Overview
HIV Seroconversion & Acute HIV
1. Clinical Overview
Summary
Acute HIV infection (seroconversion illness) occurs 2-6 weeks after exposure and presents as a non-specific viral syndrome resembling glandular fever — fever, rash, pharyngitis, and lymphadenopathy. It is frequently missed but represents the period of highest infectivity. Diagnosis requires 4th generation HIV Ag/Ab testing or HIV RNA PCR. Early diagnosis enables immediate ART initiation, reduces the viral reservoir, and prevents onward transmission.
Key Facts
- Timing: 2-6 weeks post-exposure (median 2-4 weeks)
- Presentation: Fever (80%), pharyngitis (50-70%), rash (50-70%), lymphadenopathy (40-70%)
- Diagnosis: 4th generation HIV Ag/Ab (p24 + antibodies) or HIV RNA PCR
- Highly infectious: Extremely high viral load during acute phase
- Treatment: Start ART as soon as possible — reduces reservoir and transmission
- Frequently missed: Often attributed to "viral illness" or glandular fever
Clinical Pearls
Mononucleosis-like illness with NEGATIVE Monospot + risk factors = think acute HIV
> 4th generation tests detect p24 antigen, allowing diagnosis from ~2 weeks post-exposure
Acute HIV is the most infectious stage — partner notification is critical
Why This Matters Clinically
Recognising acute HIV has major public health implications. Patients with acute HIV have viral loads that can exceed 10 million copies/ml, making them highly infectious. Early diagnosis and ART initiation dramatically reduce onward transmission. Every clinician should consider HIV in patients with unexplained viral syndromes and risk factors.
2. Epidemiology
Visual assets to be added:
- Acute HIV timeline (exposure → seroconversion → chronic infection)
- Typical rash photograph
- Viral load and antibody graph during acute infection
- HIV testing algorithm flowchart
Epidemiology
Incidence & Prevalence
- New HIV diagnoses (UK): ~3,000-4,000 per year
- Acute HIV as presenting illness: 40-90% develop symptomatic seroconversion
- Missed diagnoses: Up to 75% of acute HIV cases not diagnosed during acute phase
- Global prevalence: 38 million people living with HIV worldwide
Demographics
- Age: Peak in 25-34 year age group
- Sex: In UK, majority in men who have sex with men (MSM)
- Heterosexual transmission: Increasing proportion, especially in migrants from high-prevalence countries
- IVDU: Less common in UK but remains a risk globally
Risk Factors for Acquisition
| High Risk | Moderate Risk |
|---|---|
| Unprotected anal intercourse | Unprotected vaginal intercourse |
| Multiple sexual partners | Sexual partner with HIV |
| Sharing injecting equipment | STI (especially genital ulcer diseases) |
| Occupational exposure (needlestick) | Sex work |
| Chemsex | Blood transfusion in endemic area |
3. Pathophysiology
HIV Virology
- Virus: HIV-1 (most common globally), HIV-2 (West Africa primarily)
- Target: CD4+ T lymphocytes, macrophages, dendritic cells
- Receptor: CD4 + co-receptor (CCR5 or CXCR4)
- Effect: Progressive immune destruction → AIDS
Acute Infection Timeline
| Phase | Week | Events |
|---|---|---|
| Eclipse phase | 0-1 | Virus replicating locally; not yet detectable |
| Viraemia | 1-3 | Massive viral replication; HIV RNA detectable |
| Peak viraemia | 3-4 | Viral load peaks (often > million copies/ml); p24 detectable |
| Seroconversion | 4-8 | Antibodies develop; symptoms coincide with immune response |
| Set point | 6-12 | Viral load stabilises; chronic infection begins |
Immunopathogenesis of Acute Symptoms
- Symptoms result from immune response to high viral load, not direct viral cytopathy
- Cytokine release → flu-like symptoms
- CD4 depletion begins in acute phase (especially gut-associated lymphoid tissue)
- Early treatment may preserve immune function
4. Clinical Presentation
Typical Presentation (Acute Retroviral Syndrome)
Onset 2-4 weeks post-exposure, lasting 2-4 weeks:
Atypical/Severe Presentations
Red Flags — When to Suspect Acute HIV
| Clinical Feature | Suggestive Finding |
|---|---|
| Illness type | Glandular fever-like with NEGATIVE Monospot |
| Rash | Non-itchy, maculopapular, trunk/face |
| Oral ulcers | Multiple, shallow, painful |
| Risk history | Recent unprotected sex, chemsex, new partner, condom failure |
| STI history | Recent STI diagnosis |
Fever (80%) — often high (>38.5°C)
Common presentation.
Fatigue/malaise (70%)
Common presentation.
Maculopapular rash (50-70%) — trunk/face, non-pruritic
Common presentation.
Pharyngitis (50-70%)
Common presentation.
Lymphadenopathy (40-70%) — generalised
Common presentation.
Headache (40%)
Common presentation.
Oral ulcers (30-40%) — often multiple, painful
Common presentation.
Myalgia/arthralgia (30-60%)
Common presentation.
5. Clinical Examination
Focused History
- Sexual history: Partners, condom use, type of sexual contact
- Timeline: When was the potential exposure?
- Other exposures: IVDU, occupational, blood products
- STI history: Previous diagnoses
- Symptom timeline: When did symptoms start relative to exposure?
Physical Examination
| System | Findings |
|---|---|
| General | Fever, unwell appearance |
| Skin | Maculopapular rash (trunk, face, palms/soles) |
| Oropharynx | Pharyngitis, tonsillar enlargement, oral ulcers |
| Lymph nodes | Generalised lymphadenopathy (cervical, axillary, inguinal) |
| Abdomen | Hepatosplenomegaly (20%) |
| Neurological | Rarely: meningism, cranial nerve palsies |
| Genital | Check for STI co-infection |
6. Investigations
HIV Testing
| Test | Detects | Window Period |
|---|---|---|
| 4th gen Ag/Ab | p24 antigen + HIV-1/2 antibodies | ~4 weeks (p24 from 2-3 weeks) |
| HIV RNA PCR | Viral nucleic acid | ~10 days (earliest detection) |
| 3rd gen Ab only | HIV antibodies | ~6-8 weeks |
Testing Strategy in Suspected Acute HIV
- 4th generation Ag/Ab test (standard)
- If negative but high suspicion: HIV RNA PCR
- If negative, repeat at 6 weeks and 3 months
Additional Investigations at Diagnosis
- CD4 count: Baseline immune status
- HIV viral load: Usually extremely high in acute infection
- HIV resistance genotype: Before starting ART
- STI screen: Full screen (syphilis, gonorrhoea, chlamydia, Hep B, Hep C)
- Baseline bloods: FBC, U&E, LFTs, lipids, HbA1c
Classification & Staging
HIV Disease Staging (WHO)
| Stage | Features |
|---|---|
| Primary HIV infection | Acute seroconversion illness |
| Clinical Stage 1 | Asymptomatic, persistent generalised lymphadenopathy |
| Clinical Stage 2 | Mild symptoms (weight loss <10%, minor mucocutaneous) |
| Clinical Stage 3 | Moderate immunodeficiency (weight loss >0%, chronic diarrhoea, oral candidiasis) |
| Clinical Stage 4 (AIDS) | Severe immunodeficiency (opportunistic infections, Kaposi's, wasting) |
CD4 Count Categories
| CD4 Count | Interpretation |
|---|---|
| >00 cells/μL | Normal range |
| 350-500 | Mild immunosuppression |
| 200-350 | Moderate immunosuppression |
| <200 | Severe immunosuppression (AIDS-defining) |
7. Management
Immediate Management
- Confirm diagnosis: 4th gen test + HIV RNA if needed
- Start ART as soon as possible: Same-day or within 1-2 weeks
- Baseline investigations: CD4, VL, resistance, STI screen
- Partner notification: Sexual health advisor involvement
Antiretroviral Therapy
- Start immediately — don't wait for confirmatory tests if diagnosis is clear
- First-line regimens: Usually 2 NRTIs + integrase inhibitor
- Example: Bictegravir/emtricitabine/tenofovir alafenamide (single tablet regimen)
Partner Notification
- Essential — acute HIV is highly transmissible
- Sexual health advisers facilitate contact tracing
- Partners may need PEP if exposure <72 hours ago
Post-Exposure Prophylaxis (PEP)
- For sexual or occupational exposure BEFORE seroconversion
- Start within 72 hours of exposure
- 28-day course of ART
Follow-Up
- Regular CD4 and viral load monitoring
- Adherence support
- Mental health screening
- Long-term cardiovascular risk management
8. Complications
Acute Phase Complications
- Neurological: Aseptic meningitis, encephalopathy, GBS-like syndrome
- Opportunistic infections: Rare in acute HIV but possible if severely immunocompromised
- Transmission to partners: Highest risk during acute phase
Long-Term Complications (Without Treatment)
- AIDS-defining illnesses: PCP, Kaposi's sarcoma, CMV, cryptococcal meningitis
- Malignancies: NHL, cervical cancer, Kaposi's
- Cardiovascular disease: Accelerated atherosclerosis
- Neurocognitive impairment
- Chronic inflammation and immune activation
With Early ART
- Excellent prognosis: Near-normal life expectancy
- Undetectable = Untransmittable (U=U): No sexual transmission risk when virally suppressed
9. Prognosis & Outcomes
Natural History (Without Treatment)
- Median time to AIDS: ~10 years (range 2-20+ years)
- Median survival after AIDS: ~2 years without treatment
- Long-term non-progressors: ~5% maintain high CD4 without ART
With Modern ART
- Viral suppression: >95% achieve undetectable viral load
- Life expectancy: Near-normal if diagnosed early and adherent to ART
- Quality of life: Excellent with good adherence
Prognostic Factors
| Favourable | Unfavourable |
|---|---|
| Early diagnosis and ART | Late presentation (CD4 <200) |
| High CD4 at diagnosis | High viral load set-point |
| Good adherence | Drug resistance |
| Younger age | Older age |
| Absence of co-morbidities | Hepatitis B/C co-infection |
10. Evidence & Guidelines
Key Guidelines
- BHIVA Guidelines for HIV Treatment (2022)
- BHIVA/BASHH UK Guidelines for HIV Testing (2020)
- WHO Consolidated Guidelines on HIV (2021)
Key Evidence
START Trial (2015)
- Early ART (CD4 >500) vs deferred (CD4 <350)
- 57% reduction in serious AIDS/death with early treatment
- Now standard to treat all HIV-positive individuals regardless of CD4
PARTNER/PARTNER2 Trials (2019)
- Zero transmissions from virally suppressed individuals
- Established U=U (Undetectable = Untransmittable)
HPTN 052 (2011)
- 96% reduction in transmission with early ART
- Foundation for "treatment as prevention"
11. Patient/Layperson Explanation
What is Acute HIV?
Acute HIV infection is the first stage of HIV infection. It can cause flu-like symptoms 2-4 weeks after exposure. Many people don't realise they have it because the symptoms are similar to other viral illnesses.
What are the Symptoms?
- Fever, sore throat, swollen glands
- Rash (often on trunk and face)
- Mouth ulcers
- Muscle aches, headache
- Fatigue
Why is Testing Important?
- During acute HIV, you are VERY infectious to others
- Early treatment protects your health and prevents transmission
- Modern HIV treatment is highly effective — people with HIV live normal, healthy lives
What Happens if I Test Positive?
- You will be linked to specialist HIV care
- Treatment is started promptly (usually same week)
- With treatment, HIV is a manageable chronic condition
- Undetectable = Untransmittable: When treated, you cannot pass HIV to partners
Resources
12. References
Primary Guidelines
- Waters L, et al. BHIVA Guidelines for the Treatment of HIV-1-positive Adults with Antiretroviral Therapy 2022. HIV Med. 2022. bhiva.org
- Gazzard BG, et al. BHIVA/BASHH UK Guidelines for HIV Testing 2020. HIV Med. 2020. PMID: 32515525
- WHO. Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring. 2021. who.int
Key Trials
- INSIGHT START Study Group. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015;373(9):795-807. PMID: 26192873
- Rodger AJ, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet. 2019;393(10189):2428-2438. PMID: 31056293