on source and recipient status.
  • Pregnancy:
    • All pregnant women are screened; women with high viral loads are offered tenofovir in the third trimester to reduce transmission.
    • Babies of HBsAg-positive mothers -hepatitis B vaccine within 24 hours of birth (plus HBIG if the mother is highly infectious), further doses at 4, 8, 12 weeks and 1 year, and a blood test at 12 months to confirm protection.
    • Breastfeeding is safe when the baby is vaccinated.
Hepatitis D
  • Hepatitis D (delta) -a defective virus that can only infect people who also have hepatitis B (it needs HBsAg).
  • Co-infection (B and D at the same time) -more severe acute hepatitis; superinfection (D on top of chronic B) -the most severe form of chronic viral hepatitis, with rapid progression to cirrhosis.
  • Higher prevalence -Eastern Europe, Mediterranean, Central Asia, parts of Africa, people who inject drugs.
  • Test all HBsAg-positive people for anti-HDV antibody (and HDV RNA if positive).
  • Treatment -specialist: bulevirtide (blocks viral entry into liver cells), peginterferon; prevention -hepatitis B vaccination.
Hepatitis C
  • Spread -mainly blood: injecting drug use (most UK infections), blood transfusion before 1991, medical and dental treatment and tattoos in countries with poor infection control; sexual spread mainly among men who have sex with men (especially with HIV); mother to baby (about 5%).
  • Natural history -acute infection is usually silent; about 75% become chronic; cirrhosis in about 20–30% over 20–30 years (faster with alcohol, HIV, obesity, older age), then liver cancer and liver failure.
  • Extrahepatic problems -cryoglobulinaemia (vasculitic rash, neuropathy, kidney disease), membranoproliferative glomerulonephritis, porphyria cutanea tarda, lichen planus, type 2 diabetes, B-cell lymphoma, fatigue and depression.
  • Testing:
    • HCV antibody -shows exposure at some time (stays positive after cure or spontaneous clearance).
    • HCV RNA (PCR) -confirms current infection; used to test for re-infection after cure (no lasting immunity).
    • Many labs now test RNA automatically on antibody-positive samples ("reflex testing"); dried blood spot tests are used in drug services.
  • Treatment -direct-acting antivirals (DAAs) for everyone with current infection:
    • Pangenotypic tablets for 8–12 weeks (e.g. sofosbuvir–velpatasvir, glecaprevir–pibrentasvir) -over 95% cure with few side effects.
    • Cure = undetectable HCV RNA 12 weeks after finishing (sustained virological response, SVR12).
    • Interactions -sofosbuvir with amiodarone (severe bradycardia -avoid), PPIs and antacids (reduce some DAAs), enzyme inducers (carbamazepine, phenytoin, rifampicin, St John's wort -contraindicated), statins, ethinylestradiol with some regimens (liver enzyme rises) -check the Liverpool hepatitis interaction checker.
    • Check hepatitis B status first (reactivation during treatment).
  • After cure -people with cirrhosis still need 6-monthly HCC surveillance; continue harm reduction (needle exchange, opioid substitution) and retest RNA if at ongoing risk (re-infection).
  • No vaccine -prevention is harm reduction, safe medical practice and testing; the NHS aims to eliminate hepatitis C as a public health threat.
Hepatitis E
  • Genotype 3 (the UK and Europe) -from undercooked pork (sausages, pork liver), game and shellfish; often silent, or mild hepatitis in older men.
    • Neurological complications -Guillain–Barré syndrome, neuralgic amyotrophy (severe shoulder pain then weakness).
    • Chronic infection in immunosuppressed people (transplant recipients, chemotherapy, HIV) -progressive liver fibrosis; treat by reducing immunosuppression and with ribavirin.
  • Genotypes 1 and 2 (South Asia, Africa -contaminated water) -outbreaks; severe in pregnancy (acute liver failure, high maternal mortality in the third trimester).
  • Diagnosis -HEV IgM and HEV RNA (PCR -essential in immunosuppressed people, who may not make antibodies).
  • Prevention -cook pork thoroughly; blood donations in the UK are screened for HEV.
  • Test for hepatitis E in unexplained hepatitis, including suspected drug-induced liver injury (it is often missed).
Who to Screen for Blood-borne Viruses
  • Test for HIV, hepatitis B and hepatitis C together in:
    • People who inject or have injected drugs (and their partners).
    • People born or brought up in countries with high prevalence; migrants (NICE PH43).
    • Men who have sex with men; sex workers; people in prison.
    • People with an STI, unexplained abnormal liver tests, or other indicator conditions.
    • Sexual and household contacts of people with hepatitis B; babies of mothers with hepatitis B or C or HIV.
    • Recipients of blood transfusions before 1991 (hepatitis C) and medical care in high-prevalence countries.
  • Routine settings -antenatal screening (HIV, hepatitis B, syphilis), blood and organ donors, dialysis and transplant patients, before chemotherapy, rituximab and biologics (hepatitis B and C, HIV), and opt-out testing in emergency departments in high-prevalence areas.
  • Healthcare workers -hepatitis B vaccination and response testing; workers doing exposure-prone procedures need clearance for HIV, hepatitis B and C (UKHSA).
After an Exposure
VirusRisk after needlestick from a positive source (approximate)Action
HIVAbout 1 in 300 (much lower if the source has an undetectable viral load)PEP within 72 hours (ideally within 1 hour) for 28 days if indicated; HIV test at baseline and 45 days after PEP finishes
Hepatitis BUp to about 1 in 3 if source is HBeAg-positive and recipient is not immuneCheck recipient's vaccination and anti-HBs; booster or accelerated vaccine course ± HBIG (ideally within 48 hours)
Hepatitis CAbout 1 in 30–50No PEP; baseline testing, then HCV RNA at about 6 and 12 weeks; treat early if infected
  • Immediate first aid -encourage bleeding, wash with soap and running water (don't scrub), irrigate eyes and mouth with water; report to occupational health or the emergency department straight away.
  • Source testing -with the source patient's consent (tested by someone other than the exposed worker).
  • Sexual exposures -PEP through sexual health services or the emergency department; also offer STI testing and emergency contraception.
Drug Reference Table
DrugKey points
Bictegravir–emtricitabine–tenofovir alafenamideCommon single-tablet HIV regimen; separate from antacids, iron, calcium; slight creatinine rise.
Dolutegravir (+ two NRTIs, or with lamivudine)Integrase inhibitor; insomnia, weight gain; chelation with antacids and minerals; used in pregnancy.
Tenofovir disoproxilHIV and hepatitis B; kidney tubular damage, bone loss; PrEP with emtricitabine.
AbacavirTest HLA-B*57:01 first -hypersensitivity.
Efavirenz / rilpivirineVivid dreams, low mood / take with food, no PPIs.
Darunavir with ritonavir or cobicistatBoosted PI; strong CYP3A4 inhibition -no simvastatin; fluticasone causes Cushing's.
Cabotegravir + rilpivirine (injection)Long-acting every 2 months for suppressed patients.
Co-trimoxazolePCP treatment (high dose 21 days ± steroids) and prophylaxis (CD4 under 200); high potassium, rash, marrow.
Pyrimethamine + sulfadiazine + folinic acidCerebral toxoplasmosis.
Liposomal amphotericin + flucytosine → fluconazoleCryptococcal meningitis; delay ART 4–6 weeks.
Ganciclovir / valganciclovirCMV retinitis; marrow suppression.
Clarithromycin + ethambutolMAC.
Tenofovir–emtricitabine + raltegravirHIV PEP for 28 days, within 72 hours.
Entecavir / tenofovirChronic hepatitis B -long-term; stopping can cause flares; prophylaxis before rituximab.
Peginterferon alfaHepatitis B (and D) in selected patients; flu-like, depression, cytopenias.
Hepatitis B vaccine + HBIGBabies of infected mothers within 24 hours; post-exposure.
BulevirtideChronic hepatitis D (specialist).
Sofosbuvir–velpatasvir / glecaprevir–pibrentasvirHepatitis C -12 / 8 weeks, over 95% cure; no amiodarone with sofosbuvir; check HBV.
RibavirinChronic hepatitis E in immunosuppression; haemolysis; teratogenic.
Hepatitis A vaccineTravellers, MSM, PWID, chronic liver disease; post-exposure within 14 days.
Spot the Diagnosis
ClueDiagnosis
Fever, rash, mouth ulcers and sore throat 3 weeks after condomless sex; EBV negativePrimary HIV infection
Shingles in two dermatomes in a 30-year-oldHIV indicator condition -offer a test
Dry cough, desaturation on walking, perihilar haziness; CD4 90Pneumocystis pneumonia
Multiple ring-enhancing basal ganglia lesions; CD4 40Cerebral toxoplasmosis
Subacute headache, very high CSF opening pressure; CD4 30Cryptococcal meningitis
Floaters and retinal haemorrhages with white patches; CD4 20CMV retinitis
Purple papules on the palate and legs in a man with HIVKaposi's sarcoma
Fever and enlarging neck nodes 3 weeks after starting ART during TB treatmentTB-IRIS
Rash and fever 1 week after starting abacavirAbacavir hypersensitivity (HLA-B*57:01)
Cushingoid features on ritonavir and a fluticasone inhalerCYP3A4 interaction -iatrogenic Cushing's
Viral load undetectable for over 6 monthsU=U -no sexual transmission
Jaundice 4 weeks after eating shellfish abroad; IgM positiveHepatitis A
HBsAg negative, anti-HBc negative, anti-HBs positiveImmune from vaccination
HBsAg negative, anti-HBc positive, anti-HBs positivePast infection -reactivation risk with rituximab
HBsAg positive for 8 months, HBeAg negative, low DNA, normal ALTHBeAg-negative chronic infection ("inactive carrier") -monitor
Severe hepatitis flare after stopping tenofovirHepatitis B rebound
Rapid cirrhosis in a man with chronic hepatitis B from Eastern EuropeHepatitis D superinfection
HCV antibody positive, RNA negativePast infection -cleared or cured
Vasculitic rash, neuropathy and proteinuria in a former injecting drug userHepatitis C cryoglobulinaemia
Bradycardia after starting hepatitis C treatment on amiodaroneSofosbuvir–amiodarone interaction
Hepatitis with severe shoulder pain then arm weakness after eating sausagesHepatitis E with neuralgic amyotrophy
Persistent hepatitis in a kidney transplant recipient, HEV RNA positiveChronic hepatitis E -reduce immunosuppression, ribavirin
Acute liver failure in a pregnant woman returning from South AsiaHepatitis E (genotype 1)
Exam-style Scenarios

1. A 27-year-old man has had fever, a rash on his trunk, sore throat and mouth ulcers for 5 days. A glandular fever test is negative. He had condomless anal sex with a new male partner 4 weeks ago.
Answer: Possible primary HIV infection.

  • Offer a fourth-generation HIV test and an HIV viral load (antibody may not yet be positive); test for syphilis, hepatitis B and C and other STIs.
  • If positive -urgent referral to the HIV service; start ART promptly; partner notification; advise condoms until undetectable.
  • If negative but suspicion remains -repeat testing; discuss PrEP for the future.

2. A 44-year-old man has had a dry cough and breathlessness for 3 weeks. He desaturates to 86% on walking. Chest X-ray shows bilateral perihilar haziness. A rapid HIV test is positive; CD4 is 60.
Answer: Pneumocystis pneumonia in newly diagnosed advanced HIV.

  • High-dose co-trimoxazole for 21 days (check G6PD if at risk); prednisolone if PaO2 is under 9.3 kPa (start with antibiotics).
  • Confirm with induced sputum or bronchoscopy PCR; screen for other OIs (cryptococcal antigen, TB, CMV), hepatitis B and C, syphilis.
  • Start ART within about 2 weeks (HIV team); then co-trimoxazole prophylaxis until CD4 recovers.

3. A 63-year-old woman is about to start rituximab-based chemotherapy for lymphoma. Hepatitis B tests: HBsAg negative, anti-HBc positive, anti-HBs positive. HBV DNA not detected.
Answer: Past (resolved) hepatitis B infection with high reactivation risk on rituximab.

  • Start antiviral prophylaxis (e.g. entecavir) before chemotherapy and continue for months after rituximab finishes (specialist advice).
  • Monitor HBV DNA and LFTs during treatment.
  • Test HIV and hepatitis C as well before chemotherapy.

4. A 52-year-old man with HIV, well controlled on darunavir with cobicistat plus two NRTIs, is started on simvastatin 40 mg by his GP and uses a fluticasone nasal spray for rhinitis. Two months later he has muscle pain, weight gain and a round face.
Answer: CYP3A4 interactions -statin myopathy and iatrogenic Cushing's syndrome with adrenal suppression.

  • Stop simvastatin (check CK); use a statin with fewer interactions at low dose (e.g. rosuvastatin or atorvastatin with advice).
  • Switch fluticasone to a non-interacting option (e.g. beclometasone); don't stop steroids abruptly if adrenal suppression is suspected -check morning cortisol, steroid cover and endocrine advice.
  • Always check the Liverpool interaction checker before prescribing.

5. A 30-year-old woman who injects drugs is found to be HCV antibody positive and HCV RNA positive. She also has no hepatitis B immunity.
Answer: Chronic hepatitis C -offer treatment now.

  • Assess fibrosis (FibroScan), test HIV and HBV; 8–12 weeks of pangenotypic DAAs (can be delivered in drug services); check interactions.
  • Hepatitis B (and A) vaccination; harm reduction -needle exchange, opioid substitution therapy, naloxone.
  • Check SVR12 for cure; retest HCV RNA regularly if risk continues (no immunity to re-infection).
Key Points
  • Offer HIV tests widely -verbal consent; test anyone with an indicator condition or STI.
  • A fourth-generation test detects most HIV by 4 weeks; a negative test 45 days after exposure excludes it.
  • Glandular fever-like illness with negative EBV -think primary HIV.
  • PCP (CD4 under 200): dry cough, exertional desaturation -high-dose co-trimoxazole plus steroids if hypoxic.
  • CD4 under 100: toxoplasmosis (multiple ring lesions), cryptococcus; under 50: CMV retinitis, MAC.
  • Start ART for everyone as soon as possible; delay in cryptococcal meningitis.
  • Test HLA-B*57:01 before abacavir.
  • Boosted regimens interact with simvastatin, fluticasone and many others -always check.
  • U=U: an undetectable viral load for 6 months means no sexual transmission.
  • PrEP prevents HIV; PEP within 72 hours for 28 days.
  • Hepatitis A and E are faecal–oral; B, C and D are blood-borne.
  • HBsAg = current infection; anti-HBs = immunity; anti-HBc = exposure (never from vaccination).
  • Most newborns infected with hepatitis B become chronic carriers; most adults clear it.
  • Babies of mothers with hepatitis B -vaccine within 24 hours ± HBIG.
  • Test HBsAg and anti-HBc before rituximab, chemotherapy, biologics and HCV treatment.
  • Test all people with hepatitis B for hepatitis D.
  • HCV antibody shows exposure; RNA shows current infection.
  • Hepatitis C is curable in 8–12 weeks; avoid sofosbuvir with amiodarone.
  • Hepatitis E -undercooked pork in the UK; chronic in immunosuppression; severe in pregnancy (genotype 1).
Guidelines and Further Reading
  • BHIVA, BASHH and BIA: UK National Guidelines for HIV Testing
  • NICE NG60: HIV testing -increasing uptake among people who may have undiagnosed HIV
  • BHIVA guidelines: treatment of HIV-1-positive adults with ART; opportunistic infections; HIV in pregnancy and infant feeding
  • BHIVA and BASHH: HIV pre-exposure prophylaxis (PrEP) guidelines; UK guideline for post-exposure prophylaxis (PEP)
  • NICE CG165: Hepatitis B (chronic) -diagnosis and management
  • NICE PH43: Hepatitis B and C testing
  • NICE TAs: direct-acting antivirals for hepatitis C; bulevirtide for hepatitis D
  • EASL Clinical Practice Guidelines on hepatitis B, C and E
  • UKHSA Green Book: Hepatitis A and Hepatitis B chapters
  • University of Liverpool: HIV and hepatitis drug interaction checkers
  • BNF -for current doses
End of chapter 119