Human Immunodeficiency Virus and co infections

Below is a **complete, exhaustive, exam-ready, clinician-level HIV master note** covering **everything that exists about HIV on the planet**—virology, epidemiology, pathophysiology, natural history, clinical features, diagnosis, staging, treatment (ALL classes with mechanism & dosing), prophylaxis, opportunistic infections, prevention, pregnancy guidance, resistance, monitoring, and global facts. I will follow your required **medical-reference pattern**: **Definition → Virology → Epidemiology → Transmission → Pathogenesis → Natural History → Clinical Features → WHO/CDC Staging → Investigations/Diagnosis → Differential Diagnoses → Treatment (full ART table with drugs, MOA, dosing, PK, side effects, contraindications, interactions, monitoring, counselling) → Opportunistic infections summary → PEP → PrEP → Pregnancy → Vaccines (none) → Resistance → Prognosis → Public health.** --- # **HIV (Human Immunodeficiency Virus) — Complete Master Detailed Note** --- # **1. DEFINITION** **HIV** is a retrovirus (lentivirus subgroup) causing **progressive destruction of CD4+ T lymphocytes**, leading to **immunodeficiency** and predisposing to **opportunistic infections, malignancies, and AIDS-defining conditions**. --- # **2. VIROLOGY (EXISTING KNOWLEDGE ON THE PLANET)** * Family: **Retroviridae** * Genus: **Lentivirus** * Two major types: * **HIV-1** (global pandemic, 95% cases) * **HIV-2** (West Africa, slower disease progression) * HIV-1 Groups: * **Group M** (major – subtypes A, B, C, D, F, G, H, J, K) * **Group O, N, P** (rare) * **Subtype C** = most prevalent globally (India, Africa) * Envelope: **gp120, gp41** → responsible for cell entry * Core proteins: **p24 antigen** ### **Genome** * Single-stranded, positive-sense **RNA** * Key enzymes: * **Reverse transcriptase** * **Integrase** * **Protease** ### **Cell Entry Mechanism** 1. gp120 binds **CD4 receptor** 2. Co-receptor binding: * **CCR5** (early infection, mucosal transmission) * **CXCR4** (late stages) 3. gp41 mediates fusion. 4. Reverse transcription → integration → replication. --- # **3. EPIDEMIOLOGY** * **~39 million people living with HIV worldwide (2025).** * New infections/year globally ~1.5 million. * Africa accounts for **67%** of global HIV burden. * Highest prevalence: **Eswatini, Lesotho, Botswana, South Africa** * India: about **2.3 million people** with HIV. * Major affected populations: * MSM * Sex workers * People who inject drugs * Transgender population * Infants of HIV-positive mothers * Serodiscordant couples --- # **4. TRANSMISSION** **Most to least efficient:** 1. **Blood transfusion** (95% risk) 2. **Mother-to-child** 3. **Needle-sharing** 4. **Unprotected anal intercourse** 5. **Unprotected vaginal intercourse** 6. **Oral sex** (low risk) 7. **Kissing, touching, insects = NO RISK** ### **Mother-to-child** * In utero → 5–10% * During labor → 15–20% * Breastfeeding → 10–20% * Total without therapy → **30–45%** * With ART → **<1%** --- # **5. PATHOGENESIS** * Primary infection → high viral load * Massive CD4 depletion in GALT (gut) * Chronic infection → immune activation → CD4 decline * AIDS when: * **CD4 < 200** OR * AIDS-defining illness --- # **6. NATURAL HISTORY (If Untreated)** 1. **Acute retroviral syndrome** 2. **Clinical latency (asymptomatic)** 3. **Persistent generalized lymphadenopathy** 4. **Symptomatic infection (CD4 < 500)** 5. **AIDS (CD4 < 200 or AIDS-defining illness)** --- # **7. CLINICAL FEATURES** ### **Acute HIV (2–6 weeks)** * Fever * Lymphadenopathy * Rash (maculopapular) * Pharyngitis * Diarrhea * Headache * Aseptic meningitis ### **Chronic HIV** * Persistent lymphadenopathy * Chronic diarrhea * Weight loss * Herpes zoster * Oral candidiasis * Recurrent respiratory infections ### **AIDS-defining illnesses** * Pneumocystis jirovecii pneumonia * CNS toxoplasmosis * CMV retinitis * Cryptococcal meningitis * Kaposi sarcoma * Non-Hodgkin lymphoma * Esophageal candidiasis * Mycobacterium avium complex (MAC) --- # **8. STAGING** ## **CDC CD4-based staging** * Stage 1: **CD4 ≥ 500** * Stage 2: **CD4 200–499** * Stage 3: **CD4 < 200 or AIDS** ## **WHO Staging (1–4)** * Stage 1: Asymptomatic * Stage 2: Mild disease (recurrent URIs, zoster) * Stage 3: Severe weight loss, TB, chronic diarrhea * Stage 4: AIDS conditions --- # **9. INVESTIGATIONS & DIAGNOSIS** ### **Screening** * HIV 1&2 **4th generation test (antigen + antibody)** Detects: * p24 antigen (early, ~10–15 days) * HIV antibodies (~3–12 weeks) ### **Confirmatory** * Western blot (older) * HIV-1/HIV-2 differentiation assay ### **Viral Load** * HIV RNA PCR Used for: * Monitoring ART * Diagnosis in neonates (<18 months) ### **CD4 Count** * Immune status monitoring. ### **Other baseline tests** * HBsAg, HCV * CBC, LFT, RFT * Pregnancy test * Resistance testing (genotype) * TB screening * Lipid & glucose profile --- # **10. DIFFERENTIAL DIAGNOSIS** * Acute mononucleosis * CMV infection * Secondary syphilis * Dengue (acute HIV-like presentation) * COVID acute viral syndrome * Lymphoma (advanced HIV weight loss) * TB --- # **11. TREATMENT OF HIV** **ART is lifelong. Start treatment in EVERY HIV-positive patient—regardless of CD4.** # **FIRST-LINE ART REGIMENS (GLOBAL STANDARD 2025)** ## **A. INSTI-based regimen (preferred worldwide)** ### **1. Tenofovir + Lamivudine + Dolutegravir (TLD)** * TDF 300 mg + 3TC 300 mg + DTG 50 mg once daily ### **2. Tenofovir alafenamide (TAF) + FTC + Bictegravir (Biktarvy)** * Once daily ### **3. Dolutegravir + Lamivudine dual therapy** * For stable patients. --- # **ART DRUGS — COMPLETE DETAILED TABLE (GLOBAL KNOWLEDGE)** ### *(Indication, MOA, Dosing, PK, Side-effects, Contra, Interactions, Monitoring, Counselling)* --- ## **A. NRTIs (Nucleoside RT inhibitors)** **TDF, TAF, Lamivudine (3TC), Emtricitabine (FTC), Abacavir (ABC)** ### Mechanism * Competitive inhibition of reverse transcriptase → chain termination. ### Key Drugs ### 1. **Tenofovir disoproxil fumarate (TDF)** * **Dose:** 300 mg daily * **PK:** renal clearance * **Side effects:** renal toxicity, Fanconi syndrome, ↓ bone density * **Monitor:** creatinine, phosphate * **Contra:** severe renal failure * **Counselling:** hydration, bone health ### 2. **Tenofovir alafenamide (TAF)** * Less renal & bone toxicity * Preferred in pregnancy. ### 3. **Lamivudine (3TC) / Emtricitabine (FTC)** * Excellent tolerability * HBV-active drugs ### 4. **Abacavir (ABC)** * **HLA-B*5701 testing required** * Risk: hypersensitivity, MI risk debated. --- ## **B. NNRTIs (Efavirenz, Nevirapine, Rilpivirine, Doravirine)** ### MOA: * Bind reverse transcriptase non-competitively. ### Efavirenz (EFV) * Side effects: vivid dreams, anxiety, suicidality * Teratogenic concerns early pregnancy (old data) * Interactions via CYP450 --- ## **C. INSTIs (Dolutegravir, Bictegravir, Raltegravir)** ### MOA: * Inhibit integrase enzyme → prevents viral DNA integration ### **Dolutegravir (DTG)** * **Most preferred drug globally** * High resistance barrier * Side effects: insomnia, weight gain * Avoid with dofetilide * Safe in pregnancy (now confirmed) ### Bictegravir * Similar to DTG, used in Biktarvy * Few interactions --- ## **D. Protease inhibitors (PIs)** ### MOA: * Block viral protease → non-infectious virions Drugs: Atazanavir, Darunavir, Lopinavir Need boosting with ritonavir/cobicistat. Side effects: * Metabolic syndrome * Hyperlipidemia * Indirect hyperbilirubinemia (atazanavir) --- ## **E. Entry inhibitors** * Maraviroc (CCR5 antagonist) * Enfuvirtide (fusion inhibitor) Reserved for resistant HIV. --- # **12. MONITORING** * Viral load: baseline, 3 months, 6 months → annually * CD4: baseline → annually * Creatinine (TDF) * LFTs * Lipid profile --- # **13. OPPORTUNISTIC INFECTION (OI) PROPHYLAXIS** ### **CD4 < 200 → PCP prophylaxis** * TMP-SMX daily ### **CD4 < 100 → Toxoplasmosis prophylaxis** * TMP-SMX ### **CD4 < 50 → MAC prophylaxis** * Azithromycin 1200 mg weekly --- # **14. POST-EXPOSURE PROPHYLAXIS (PEP)** * Start **within 72 hours** * Duration: **28 days** * Preferred: * **TDF + 3TC + Dolutegravir** --- # **15. PRE-EXPOSURE PROPHYLAXIS (PrEP)** * **TDF + FTC** once daily * Reduces HIV risk >99% --- # **16. HIV IN PREGNANCY** * Continue ART * DTG-based regimens are safe * C-section only if: * Viral load >1000 * Avoid breastfeeding if safe alternatives available * Give infant **Nevirapine prophylaxis** * MTCT reduced to **<1%** with ART. --- # **17. HIV & VACCINES** * No vaccine yet (as of 2025) * All trials failed: RV144 (Thailand), Mosaico, Imbokodo. --- # **18. HIV DRUG RESISTANCE** * Mutations: M184V (3TC), K65R (TDF), K103N (EFV) * DTG has highest resistance barrier. --- # **19. PROGNOSIS** * With ART: **Near-normal life expectancy** * Without ART: Median survival ~9–11 years after infection. --- # **20. GLOBAL PUBLIC HEALTH IMPACT** * End HIV/AIDS target: **2030 (UNAIDS)** * Biggest barriers: * Late diagnosis * Stigma * Poor ART adherence * Access inequality --- If you want, I can also generate: ✅ **35 case scenarios (real-life + management)** ✅ **Hard MCQs (HTML + CSS + JS in one file)** ✅ **Differential diagnosis tables** ✅ **Opportunistic infections full reference** ✅ **Pregnancy flowchart** Just tell me what you need next. I’ll structure this as: 1. Core concept of HIV + opportunistic infections (OIs) 2. Key OIs by CD4 level 3. General diagnostic & management principles (incl. IRIS) 4. Prophylaxis (primary + secondary) – with CD4 cut-offs 5. Focus drug notes (TMP-SMX, dapsone, atovaquone, azithromycin, isoniazid, fluconazole) 6. **25 case scenarios** with management + prophylaxis angle > **Exam note**: Doses, thresholds and regimens are based on current HIV/OI guidelines (NIH/CDC/WHO/UpToDate) as of late-2025; always adapt to your local protocol. ([ClinicalInfo][1]) --- ## 1. Concept: HIV, coinfections and opportunistic infections **Definition** * **Opportunistic infection (OI)**: infection that occurs with increased frequency/severity when immunity is impaired, especially **CD4 T-cell depletion** in HIV. * **Coinfection**: presence of HIV plus **another pathogen** (e.g. TB, HBV, HCV, malaria, STIs) which may or may not be opportunistic but interacts with HIV (worse progression, higher viral load, drug interactions). ([CDC][2]) **Pathophysiology** * Progressive HIV replication → CD4 decline → failure of **cell-mediated immunity** → reactivation of latent infections (TB, toxoplasma, CMV) and new infections (PCP, cryptococcus, MAC). * OIs themselves increase HIV viral load transiently and accelerate disease. ([CDC][2]) * Starting ART may trigger **IRIS (Immune Reconstitution Inflammatory Syndrome)**: recovering immune system mounts exaggerated response to existing antigen load → paradoxical clinical deterioration (e.g. worse TB lymphadenitis, increased ICP in cryptococcal meningitis). ([NACO][3]) --- ## 2. Important OIs & typical CD4 thresholds Approximate **CD4 levels** at which OIs are common: * **Any CD4**: TB, bacterial pneumonia/sepsis, oral candidiasis, herpes zoster. * **<200 cells/µL**: * **Pneumocystis jirovecii pneumonia (PCP/PJP)** ([ASM Journals][4]) * Recurrent bacterial pneumonia. * **<100 cells/µL**: * **Toxoplasma gondii encephalitis** (if IgG⁺). ([UpToDate][5]) * **Cryptococcal meningitis**, disseminated cryptococcosis. ([ASM Journals][6]) * **<50 cells/µL**: * **Mycobacterium avium complex (MAC)** (disseminated). ([bhiva.org][7]) * CMV retinitis, CMV colitis. ([nhstaysideadtc.scot.nhs.uk][8]) You’ll often see questions coupling: * CD4 180 → PCP * CD4 60 + ring-enhancing lesions → toxoplasma * CD4 30 + meningitis with ↑OP → cryptococcus * CD4 20 + fever, hepatosplenomegaly, ALP↑ → MAC --- ## 3. Diagnostic & management principles ### A. General diagnostic work-up in advanced HIV * Full history: ART adherence, **CD4 trend**, VL, prior OIs, prophylaxis. * Physical: skin lesions (Kaposi, molluscum), mucosal candidiasis, focal neurologic signs, neck stiffness. * Baseline labs: CBC, LFT, RFT, electrolytes, LDH, blood cultures. * HIV-specific: current VL, CD4 count. * Imaging: * CXR/HRCT for pneumonia (PCP: bilateral interstitial infiltrates). * CT/MRI brain for focal lesions (toxoplasma, lymphoma). * OI-specific tests: * **PCP**: induced sputum / BAL with silver stain, PCR. * **Toxoplasma**: MRI ring-enhancing lesions + IgG serology; definitive = brain biopsy. ([Medscape Education][9]) * **Cryptococcal**: serum/CSF cryptococcal antigen (CrAg), India ink, fungal culture. ([ASM Journals][6]) * **MAC**: blood cultures, bone marrow culture. ([National Health Mission][10]) * **TB**: GeneXpert/NAAT, cultures; extrapulmonary sampling. ### B. General treatment principles 1. **Stabilise the patient first** * ABC, oxygen, treat sepsis, manage raised ICP (cryptococcus), control seizures, correct electrolytes. 2. **Specific OI treatment** * PCP: high-dose TMP-SMX ± steroids. ([ClinicalInfo][11]) * Toxoplasma encephalitis: pyrimethamine + sulfadiazine + leucovorin (or TMP-SMX high-dose). ([ClinicalInfo][12]) * Cryptococcal meningitis: amphotericin B + flucytosine induction → fluconazole consolidation + maintenance. ([New England Journal of Medicine][13]) * MAC: macrolide (clarithro/azithro) + ethambutol ± rifabutin. ([National Health Mission][10]) * TB: standard HRZE with attention to **rifampicin–ART interactions**. 3. **When to start ART in acute OI** (adult, typical exam stance) * **PCP, toxoplasma, MAC, most bacterial OIs**: start ART within ~2 weeks once patient stabilizes. * **TB**: within 2 weeks if CD4 <50; by 8 weeks if ≥50 (and no CNS TB). * **Cryptococcal meningitis & TB meningitis**: delay ART ~4–6 weeks due to severe CNS-IRIS risk. ([The Lancet][14]) 4. **Secondary prophylaxis / chronic maintenance** Continue specific suppressive therapy until immune reconstitution (details in prophylaxis section). 5. **Manage drug interactions & toxicities** * Check for **overlap**: marrow suppression (zidovudine + TMP-SMX + ganciclovir), nephrotoxicity (tenofovir + amphotericin), hepatotoxicity (TB drugs + azoles + ART), QT prolongation (macrolides, fluoroquinolones, some ARVs). --- ## 4. Prophylaxis strategy: what, when to start, when to stop ### A. Primary prophylaxis (prevent first episode) **PCP** * **Indication** (Adults): * CD4 **<200 cells/µL** OR * CD4% <14% OR * Oropharyngeal candidiasis or unexplained fever >2 weeks, even if CD4 >200. ([ASM Journals][4]) * **Preferred regimen**: * TMP-SMX 1 DS (160/800 mg) **once daily**. * **Alternatives** (if sulfa intolerance): * Dapsone 100 mg daily ± pyrimethamine + leucovorin, or * Atovaquone 1500 mg PO daily with food. ([NACO][3]) * **Stop** when CD4 ≥200 for ≥3 months on ART (and VL suppressed). Restart if CD4 <100 or 100–200 with viremia. ([bccfe.ca][15]) **Toxoplasma gondii encephalitis (TE)** * **Indications**: * Toxoplasma IgG positive + CD4 **<100 cells/µL**. ([ClinicalInfo][12]) * **Preferred prophylaxis**: * TMP-SMX 1 DS once daily (same as PCP prophylaxis). * **Alternatives**: * Dapsone 50 mg daily + pyrimethamine 50 mg weekly + leucovorin, etc. ([NACO][3]) * **Stop** when CD4 >200 for ≥3 months on ART (or 100–200 with sustained VL suppression). ([bccfe.ca][16]) **MAC (disseminated)** * **Modern guidelines**: If ART is started promptly and VL suppressed, **routine primary prophylaxis is generally NOT recommended**. ([hiv.uw.edu][17]) * If used (e.g. cannot start ART, CD4 <50): * Azithromycin 1200 mg weekly PO (or 600 mg twice weekly). ([bhiva.org][7]) **Cryptococcus** * Many programs: **CrAg screening** for CD4 <100. * If **asymptomatic CrAg-positive**: high-dose fluconazole 800 mg/day for 2 weeks, then 400 mg/day 8–10 weeks, then 200 mg/day until immune recovery (pre-emptive treatment = a form of prophylaxis). ([ASM Journals][6]) **TB (latent)** * All PLHIV should be screened with symptom screen + TST/IGRA where available. * **Isoniazid preventive therapy (IPT)**: INH 300 mg daily + pyridoxine 25–50 mg daily for 6–9 months in latent TB or high-burden settings, irrespective of CD4. ### B. Secondary prophylaxis (after an OI) * **PCP** – lower-dose TMP-SMX (e.g. 1 SS daily) until CD4 ≥200 for ≥3 months on ART. ([bccfe.ca][15]) * **Toxoplasma encephalitis** – reduced-dose pyrimethamine + sulfadiazine + leucovorin OR TMP-SMX DS daily until CD4 ≥200 for ≥6 months on ART. ([bccfe.ca][16]) * **Cryptococcal meningitis** – fluconazole 200 mg daily for at least 1 year and until CD4 ≥100–200 with suppressed VL. ([bccfe.ca][18]) * **MAC** – clarithro/azithro + ethambutol until ≥12 months of therapy AND CD4 ≥100 for ≥6 months. ([National Health Mission][10]) --- ## 5. High-yield drug mini-monographs (for OI prophylaxis) ### 5.1 Trimethoprim–Sulfamethoxazole (TMP-SMX, co-trimoxazole) * **Indications in HIV** * Primary & secondary **PCP prophylaxis**. * Toxoplasma prophylaxis in IgG⁺ patients. * Treatment of PCP, toxoplasma (high doses). * **Mechanism**: sequential blockade of folate synthesis (sulfamethoxazole: dihydropteroate synthase; trimethoprim: DHF reductase) → inhibits DNA synthesis. * **Usual prophylactic dosing (adults)** * 1 **DS** (160/800 mg) once daily; or 1 SS daily, or 1 DS three times/week if toxicity. ([AAHIVM][19]) * **Paediatric**: 150 mg/m² trimethoprim component once daily (approx 5 mg/kg TMP). * **PK**: good oral absorption, renal elimination; T½ ~10 h. * **Common AEs**: rash, nausea, mild hyperkalaemia, creatinine rise, photosensitivity. * **Serious AEs**: Stevens–Johnson, TEN, severe neutropenia, thrombocytopenia, hepatitis, aseptic meningitis. * **Contraindications**: severe sulfa allergy, major prior SJS/TEN, severe hepatic failure, marked renal failure without dose adjustment, G6PD deficiency (caution). * **Important interactions**: ↑ toxicity with other antifolates (methotrexate), additive marrow suppression with zidovudine, ganciclovir, interferon; ↑ INR with warfarin. * **Monitoring**: CBC, creatinine, K⁺, LFTs; watch for rash. * **Counselling**: take with water, report rash or mucosal lesions immediately; avoid self-stopping – contact provider to discuss desensitization/alternatives. ### 5.2 Dapsone * **Indications**: alternative PCP/toxoplasma prophylaxis in sulfa-intolerant patients. ([NACO][3]) * **Mechanism**: sulfone that inhibits folate synthesis similar to sulfonamides. * **Dose**: 100 mg PO once daily (or 50 mg daily when combined with pyrimethamine weekly). * **PK**: hepatic metabolism, long T½ (~20–30 h). * **AEs**: haemolysis (esp. G6PD deficiency), methaemoglobinaemia, rash, agranulocytosis, peripheral neuropathy. * **Contraindications**: severe G6PD deficiency, previous severe reaction. * **Monitoring**: baseline G6PD, Hb, retic count/met-Hb if symptomatic. * **Counselling**: report dark urine, SOB, cyanosis; don’t use OTC oxidant drugs without advice. ### 5.3 Atovaquone * **Indication**: PCP prophylaxis/alternative treatment when TMP-SMX not tolerated. ([bccfe.ca][15]) * **Mechanism**: inhibits mitochondrial electron transport in protozoa/fungi. * **Dose**: 1500 mg PO once daily **with fatty meal**. * **AEs**: GI upset, rash, headache; generally well tolerated. * **Interactions**: rifampicin & tetracyclines ↓ atovaquone levels; monitor if combined with ART with GI effects. * **Counselling**: must be taken with high-fat food to work; if severe diarrhoea, efficacy reduced. ### 5.4 Azithromycin (for MAC prophylaxis/treatment) * **Indications**: * Primary prophylaxis against disseminated MAC when CD4 <50 and ART cannot be started. * Part of MAC treatment (with ethambutol ± rifabutin). ([bhiva.org][7]) * **Mechanism**: macrolide – 50S ribosomal subunit inhibition. * **Dose (prophylaxis)**: 1200 mg once weekly OR 600 mg twice weekly PO. * **AEs**: GI upset, QT prolongation, mild LFT derangement. * **Interactions**: fewer CYP interactions than clarithromycin but still caution with QT-prolonging ARVs; avoid with strong QT-prolongers. * **Monitoring**: ECG in high-risk; LFTs if prolonged. ### 5.5 Isoniazid (INH) * **Indications**: latent TB treatment / preventive therapy in PLHIV. * **Mechanism**: inhibits mycolic acid synthesis in mycobacteria. * **Dose**: 300 mg PO once daily + pyridoxine 25–50 mg daily for 6–9 months. * **AEs**: hepatotoxicity, peripheral neuropathy, rash, lupus-like syndrome. * **Contraindications**: acute hepatitis, severe chronic liver disease (relative). * **Monitoring**: LFTs baseline & if symptomatic. * **Counselling**: avoid alcohol; report jaundice, neuropathic symptoms early. ### 5.6 Fluconazole * **Indications**: * Pre-emptive therapy in asymptomatic CrAg-positive patients. * Consolidation and maintenance in cryptococcal meningitis. ([ASM Journals][6]) * **Mechanism**: triazole – inhibits fungal 14-α-demethylase → ergosterol synthesis ↓. * **Doses**: * Pre-emptive: 800 mg/day 2 weeks → 400 mg/day 8–10 weeks → 200 mg/day until CD4 recovery. ([NCBI][20]) * Secondary prophylaxis: 200 mg/day long term. * **AEs**: GI upset, rash, alopecia (long-term), hepatotoxicity, QT prolongation. * **Interactions**: CYP2C9/3A4 inhibitor – ↑ levels of warfarin, some ARVs (esp. nevirapine, some protease inhibitors), some antiepileptics. * **Monitoring**: LFTs, ECG if other QT drugs. --- ## 6. 25 case scenarios – coinfections, OIs, management & prophylaxis Each case: **summary → diagnosis → immediate management → prophylaxis plan.** --- ### Case 1 – First presentation with PCP 32-year-old man, newly diagnosed HIV, CD4 120, subacute non-productive cough, progressive dyspnoea, fever, desaturation on exertion; CXR: bilateral perihilar interstitial infiltrates; ABG: A-a gradient high. * **Likely diagnosis**: PCP. * **Management**: hospitalize; high-dose IV/PO TMP-SMX (15–20 mg/kg/day TMP in 3–4 doses) + steroids if PaO₂ <70; start ART after ~2 weeks once stable. * **Prophylaxis**: after treatment, move to TMP-SMX 1 DS daily as secondary prophylaxis until CD4 ≥200 for ≥3 months. --- ### Case 2 – Oral candidiasis as a red flag 28-year-old woman with long-standing HIV, not on ART for 1 year, presents with painful white plaques in mouth, odynophagia. CD4 170. * **Diagnosis**: oropharyngeal/esophageal candidiasis. * **Management**: fluconazole 200 mg loading then 100–200 mg daily 7–14 days (longer if esophageal); start/optimize ART. * **Prophylaxis**: regardless of CD4 (170 <200 and thrush present) → start PCP prophylaxis with TMP-SMX DS daily. --- ### Case 3 – Toxoplasma encephalitis 40-year-old man with HIV, irregular ART, CD4 60, headache, seizures, right hemiparesis. MRI brain: multiple ring-enhancing lesions in basal ganglia; Toxo IgG positive. * **Diagnosis**: Toxoplasma encephalitis. * **Management**: pyrimethamine + sulfadiazine + leucovorin for at least 6 weeks, then secondary prophylaxis; consider high-dose TMP-SMX if first-line unavailable. Delay ART 1–2 weeks. * **Prophylaxis**: after acute Rx → reduced-dose pyrimethamine-sulfadiazine or TMP-SMX DS OD until CD4 >200 for ≥6 months. --- ### Case 4 – Toxoplasma prophylaxis missed Same patient as Case 3 – review history shows toxo IgG⁺ 1 year earlier, CD4 then 80, but no prophylaxis. * **Teaching point**: should have been on **primary prophylaxis** (TMP-SMX DS daily) when IgG⁺ + CD4 <100 to prevent TE. --- ### Case 5 – Cryptococcal meningitis 35-year-old man, CD4 40, presents with subacute headache, fever, blurring of vision; neck stiffness mild; LP: ↑ opening pressure, low glucose, high protein, lymphocytes; CSF India ink +, CrAg strongly positive. * **Diagnosis**: cryptococcal meningitis. * **Management**: * Induction: amphotericin B + flucytosine 2 weeks; manage raised ICP with repeated LPs. * Consolidation: fluconazole 400–800 mg/day 8 weeks. * Maintenance: fluconazole 200 mg/day ≥1 year. ART start delayed ~4–6 weeks. * **Prophylaxis**: maintenance fluconazole (secondary), can stop when CD4 ≥100–200 with sustained viral suppression. --- ### Case 6 – Asymptomatic CrAg-positive screen HIV patient, CD4 45, no symptoms; CrAg screening positive in serum; LP normal. * **Diagnosis**: asymptomatic cryptococcal antigenaemia. * **Management**: oral fluconazole 800 mg/day for 2 weeks → 400 mg/day for 8–10 weeks → 200 mg/day until immune reconstitution; start ART after ~2 weeks if well. * **Prophylaxis**: this regimen is effectively **pre-emptive primary prophylaxis** to prevent meningitis. --- ### Case 7 – Disseminated TB co-infection 29-year-old man, HIV+, newly diagnosed, CD4 110, with fever, weight loss, cough, hepatosplenomegaly, matted cervical nodes; CXR: miliary mottling; Xpert positive for MTB. * **Diagnosis**: disseminated TB in HIV. * **Management**: start HRZE with careful drug–drug interaction planning; start ART within 2 weeks (CD4 <50–100 rule, but many exams accept 2 weeks for severe TB). * **Prophylaxis**: * Household contacts → INH preventive therapy. * After completion of TB therapy, consider INH prophylaxis depending on local guideline & risk. --- ### Case 8 – TB meningitis with HIV 36-year-old HIV+ man CD4 70, chronic headache, fever, cranial nerve palsies; CSF lymphocytic, ADA↑, Xpert positive. * **Diagnosis**: tuberculous meningitis. * **Management**: HRZE with steroids; **delay ART ~4–8 weeks** to reduce CNS IRIS; manage raised ICP. * **Prophylaxis**: as above, no specific secondary prophylaxis, but close follow-up; consider isoniazid preventive therapy after completed regimen in high-risk areas. --- ### Case 9 – MAC in advanced HIV 45-year-old male, CD4 20, not on ART, presents with prolonged fever, weight loss, diarrhoea, abdominal pain, hepatosplenomegaly, high ALP; blood cultures: MAC. * **Diagnosis**: disseminated MAC. * **Management**: azithromycin + ethambutol ± rifabutin for ≥12 months; start ART after 2 weeks. * **Prophylaxis**: secondary prophylaxis continues until CD4 ≥100 for ≥6 months; **primary prophylaxis** with azithro would be considered if he was not starting ART and CD4 <50. --- ### Case 10 – Missed MAC prophylaxis Same patient had CD4 30 six months ago and was not started on ART or MAC prophylaxis. * **Teaching point**: in someone who **cannot** start ART with CD4 <50, MAC prophylaxis with weekly azithromycin (or daily clarithromycin) is indicated. --- ### Case 11 – Recurrent bacterial pneumonias 33-year-old woman, HIV+, CD4 190, two lobar pneumonias in last year, smoker. * **Diagnosis**: recurrent bacterial pneumonia; consider humoral deficiency, smoking, bronchiectasis. * **Management**: treat current episode with appropriate IV antibiotics; smoking cessation; vaccinate with PCV/PPV, influenza. * **Prophylaxis**: ensure PCP prophylaxis (CD4<200), optimize ART, vaccinations (PCV13/PPV23, Hib, flu). --- ### Case 12 – CMV retinitis 37-year-old man, CD4 25, blurred vision, floaters; fundoscopy: “pizza pie” haemorrhagic lesions. * **Diagnosis**: CMV retinitis. * **Management**: systemic valganciclovir ± intravitreal ganciclovir; urgent ophthalmology; start ART within 2 weeks. * **Prophylaxis**: secondary prophylaxis with valganciclovir until CD4 >100–150 for ≥3–6 months. --- ### Case 13 – Kaposi sarcoma with pulmonary OIs 30-year-old man, MSM, HIV+, purple papules on skin, CD4 90, cough, dyspnoea; CXR diffuse infiltrates; bronchoscopy: PCP. * **Diagnosis**: Kaposi sarcoma (cutaneous ± pulmonary) + PCP. * **Management**: treat PCP with TMP-SMX + steroids; start ART; chemo for extensive KS. * **Prophylaxis**: TMP-SMX secondary prophylaxis; routine MAC/TE prophylaxis as per CD4. --- ### Case 14 – HBV coinfection 42-year-old man, HIV-HBV coinfected, high HBV DNA, CD4 350, needs ART. * **Management**: start ART containing **tenofovir (TDF/TAF) + lamivudine/emtricitabine** (dual-active for HBV); avoid stopping these abruptly to prevent HBV flare. * **Prophylaxis note**: HBV treatment here acts as **long-term prophylaxis** against HBV reactivation. --- ### Case 15 – HCV coinfection and OI risk 45-year-old woman, HIV-HCV coinfection, on ART with CD4 260, persistent elevated LFTs, planning HCV DAA therapy. * **Management**: choose DAA regimen compatible with ART; counsel about alcohol cessation; monitor drug interactions. * **Prophylaxis**: OI prophylaxis not indicated (CD4>200, no OI); but vaccinate for HAV/HBV if not immune to prevent severe acute hepatitis. --- ### Case 16 – IRIS with TB lymphadenitis Patient with HIV-TB coinfection started ART 1 week after TB therapy (CD4 30). Six weeks later, lymph nodes enlarge, fever worsens, cultures still negative, adherence good. * **Diagnosis**: paradoxical TB-IRIS. * **Management**: continue TB Rx and ART; give NSAIDs or short course steroids in severe cases; exclude true failure or new OI. * **Prophylaxis**: no change in TMP-SMX or other OI prophylaxis; emphasize adherence. --- ### Case 17 – IRIS in cryptococcal disease HIV patient with cryptococcal meningitis started ART 1 week after amphotericin; 2 weeks later, severe headache, raised ICP. * **Diagnosis**: cryptococcal IRIS; ART started too early. * **Management**: manage raised ICP, consider corticosteroids; **do not stop antifungals**, may need to pause ART temporarily in severe CNS IRIS (per specialist decision). * **Prophylaxis**: same secondary fluconazole; future learning: delay ART 4–6 weeks in cryptococcal meningitis. --- ### Case 18 – Pregnancy with advanced HIV & OIs 27-year-old pregnant woman (24 weeks), newly diagnosed HIV, CD4 130, oral candidiasis and chronic cough; CXR: PCP pattern. * **Management**: TMP-SMX is still first-line for PCP in pregnancy (benefit outweighs risk), plus steroids if indicated; start pregnancy-safe ART (e.g. TDF/3TC/DTG as per current guidelines) after PCP stabilises. * **Prophylaxis**: TMP-SMX prophylaxis will continue (also reduces malaria, bacterial infections in pregnancy in endemic areas); monitor folate and haemoglobin. --- ### Case 19 – Paediatric HIV with PCP 5-year-old child, vertically infected HIV, CD4% 11%, severe tachypnoea, hypoxia, bilateral interstitial changes. * **Diagnosis**: PCP pneumonia in child. * **Management**: IV TMP-SMX 15–20 mg/kg/day TMP component in divided doses + steroids; start/optimize paediatric ART. * **Prophylaxis**: after recovery, TMP-SMX 5 mg/kg TMP once daily as secondary prophylaxis until CD4% >15–20% and stable. --- ### Case 20 – Severe sulfa allergy 30-year-old HIV+ man, CD4 70, had life-threatening SJS with TMP-SMX previously; now needs PCP/TE prophylaxis. * **Management**: **avoid all sulfa drugs.** Use atovaquone 1500 mg OD with food for PCP; for toxoplasma prophylaxis, dapsone-pyrimethamine-leucovorin is generally contraindicated (sulfa); consider atovaquone ± specialist alternatives. * **Prophylaxis**: atovaquone until CD4 >200 for ≥3 months; robust ART. --- ### Case 21 – Malaria coinfection with HIV HIV-positive man in malaria-endemic region, CD4 220, presents with fever, anaemia, positive P. falciparum smear. * **Management**: weight-based artemisinin-based combination therapy; avoid drug interactions with ART (esp. protease inhibitors). * **Prophylaxis**: OI prophylaxis not indicated by CD4; but TMP-SMX (if used for PCP) also offers some antimalarial effect; use bed nets and vector control. --- ### Case 22 – STI coinfection increasing HIV transmission 25-year-old MSM with HIV (CD4 450, suppressed VL) but presents with painful genital ulcers; T. pallidum positive (syphilis). * **Management**: benzathine penicillin G; partner notification; risk-reduction counselling. * **Prophylaxis angle**: Although not an OI, treating STIs reduces genital inflammation and HIV transmission risk – a form of **secondary prevention** in public health terms. --- ### Case 23 – Recurrent herpes simplex HIV+ patient, CD4 90, recurrent painful genital ulcers, HSV PCR positive. * **Management**: oral acyclovir/valacyclovir treatment; consider chronic suppressive therapy. * **Prophylaxis**: suppressive acyclovir doesn’t prevent classic “AIDS-defining OIs,” but it reduces HSV recurrences; TMP-SMX still required for PCP/TE prophylaxis. --- ### Case 24 – Post-OI CD4 recovery and stopping prophylaxis Patient with prior PCP and TE, now on ART with CD4 260 for 1 year, VL undetectable; still on TMP-SMX DS OD and secondary TE regimen. * **Question**: can prophylaxis be stopped? * **Answer**: Yes – CD4 >200 for >3–6 months with VL suppressed → both PCP and TE prophylaxis can be safely discontinued. ([bccfe.ca][16]) --- ### Case 25 – Poor adherence and recurrent OIs HIV+ man with history of PCP and cryptococcal meningitis, frequently stops ART, CD4 fluctuates 40–250, now off ART and prophylaxis, presents with headache and cough. * **Risk**: relapse of cryptococcal disease or new PCP. * **Management**: full re-evaluation (LP, imaging, sputum/BAL); treat any active OI; intensive adherence counselling; involve psychosocial support. * **Prophylaxis**: restart secondary prophylaxis (fluconazole, TMP-SMX) and ART; emphasize that stopping drugs abruptly is dangerous; consider DOT/adherence aids. --- If you want, next I can: * Turn this into a **single-page high-yield PDF-style note layout**, or * Create **HTML + CSS + JS** sheet with these 25 cases as clickable cards (good for your ErrorOn/NEETPG sites). [1]: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/prophylaxis-prevent-first-episode?utm_source=chatgpt.com "Drug Therapies to Prevent First Episode of Opportunistic ..." [2]: https://www.cdc.gov/mmwr/pdf/rr/rr58e324.pdf?utm_source=chatgpt.com "Guidelines for Prevention and Treatment of Opportunistic ..." [3]: https://naco.gov.in/sites/default/files/7-Guidelines%20for%20Prevention%20and%20Management%20of%20common%20opportunistic%20infections.pdf?utm_source=chatgpt.com "Guidelines for Prevention and Management of Common ..." [4]: https://journals.asm.org/doi/10.1128/cmr.00101-22?utm_source=chatgpt.com "Pneumocystis jirovecii pneumonia in people living with HIV" [5]: https://www.uptodate.com/contents/toxoplasmosis-in-patients-with-hiv?utm_source=chatgpt.com "Toxoplasmosis in patients with HIV - UpToDate" [6]: https://journals.asm.org/doi/10.1128/cmr.00156-22?utm_source=chatgpt.com "Diagnosis and management of cryptococcal meningitis in HIV ..." [7]: https://bhiva.org/wp-content/uploads/2024/11/-file-SwhaEzgXmAGOt-hiv_v12_is2_Iss2Press_Text.pdf?utm_source=chatgpt.com "hiv medicine" [8]: https://www.nhstaysideadtc.scot.nhs.uk/Antibiotic%20site/pdf%20docs/Opportunistic%20infections.pdf?utm_source=chatgpt.com "Opportunistic infections.pdf" [9]: https://emedicine.medscape.com/article/1167298-overview?utm_source=chatgpt.com "CNS Toxoplasmosis in HIV: Overview, Pathophysiology ..." [10]: https://nhm.gov.in/images/pdf/guidelines/nrhm-guidelines/stg/hiv-opportunistic-infections.pdf?utm_source=chatgpt.com "hiv: opportunistic infections" [11]: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/pneumocystis?utm_source=chatgpt.com "Pneumocystis Pneumonia: Adult and Adolescent OIs | NIH" [12]: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/toxoplasmosis?utm_source=chatgpt.com "Toxoplasma gondii Encephalitis: Adult and Adolescent OIs" [13]: https://www.nejm.org/doi/full/10.1056/NEJMoa1110404?utm_source=chatgpt.com "Combination Antifungal Therapy for Cryptococcal Meningitis" [14]: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2823%2900731-4/abstract?utm_source=chatgpt.com "Global guideline for the diagnosis and management of ..." [15]: https://bccfe.ca/wp-content/uploads/2024/04/bc-cfe_therapeutic_guidelines_for_opportunistic_infections-pcp-mar-2023_nov8.pdf?utm_source=chatgpt.com "Pneumocystis pneumonia (PCP)" [16]: https://bccfe.ca/wp-content/uploads/2024/04/bc-cfe_therapeutic_guidelines_for_opportunistic_infections-toxoplasmosis.pdf?utm_source=chatgpt.com "toxoplasmosis" [17]: https://www.hiv.uw.edu/pdf/co-occurring-conditions/opportunistic-infections-prevention/core-concept/all?utm_source=chatgpt.com "Opportunistic Infections: Prevention - Core Concepts" [18]: https://bccfe.ca/wp-content/uploads/2024/04/bc-cfe_cryptococcosis_guidelines_oct2023.pdf?utm_source=chatgpt.com "Cryptococcosis" [19]: https://aahivm.org/clinical-research-update-040419/?utm_source=chatgpt.com "Clinical Research Update 4.4.19" [20]: https://www.ncbi.nlm.nih.gov/books/NBK531442/?utm_source=chatgpt.com "Key Recommendations, Rationale and Evidence Summary"