Key Facts

HIV infection remains a major public health concern in the UK. Early diagnosis and treatment with ART is key to achieving viral suppression, preventing transmission, and enabling near-normal life expectancy. The UK has adopted the UNAIDS 95-95-95 targets.

Epidemiology

• ~106,000 people living with HIV in the UK (PHE/UKHSA data)
• New diagnoses: ~3,000–4,000 per year (declining)
• Late diagnosis (CD4 <350 at diagnosis): ~42% — associated with 10-fold increased mortality in first year
• Men who have sex with men (MSM): largest affected group; heterosexual transmission second
• Mother-to-child transmission rate <0.5% with effective interventions
• Life expectancy with early ART: near-normal

Aetiology

• HIV-1: predominant worldwide (subtypes A–K); HIV-2: West Africa, less pathogenic
• Transmission: sexual (vaginal, anal), parenteral (needlestick, IVDU), vertical (pregnancy, delivery, breastfeeding)
• NOT transmitted by: casual contact, kissing, sharing utensils, mosquitoes

Pathophysiology

• HIV is an RNA retrovirus (Retroviridae, genus Lentivirus)
• Binds CD4 receptor + co-receptor (CCR5 or CXCR4) on T-helper cells, macrophages, dendritic cells
• Reverse transcriptase converts RNA → DNA → integration into host genome (provirus)
• Viral replication destroys CD4+ T cells → progressive immunodeficiency
• Acute seroconversion: viraemia peak → immune response → set point viral load
• Without treatment: CD4 declines ~50–80 cells/µL per year → AIDS in ~8–10 years
• Chronic immune activation drives comorbidities (CVD, neurocognitive decline, malignancy)

Primary HIV Infection (Seroconversion — 2–6 weeks post-exposure)

• Occurs in ~60–80% of newly infected; often misdiagnosed as glandular fever
• Fever, sore throat, lymphadenopathy, maculopapular rash, myalgia
• Oral ulceration, diarrhoea, headache
• Rarely: aseptic meningitis, Guillain-Barré syndrome

Asymptomatic Phase (Clinical Latency)

• May last years without treatment
• Persistent generalised lymphadenopathy
• Gradual CD4 decline

Symptomatic HIV (CD4 200–500)

• Oral candidiasis, oral hairy leukoplakia
• Herpes zoster (multidermatomal)
• Seborrhoeic dermatitis, recurrent bacterial infections
• Constitutional symptoms: weight loss, night sweats, diarrhoea

AIDS (CD4 <200 or AIDS-defining illness)

• PCP (Pneumocystis jirovecii pneumonia): dry cough, dyspnoea, bilateral perihilar infiltrates
• Cerebral toxoplasmosis: ring-enhancing lesions, seizures, focal neurology
• Cryptococcal meningitis: headache, fever, raised ICP
• CMV: retinitis (pizza-pie fundus), colitis, oesophagitis
• Kaposi sarcoma: violaceous skin lesions, HHV-8 associated
• TB: pulmonary or extrapulmonary (atypical presentations at low CD4)

Red Flags

• Fever with new respiratory symptoms in known/suspected HIV
• New neurological symptoms (headache, confusion, focal signs)
• New visual symptoms (CMV retinitis emergency)
• Severe weight loss (>10% body weight)
• CD4 <100 with any new symptom

Bedside

• HIV test: 4th-generation combined antigen/antibody test (detects p24 antigen + HIV-1/2 antibodies)
• Window period: 45 days for 4th-gen test
• Point-of-care rapid test: fingerprick — result in 20 minutes

Bloods

• Confirmatory test: HIV-1/2 differentiation assay
• HIV RNA viral load: quantify viraemia (baseline and monitoring)
• CD4 count: staging and prophylaxis decisions
• HIV resistance genotyping: before starting ART
• FBC, U&Es, LFTs, lipids, glucose, HbA1c: baseline metabolic assessment
• Hepatitis B/C serology: high co-infection rates
• Syphilis serology: RPR/VDRL + TPHA
• Toxoplasma IgG: baseline (for future prophylaxis decisions)
• CMV IgG: baseline
• HLA-B*5701: before abacavir (hypersensitivity risk)

Imaging

• CXR: baseline and if respiratory symptoms
• CT/MRI brain: if neurological symptoms

Special Tests

• Cervical smear: annual (increased HPV/cervical cancer risk)
• DEXA scan: if risk factors for osteoporosis
• Cardiovascular risk assessment: QRISK3 (HIV increases CV risk)
• Neurocognitive screening: for HIV-associated neurocognitive disorder

Non-pharmacological

• Partner notification: supported by sexual health services
• Barrier contraception advice
• Smoking cessation, lifestyle modification: CV risk reduction
• Psychological support: high rates of depression, stigma
• Adherence support: essential for viral suppression

Pharmacological

Antiretroviral therapy (ART) — start in ALL patients (NICE NG211, BHIVA):

• Preferred first-line: tenofovir alafenamide/emtricitabine + dolutegravir (TAF/FTC + DTG)
• Alternative: tenofovir disoproxil/emtricitabine + dolutegravir (TDF/FTC + DTG)
• Single-tablet regimens available: Triumeq (ABC/3TC/DTG), Biktarvy (TAF/FTC/BIC)
• Viral load target: <50 copies/mL by 6 months

Opportunistic infection prophylaxis:

• CD4 <200: co-trimoxazole 960mg OD (PCP prophylaxis) — continue until CD4 >200 for 3 months
• CD4 <100 + Toxoplasma IgG+: co-trimoxazole also covers toxoplasmosis
• CD4 <50 + CMV IgG+: regular fundoscopy; consider valganciclovir if retinitis
• Latent TB: treat if IGRA positive (isoniazid 300mg + pyridoxine 10mg for 6 months, or rifampicin + isoniazid for 3 months)

Landmark trials:

• START trial: immediate ART (any CD4) superior to deferred (CD4 <350)
• PARTNER/PARTNER2: U=U — zero linked transmissions with VL <200
• HPTN 052: early ART reduced transmission by 96%

Surgical/Interventional

• Not routinely required
• Surgical management of complications (lymphoma, Kaposi sarcoma)

Referral Criteria

• All newly diagnosed: specialist HIV clinic (GUM/infectious diseases)
• Pregnancy: joint HIV/obstetric care
• Complex comorbidities: multidisciplinary team
• Drug resistance or treatment failure: specialist MDT review

• With early ART: near-normal life expectancy (within 5–10 years of HIV-negative population)
• Late diagnosis (CD4 <200): 10-fold increased mortality in first year vs early diagnosis
• Virological suppression (VL <50): >95% achieve with modern ART
• AIDS-related mortality in UK: declining rapidly with widespread ART
• Major causes of death in treated HIV: non-AIDS cancers, cardiovascular disease, liver disease (often hepatitis co-infection)
• CD4 recovery: most patients achieve CD4 >500 within 2–3 years of ART if started early
• U=U: zero sexual transmission risk with sustained viral suppression

WHO Clinical Staging

CD4-Related Infections

ART Drug Classes