HIV infection and AIDS
Exam Tips
- If you see recurrent oral thrush, shingles in a younger adult, weight loss, persistent lymphadenopathy, or TB/STI history, actively offer an HIV test (indicator-condition approach).
- Primary HIV often mimics glandular fever but with high infectivity due to very high viral load.
- Advanced HIV disease is clinically defined by CD4 <200 cells/microlitre or an AIDS-defining condition.
- For prescribing stations: mention baseline tests before ART (viral load, CD4, resistance genotype, renal/liver profile, HBV/HCV, HLA-B*57:01 if abacavir considered).
- State key safety points: abacavir hypersensitivity (HLA-B*57:01), tenofovir renal/bone toxicity, major drug interactions (especially boosted ART and steroid/cation interactions).
- Use the public-health line accurately: sustained undetectable viral load means no sexual transmission (U=U).
Definition
HIV infection is a chronic infection caused by human immunodeficiency virus (a lentivirus retrovirus) that progressively impairs cell-mediated immunity, mainly through loss and dysfunction of CD4 T lymphocytes. Clinically it evolves from possible acute seroconversion illness to a prolonged asymptomatic phase and, without effective treatment, to advanced HIV disease (historically AIDS), defined by severe immunosuppression (CD4 <200 cells/microlitre) or AIDS-defining opportunistic disease/malignancy.
Pathophysiology
HIV enters CD4-expressing cells (especially CD4 T cells, macrophages, dendritic cells) via gp120 binding to CD4 and co-receptors (CCR5 early, sometimes CXCR4 later), then uses reverse transcriptase to generate proviral DNA, integrase to insert into host genome, and protease-mediated maturation to produce infectious virions. Early infection causes very high viraemia and high transmissibility; partial immune control lowers viraemia but persistent replication and chronic immune activation drive gradual CD4 decline, immune exhaustion, and susceptibility to opportunistic infection, malignancy, and non-AIDS comorbidity (cardiovascular, renal, neurocognitive, metabolic). Effective ART suppresses viral replication to undetectable levels, allows immune recovery, and prevents sexual transmission (U=U). See figure of the HIV replication cycle (entry, reverse transcription, integration, budding/maturation) in standard infectious disease textbooks.
Risk Factors
- Condomless vaginal/anal sex, multiple partners, and high-risk sexual practices (including chemsex)
- Men who have sex with men, trans women, and trans men with additional exposure risk
- People who inject drugs and sharing injecting equipment
- Sex workers and people in prisons/closed settings
- People from high HIV prevalence countries (>1% diagnosed seroprevalence), including some Black African communities in UK data
- Current or previous STI (for example syphilis, gonorrhoea, chlamydia)
- Sexual partner living with HIV or from a high-prevalence setting
- Mother living with HIV (vertical risk context)
- Blood products, transplants, or invasive procedures in settings with inadequate screening
- Occupational sharps/mucosal exposure and sexual assault
Clinical Features
Symptoms
- Acute seroconversion (typically 2-4 weeks): fever, sore throat, rash, fatigue, myalgia, headache
- Generalized lymphadenopathy, night sweats, weight loss, diarrhoea
- Mucocutaneous symptoms: oral candidiasis, mouth ulcers, shingles, recurrent HSV
- Asymptomatic phase may be prolonged despite ongoing infectivity
- Later disease: recurrent infections, breathlessness/cough, neurocognitive change, peripheral neuropathic symptoms, mood disturbance
Signs
- Pyrexia and non-specific viral exanthem in primary infection
- Generalized non-tender lymphadenopathy
- Oral thrush, oral hairy leukoplakia, gingival disease
- Dermatological findings (seborrhoeic dermatitis, warts, molluscum contagiosum, psoriasis flares)
- Weight loss/wasting and signs of opportunistic infection in advanced disease
- Features of AIDS-defining illness (for example PCP hypoxia/tachypnoea, Kaposi lesions)
Investigations
Management
Lifestyle Modifications
- Specialist HIV clinic follow-up with rapid linkage to care after diagnosis
- Partner notification, STI screening, and risk-reduction counselling (condoms, safer injecting advice)
- Discuss U=U clearly once sustained undetectable viral load is achieved
- Vaccination review (for example influenza, pneumococcal, hepatitis A/B if indicated)
- Smoking cessation, cardiovascular risk reduction, mental health and substance-use support
- Advice on pregnancy planning, breastfeeding considerations, and prevention of vertical transmission with specialist teams
Pharmacological Treatment
Initial antiretroviral therapy (INSTI-based, typical UK first-line)
- Bictegravir/emtricitabine/tenofovir alafenamide 50 mg/200 mg/25 mg once daily
- Dolutegravir 50 mg once daily plus emtricitabine/tenofovir disoproxil 200 mg/245 mg once daily
- Dolutegravir 50 mg once daily plus abacavir/lamivudine 600 mg/300 mg once daily (only if HLA-B*57:01 negative and suitable)
Start ART promptly after diagnosis. Check interactions before prescribing (notably enzyme inducers, polyvalent cations with integrase inhibitors, and boosted regimens). Avoid abacavir if HLA-B*57:01 positive or prior hypersensitivity; caution abacavir in high cardiovascular risk. Tenofovir disoproxil may worsen renal function/bone mineral density; monitor eGFR and consider alternatives in renal disease.
Opportunistic infection treatment/prophylaxis (selected examples)
- Co-trimoxazole 960 mg once daily for PCP prophylaxis in advanced immunosuppression (local protocol dependent)
- Pneumocystis pneumonia treatment: high-dose co-trimoxazole (trimethoprim component 15-20 mg/kg/day in divided doses) with adjunctive prednisolone when hypoxic
Use according to CD4 count, clinical scenario, and specialist advice. Monitor for sulfonamide reactions, cytopenias, renal effects, and hyperkalaemia.
Prevention pharmacotherapy in at-risk HIV-negative individuals
- PrEP: emtricitabine/tenofovir disoproxil 200 mg/245 mg once daily (or event-based regimen in eligible cisgender MSM as per UK guidance)
- PEPSE: emtricitabine/tenofovir disoproxil 200 mg/245 mg once daily plus raltegravir 1200 mg once daily for 28 days (start as soon as possible, ideally <24 h, no later than 72 h)
Not treatment for established HIV, but essential in UK transmission prevention pathways. Confirm HIV-negative status where required and monitor renal function for tenofovir-containing regimens.
Complications
- Advanced HIV disease with AIDS-defining opportunistic infections (for example Pneumocystis jirovecii pneumonia, tuberculosis, oesophageal candidiasis, cerebral toxoplasmosis)
- AIDS-defining malignancy (for example Kaposi sarcoma, certain non-Hodgkin lymphomas, invasive cervical cancer)
- Chronic HIV and immune-activation morbidity: cardiovascular disease (MI, stroke, heart failure)
- Neurological complications: HIV-associated neurocognitive disorder, peripheral neuropathy, dementia
- Renal disease including HIV-associated nephropathy and ART-related nephrotoxicity
- Metabolic/bone disease: insulin resistance, dyslipidaemia, osteopenia/osteoporosis
- Haematological abnormalities: anaemia, neutropenia, thrombocytopenia
- Psychological morbidity: depression, anxiety, PTSD, insomnia, addiction, self-harm risk
Prognosis
With early diagnosis, immediate and sustained ART, and good adherence, most people in the UK can achieve durable viral suppression, avoid progression to advanced disease, and have near-normal life expectancy. Prognosis worsens with late presentation, treatment interruption, resistance, major co-infection (especially TB/hepatitis), or significant comorbidity; however, sexual transmission risk falls to effectively zero when viral load remains undetectable (U=U).
Sources & References
🏥BMJ Best Practice(1)
💊BNF Drug References(21)
- Abacavir[management.pharmacological]
- Abacavir with lamivudine[management.pharmacological]
- Atazanavir[management.pharmacological]
- Atazanavir with cobicistat[management.pharmacological]
- Darunavir with cobicistat[management.pharmacological]
- Dolutegravir[management.pharmacological]
- Doravirine[management.pharmacological]
- Efavirenz[management.pharmacological]
- Emtricitabine[management.pharmacological]
- Emtricitabine with tenofovir alafenamide[management.pharmacological]
- Enfuvirtide[management.pharmacological]
- Fosamprenavir[management.pharmacological]
- Fostemsavir[management.pharmacological]
- Lamivudine[management.pharmacological]
- Lenacapavir[management.pharmacological]
- Lopinavir with ritonavir[management.pharmacological]
- Maraviroc[management.pharmacological]
- Nevirapine[management.pharmacological]
- Ritonavir[management.pharmacological]
- Zidovudine[management.pharmacological]
- Zidovudine with lamivudine[management.pharmacological]
✅NICE Guidelines(1)
- HIV infection and AIDS[overview]