Preparatory Mindset
HIV/AIDS is the defining chronic infection of our era — 38 million people living with HIV globally (UNAIDS 2021), 1 (CM exam tested).15 million in China (NCAIDS 2021), with 97.9% of new Chinese cases transmitted sexually. The exam mindset: any young/middle-aged adult with persistent generalised lymphadenopathy + recurrent opportunistic infection + chronic diarrhoea + weight loss → think HIV → HIV test (4th-generation Ag/Ab) is the universal screen. The clinical landscape is divided into acute HIV (seroconversion), chronic asymptomatic HIV, and AIDS (CD4 <200, opportunistic infections + malignancies). Treatment is lifelong combination antiretroviral therapy (cART / HAART) — modern regimens suppress viral load to undetectable, restore CD4, and prevent transmission (U=U: undetectable = untransmittable). Prevention rests on testing + PrEP/PEP + condom + harm reduction.
Core Concepts
1. Definition
HIV = Human Immunodeficiency Virus, a retrovirus that infects and depletes CD4⁺ T lymphocytes, leading to progressive immune deficiency. AIDS = Acquired Immunodeficiency Syndrome, the late clinical stage of HIV infection defined by CD4 <200 cells/μL or the presence of AIDS-defining illnesses.
2. Aetiology
| Feature | Detail |
|---|---|
| Family | Retroviridae, subfamily Lentivirus |
| Genome | Single-stranded RNA, ~9.8 kb, enveloped, diploid |
| Types | HIV-1 (main, global); HIV-2 (West Africa, less virulent, less efficiently transmitted) |
| Major genes | gag (nucleocapsid), pol (reverse transcriptase, integrase, protease), env (gp120, gp41) |
| Accessory genes | nef, tat, rev — regulate replication |
| Diversity | High mutation rate (reverse transcriptase error-prone); many subtypes — HIV-1 group M (A, B, C, D, F, G, H, J, CRF); HIV-2 (A–G) |
| Stability | Inactivated 100 °C × 20 min; survives 15 days at room temperature in fluid; 3 days on contaminated items; inactivated by 75% ethanol, bleach, 4% formalin, 0.5% cresol, 0.3% H₂O₂ |
3. Replication cycle (key targets)
- Attachment — gp120 binds CD4 + CCR5 (or CXCR4) co-receptor
- Fusion — gp41 mediates membrane fusion
- Uncoating
- Reverse transcription — RNA → DNA (target of NRTIs, NNRTIs)
- Integration — DNA → provirus (target of integrase inhibitors, INSTIs)
- Transcription / translation — using host machinery
- Assembly + budding — protease cleaves polyprotein (target of protease inhibitors, PIs)
4. Cells infected
- Major targets in vivo: CD4⁺ T lymphocytes, monocytes/macrophages
- Minor targets: Langerhans cells, CD34⁺ precursors, triple-negative thymocytes, dendritic cells
- In vitro / low level: FDC, CD8, B cells, NK, megakaryocytes, astrocytes, microglia, mucosal cells, cervix, trophoblast, testis, prostate
5. Epidemiology
- Global: 38.4 million PLHIV (2021); 1.5 million new cases/year; 650,000 AIDS-related deaths/year. Sub-Saharan Africa carries the largest burden.
- China: 1.148 million PLHIV, 385,000 cumulative deaths (up to 2021); 129,377 newly reported in 2021. Sexual transmission = 97.9% (heterosexual 71.4%, MSM 26.5%). New diagnoses in elderly (≥60) rising sharply (94.3% heterosexual).
- Three links of the chain: Source = HIV-infected person. Route = blood, sexual, perinatal (MTCT). Susceptible = non-infected, especially with risk exposure (MSM, IVDU, commercial sex, blood exposure).
6. Natural history (untreated)
| Stage | CD4 | Duration | Clinical |
|---|---|---|---|
| Acute HIV (seroconversion) | Normal / ↓ | 2–4 weeks post-exposure | Mononucleosis-like: fever, rash, lymphadenopathy, pharyngitis, myalgia, mucocutaneous ulcers; window period for Ab tests |
| Chronic asymptomatic HIV | Gradual ↓ | 2–10+ years | Often silent; persistent generalised lymphadenopathy (PGL) |
| AIDS | <200 cells/μL | Variable | Opportunistic infections + malignancies + wasting |
7. Clinical staging — WHO & CDC
| WHO stage | Features |
|---|---|
| 1 | Asymptomatic, PGL |
| 2 | Weight loss <10%, minor mucocutaneous, recurrent URI |
| 3 | Weight loss >10%, chronic diarrhoea >1 mo, persistent fever, oral thrush, severe bacterial infections, pulmonary TB |
| 4 (AIDS) | AIDS-defining illnesses (see below) |
AIDS-defining illnesses (selected):
- Infections: *Pneumocystis jirovecii* pneumonia (PJP/PCP), disseminated *Mycobacterium avium* complex (MAC), disseminated histoplasmosis, chronic cryptosporidiosis, CMV disease (retinitis, oesophagitis), TB, recurrent bacterial pneumonia, candidiasis (oesophageal/tracheal/bronchial), cryptococcal meningitis, progressive multifocal leukoencephalopathy (PML, JC virus), recurrent HSV, toxoplasmosis (CNS)
- Malignancies: Kaposi sarcoma (HHV-8), CNS lymphoma, cervical cancer (HPV), Burkitt lymphoma
- Wasting syndrome, HIV encephalopathy
8. Diagnosis
| Test | Detail |
|---|---|
| HIV screening (4th-generation Ag/Ab) | Detects HIV-1/2 antibody + p24 antigen; window 2–4 weeks post-exposure; if reactive → confirmatory test |
| Confirmatory | HIV-1/HIV-2 antibody differentiation immunoassay; if discordant → HIV-1 RNA (NAAT/PCR) |
| CD4 count | Stage marker; threshold for OI prophylaxis (<200 → PJP prophylaxis, <150 → MAC prophylaxis historically, less common with early cART) |
| HIV viral load (RNA) | Treatment response target <50 copies/mL (undetectable) |
| Resistance testing | Genotype at baseline + before regimen change |
| STI screening | Syphilis, HBV, HCV, gonorrhoea, chlamydia |
| Baseline labs | CBC, LFT, renal function, fasting lipids, glucose, urinalysis, pregnancy test, HLA-B*5701 (if abacavir planned), tropism (if CCR5 antagonist planned) |
> Window period: If acute HIV suspected (recent exposure, mononucleosis-like) and 4th-gen test negative, repeat at 2–4 weeks and/or do HIV RNA PCR (detects ~7–10 days post-exposure).
9. Treatment — combination antiretroviral therapy (cART / HAART)
Goal: suppress HIV RNA to undetectable (<50 copies/mL) within 3–6 months; restore CD4; prevent AIDS, OIs, death, and transmission (U=U).
Standard initial regimens (WHO/Chinese guidelines, 2024+):
| Backbone (2 NRTIs) | Third drug |
|---|---|
| Tenofovir (TDF or TAF) + Emtricitabine (FTC) (or Lamivudine, 3TC) | Dolutegravir (DTG) — INSTI, first-line, once daily |
| Tenofovir + Lamivudine | Bictegravir (BIC) — INSTI, single-tablet |
| Abacavir + Lamivudine (if HLA-B*5701 negative) | Dolutegravir |
Single-tablet regimens (STR): TDF/FTC + DTG (often branded); TAF/FTC/BIC; many options.
Older regimens (still used in select cases): efavirenz (NNRTI), protease inhibitor + ritonavir/cobicistat boosting.
When to start: immediately upon diagnosis, regardless of CD4 ("treat all"). Acute HIV → start within 2 weeks if possible.
Monitoring:
- Viral load at 4–8 weeks, then 3–6 months; target undetectable by 3–6 months.
- CD4 every 3–6 months until stable >350.
- LFT, renal function, lipids, glucose periodically (drug toxicities).
Drug toxicity highlights:
| Drug | Key toxicity |
|---|---|
| Tenofovir (TDF) | Renal dysfunction, ↓ bone density (TAF less so) |
| Abacavir | Hypersensitivity (HLA-B*5701 positive) — screen before use |
| Dolutegravir / INSTIs | Well tolerated; mild weight gain; rare neuropsychiatric (DTG) |
| Efavirenz | CNS vivid dreams, rash, hepatotoxicity; avoid in pregnancy 1st trimester (neural tube defect risk) |
| Protease inhibitors | GI intolerance, hyperlipidaemia, insulin resistance, lipodystrophy |
10. Opportunistic infection prophylaxis
| CD4 threshold | Prophylaxis |
|---|---|
| <200 | TMP-SMX for PJP (PCP) — also covers toxoplasmosis |
| <150 + positive Toxoplasma IgG | TMP-SMX (higher dose) for toxoplasmosis |
| <50 | Add azithromycin for MAC (less commonly used with universal early cART) |
| Latent TB | Isoniazid + pyridoxine × 6–9 months |
| HBV | Treat as part of HIV regimen (TDF/FTC active against HBV) |
| Cryptococcus (CD4 <100 + high CrAg) | Fluconazole (screen CrAg if CD4 <100 in some settings) |
11. Post-exposure prophylaxis (PEP)
Occupational (needlestick) or non-occupational (sexual assault, condom break):
- Start within 72 h, ideally as soon as possible
- 3-drug regimen × 28 days (TDF/FTC + DTG or raltegravir)
- HIV testing at baseline, 6 weeks, 12 weeks, 6 months
12. Pre-exposure prophylaxis (PrEP)
- Daily oral TDF/FTC for high-risk individuals (MSM, IVDU, serodiscordant couples); event-driven ("2-1-1") for MSM (2 pills 2–24 h before, then 1 at 24 h, 1 at 48 h).
- Injectable cabotegravir (long-acting) approved in some settings.
13. Mother-to-child transmission (MTCT)
- All pregnant women should be tested for HIV.
- If HIV+: immediate cART (DTG-based), scheduled C-section if viral load >1000 at delivery, avoid breastfeeding (in resource-rich settings; in resource-poor, exclusive breastfeeding + maternal cART is acceptable), neonatal prophylaxis (zidovudine or nevirapine × 4–6 weeks).
- Risk of MTCT <1% with effective cART.
14. Prevention and notification
- Condom use, harm reduction (needle exchange, opioid substitution therapy for IVDU), universal precautions in healthcare.
- Voluntary medical male circumcision reduces heterosexual female-to-male transmission by ~60%.
- Notification: Class B notifiable disease (24 h).
High-Yield Points
| Topic | Must-remember |
|---|---|
| Pathogen | HIV-1 (Retroviridae, Lentivirus) — main global type |
| Target | CD4⁺ T cells + macrophages (CD4 + CCR5/CXCR4) |
| Diagnosis | 4th-gen Ag/Ab screen → confirmatory differentiation assay → HIV RNA if discordant |
| Window | 4th-gen ~2–4 weeks; HIV RNA ~7–10 days |
| cART | TDF/FTC + DTG (first-line); start immediately at diagnosis ("treat all") |
| Goal | Undetectable = Untransmittable (U=U) |
| AIDS threshold | CD4 <200 cells/μL or AIDS-defining illness |
| PJP prophylaxis | TMP-SMX at CD4 <200 |
| MAC prophylaxis | Azithromycin at CD4 <50 (less used with early cART) |
| PEP | Within 72 h, 3-drug × 28 days |
| PrEP | Daily TDF/FTC for high-risk |
| MTCT | Effective cART → <1% transmission; C-section if VL >1000 |
| Abacavir | Screen HLA-B*5701 before use |
| Efavirenz | Avoid in 1st-trimester pregnancy |
Topic Summary
HIV is a retrovirus that depletes CD4⁺ T cells, leading over years to AIDS (CD4 <200 + OIs/malignancies). Transmission is blood, sexual, perinatal — in China, 97.9% sexual (heterosexual + MSM). Diagnosis: 4th-gen Ag/Ab screen → confirmatory → HIV RNA if needed; start cART immediately regardless of CD4. First-line regimen: TDF/FTC + dolutegravir; goal = undetectable viral load (U=U). Prophylaxis: TMP-SMX at CD4 <200 for PJP; PEP within 72 h for exposure; PrEP for high-risk. Class B notifiable disease.
LMCHK OSCE Practice — Newly Diagnosed HIV — Initial Counselling
Station setup: 32-year-old male, just confirmed HIV-positive (4th-gen + confirmatory). Asymptomatic, CD4 380 cells/μL, HIV RNA 50,000 copies/mL, normal LFT/renal, negative for hepatitis B/C/syphilis. He is anxious and asks what to do next.
Candidate tasks (8 min):
- Explain the diagnosis in plain language — chronic manageable condition, not the death sentence it once was, with effective treatment.
- Discuss immediate next steps: baseline labs (renal, LFT, lipids), start cART today (TDF/FTC + DTG), review vaccinations (hepatitis B, pneumococcal, influenza), screen sexual partners.
- Counsel on U=U: with adherence, viral suppression means zero risk of sexual transmission; condom use still recommended for STI prevention.
- Discuss PrEP for HIV-negative partner(s).
- Provide psychological support referral and discuss confidentiality / notification obligations.
Key marking cues:
- Treats with empathy and non-judgment.
- Explains treat-all principle and immediate cART (TDF/FTC + DTG first-line).
- Mentions U=U as a key motivator for adherence.
- Screens for TB, HBV, HCV, syphilis, STI at baseline.
- Discusses partner notification (with patient consent and confidentiality).
- Schedules viral load at 4–8 weeks, then 3–6 months.
Companion station — Needlestick exposure:
A 28-year-old nurse has a needlestick from an HIV+ source patient (HIV RNA 200,000 copies/mL, not on cART).
- Start PEP within 72 h: TDF/FTC + DTG × 28 days.
- HIV testing at baseline, 6 weeks, 12 weeks, 6 months.
- Counsel about side effects, adherence, follow-up.
- Report occupational exposure per institutional protocol.