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Stem
A 34-year-old man who has sex with men presents to the emergency department with a 5-day history of fever (39 deg C), sore throat, generalised maculopapular rash that involves his palms and soles, and painless oral and penile ulcers. He reports unprotected receptive anal intercourse with two new partners 3 weeks ago. On examination he has cervical and inguinal lymphadenopathy, blood pressure 118/74, pulse 96, oxygen saturation 98% on air. Bloods: white cell count 2.9 (mild lymphopenia), platelets 110, ALT 92, normal bilirubin. A rapid HIV antibody test is negative; Monospot negative; VDRL non-reactive.
Questions
a) What is the most likely diagnosis and what single investigation confirms it? (2 marks)
The most likely diagnosis is acute (primary) HIV infection (seroconversion illness). The presentation — fever, rash involving palms and soles, mucocutaneous ulcers, lymphadenopathy, mild cytopenia and transaminitis 2 to 4 weeks after a high-risk sexual exposure — is the classic mononucleosis-like illness of primary HIV. The rapid antibody test is negative because the patient is seroconverting. The diagnostic test is HIV-1 RNA nucleic acid amplification (viral load by RT-PCR) — classically very high (often over 1 million copies/mL). A p24 antigen is also typically positive; a 4th-generation Ag/Ab combo assay is likely reactive (for p24) but the HIV-1/2 differentiation may be negative or indeterminate.
b) Outline the natural history of untreated HIV infection. (3 marks)
- Primary (acute) infection at 2 to 4 weeks: mononucleosis-like illness with high viraemia and a sharp CD4 dip; the virus establishes the latent reservoir in long-lived resting memory CD4+ T cells.
- Chronic (clinical latency) lasting 8 to 10 years untreated (range 1 to 15+): patient is well but CD4 falls steadily (50 to 100 cells/uL per year) and HIV RNA remains detectable with massive viral turnover (about 10 billion virions per day). Minor opportunistic conditions begin as CD4 drops below 500 (oral candidiasis, oral hairy leukoplakia, seborrhoeic dermatitis, recurrent Herpes zoster, ITP, cervical dysplasia).
- AIDS at CD4 under 200: opportunistic infections and malignancies by CD4 ladder — under 200 PJP, oral hairy leukoplakia, Kaposi sarcoma, recurrent bacterial pneumonia, extrapulmonary TB; under 100 cerebral toxoplasmosis, cryptococcal meningitis, cryptosporidiosis; under 50 CMV retinitis, disseminated MAC, primary CNS lymphoma, PML.
c) Outline the immediate management. (3 marks)
- Confirm the diagnosis with HIV-1 RNA PCR and a 4th-generation Ag/Ab combo; baseline CD4 count, viral load, genotypic resistance testing, hepatitis B/C serology, syphilis and other STI screening, TB symptom screen, HLA-B*5701 if abacavir considered, G6PD if dapsone considered, FBC/U&E/LFT/glucose/lipids, pregnancy test (irrelevant here), cervical/anal cytology.
- Start combination antiretroviral therapy (cART) immediately — the START trial established ART for all adults regardless of CD4. Preferred first-line: 2 NRTIs + 1 INSTI — e.g. tenofovir (TDF) + emtricitabine (FTC) + dolutegravir (DTG) or bictegravir/TAF/FTC. Early therapy limits the reservoir size and reduces onward transmission (high viral load in primary infection).
- Partner notification and prevention: notify and offer testing to recent sexual contacts; offer PEP within 72 hours to exposed partners; counsel on U=U once viral load is suppressed; screen for and treat any co-existing STI; consider PrEP for ongoing risk.
- Psychosocial support — counselling, mental health, linkage to HIV care, adherence support.
d) What are the key complications of untreated advanced HIV? (2 marks)
- Opportunistic infections: PJP, pulmonary and extrapulmonary TB, cerebral toxoplasmosis, cryptococcal meningitis, CMV retinitis/colitis, disseminated MAC, cryptosporidiosis, oesophageal candidiasis, recurrent bacterial pneumonia, HSV/VZV.
- AIDS-defining malignancies: Kaposi sarcoma (HHV-8), non-Hodgkin lymphoma (including primary CNS lymphoma, EBV-driven), invasive cervical carcinoma (HPV).
- Other: HIV-associated neurocognitive disorder (HAND), HIV wasting syndrome, HIV-associated nephropathy (HIVAN), progressive multifocal leukoencephalopathy (PML, JC virus), immune cytopenias (ITP), increased cardiovascular disease, osteoporosis.
- Immune reconstitution inflammatory syndrome (IRIS) may complicate the first weeks of ART (paradoxical worsening of a known OI).