Eduovisual
Immune System
HIV: opportunistic infection prophylaxis by CD4 count
— Outpatient HIV care is a CCS staple: you must order CD4, viral load, and start/stop prophylaxis at the right thresholds.
— Missing prophylaxis is a common distractor "wrong answer" — and so is continuing prophylaxis indefinitely after immune reconstitution.
— Newly diagnosed HIV at any CD4 → screen and stratify immediately.
— Established HIV with falling CD4, ART nonadherence, or virologic failure.
— Patient presenting with constitutional symptoms (fever, weight loss, thrush, chronic diarrhea) — check CD4 before assuming OI.
— Pregnancy, new TB exposure, travel, or new pet exposure (cats → toxoplasmosis reactivation risk).
— CD4 <200 → start Pneumocystis jirovecii (PJP) prophylaxis.
— CD4 <150 + endemic exposure → consider histoplasmosis prophylaxis.
— CD4 <100 → start toxoplasmosis prophylaxis (if Toxo IgG+).
— CD4 <50 → start Mycobacterium avium complex (MAC) prophylaxis only if ART will be delayed; routine MAC ppx is no longer recommended if effective ART is started promptly.
— Always check CD4 and percentage; absolute number can mislead in lymphopenia or leukocytosis.
— Start ART early — ART itself is the most powerful "prophylaxis."
— Discontinue OI prophylaxis once CD4 is sustainably above threshold (usually >3–6 months) on suppressive ART.
Step 3 management: On a CCS case, the first three orders for any newly diagnosed PWH are CD4 count, HIV RNA viral load, and HIV genotype — then add prophylaxis and ART based on results.
— Date of HIV diagnosis, nadir CD4, current CD4 and viral load.
— ART regimen, adherence, prior virologic failures, resistance testing.
— Prior OIs (PJP, toxoplasmosis, cryptococcosis, MAC, CMV, TB) — these mandate secondary prophylaxis until immune reconstitution.
— Allergies, especially sulfa allergy (alters PJP/Toxo prophylaxis choice).
— Pregnancy status and intent.
— TB exposure, travel (Mississippi/Ohio valleys → histo; SW US → cocci), incarceration, homelessness.
— Vaccination history (pneumococcal, HBV, HPV, influenza, COVID, zoster, meningococcal in MSM).
— CD4 >500: Generally asymptomatic; bacterial infections, TB, HSV/VZV, candidal vaginitis.
— CD4 200–500: Thrush, oral hairy leukoplakia, recurrent bacterial pneumonia, Kaposi sarcoma, TB reactivation.
— CD4 <200: PJP (subacute dyspnea, dry cough, exertional desaturation), esophageal candidiasis (odynophagia).
— CD4 <100: Toxoplasmosis (ring-enhancing brain lesions, focal deficits), cryptococcal meningitis (subacute headache, low-grade fever), HIV wasting.
— CD4 <50: MAC (fever, night sweats, weight loss, diarrhea, elevated alk phos), CMV retinitis (floaters, painless vision loss), CMV colitis/esophagitis, PML (JC virus).
— "Cottage cheese plaques" + odynophagia → esophageal candidiasis (treat, also signals CD4 <200).
— "Floaters and visual field loss" in advanced HIV → CMV retinitis until proven otherwise.
— "Chronic watery diarrhea" → Cryptosporidium, microsporidia, MAC, CMV.
Board pearl: A previously well-controlled PWH who stops ART can drop CD4 rapidly within weeks — always re-check CD4 when adherence lapses rather than relying on the last value.
— Vitals: Fever pattern, tachypnea, resting SpO2, and—critically—ambulatory pulse oximetry (desaturation with walking is classic for PJP).
— General: Cachexia, temporal wasting → advanced disease, low CD4.
— HEENT:
– Oropharyngeal thrush (pseudomembranous white plaques scraping off) → marker for CD4 <200–300.
– Oral hairy leukoplakia (lateral tongue, EBV) → does not scrape off.
– Kaposi sarcoma lesions on palate/gingiva.
– Fundoscopy: "Pizza-pie" hemorrhages + fluffy white exudates → CMV retinitis (CD4 <50).
— Lymph nodes: Generalized lymphadenopathy; asymmetric/bulky nodes → consider TB, lymphoma, MAC.
— Pulmonary: Often unremarkable in PJP despite hypoxia (classic "exam-imaging dissociation"); focal consolidation suggests bacterial pneumonia or TB.
— Abdomen: Hepatosplenomegaly → MAC, disseminated histoplasmosis, lymphoma.
— Neuro: Focal deficits → toxoplasmosis, PML, CNS lymphoma; meningismus often absent in cryptococcal meningitis—headache and altered mentation dominate.
— Skin: Molluscum (large, central umbilication), seborrheic dermatitis, KS plaques, dermatomal zoster (can occur at any CD4).
— Sepsis from bacteremia (especially Salmonella, S. pneumoniae) — check lactate, MAP.
— Adrenal insufficiency in disseminated CMV, TB, or histoplasmosis → orthostasis, hyponatremia.
— Severe PJP can require ICU-level support; A-a gradient and PaO2 guide steroid use.
Key distinction: Thrush + CD4 <200 → PJP prophylaxis indicated even if the patient feels well. Oral hairy leukoplakia by itself doesn't trigger PJP prophylaxis — it's the CD4 number that drives the order, not the lesion.
— CD4 count and CD4% — drives prophylaxis decisions.
— HIV RNA viral load — drives ART urgency, monitors response.
— HIV genotype (resistance testing) before/at ART start.
— CBC, CMP — baseline cytopenias, renal/hepatic function for drug dosing.
— Fasting lipids, A1c — metabolic baseline before ART.
— Hepatitis serologies: HAV total, HBsAg/anti-HBs/anti-HBc, anti-HCV (with HCV RNA if positive).
— Syphilis (RPR or treponemal), gonorrhea/chlamydia (urine, rectal, pharyngeal as appropriate).
— Toxoplasma IgG — positive serology + CD4 <100 = start TMP-SMX for toxo prophylaxis.
— CMV IgG, VZV IgG, measles/rubella IgG — guide vaccination and risk counseling.
— TB screening: IGRA preferred (or TST); if positive and active TB ruled out → treat latent TB.
— G6PD level if dapsone or primaquine may be needed.
— Pregnancy test in people who can become pregnant.
— Urinalysis — proteinuria suggests HIVAN, also baseline for TDF.
— HLA-B*5701 if abacavir is being considered.
— CD4 every 3–6 months until stable >300 for ≥2 years on suppressive ART, then optional.
— Viral load every 3 months until suppressed, then every 6 months.
— Suspected PJP: CXR (diffuse bilateral interstitial infiltrates), LDH (elevated), beta-D-glucan, ABG/A-a gradient.
— Suspected cryptococcal disease: serum cryptococcal antigen (CrAg) screening recommended if CD4 <100 (some guidelines <200).
Step 3 management: On CCS, after starting prophylaxis, schedule a 2–4 week follow-up visit for ART tolerance, adherence, and adverse-effect screening — don't just say "follow up in 3 months."
— Induced sputum or bronchoalveolar lavage with immunofluorescence/PCR for P. jirovecii.
— Serum beta-D-glucan sensitive but nonspecific; LDH >500 supports diagnosis.
— HRCT chest if CXR equivocal: ground-glass opacities, pneumatoceles.
— MRI brain with contrast: multiple ring-enhancing lesions at gray-white junction and basal ganglia.
— Empiric pyrimethamine + sulfadiazine + leucovorin trial; clinical/imaging response within 10–14 days confirms.
— If no response → brain biopsy to rule out primary CNS lymphoma (single periventricular lesion, EBV PCR + in CSF, thallium SPECT positive).
— Serum CrAg screening at CD4 <100 (preemptive treatment if positive even when asymptomatic).
— LP with opening pressure (often >25 cm H2O), CSF CrAg, India ink, fungal culture.
— Blood cultures using mycobacterial bottles (AFB cultures); bone marrow or lymph node biopsy if persistently bacteremic with normal blood cultures.
— Elevated alkaline phosphatase and anemia are clues.
— Dilated ophthalmologic exam — retinitis is a clinical diagnosis.
— CMV PCR (quantitative) and tissue biopsy for colitis/esophagitis.
— Sputum AFB smear, culture, NAAT (e.g., Xpert MTB/RIF); CXR; consider extrapulmonary sampling.
— In HIV, CXR may be atypical (lower lobe, miliary, or normal) — low threshold to test.
Board pearl: A single ring-enhancing brain lesion + EBV PCR positive in CSF in a PWH = primary CNS lymphoma, not toxoplasmosis — biopsy, don't just empirically treat for Toxo.
— CD4 <200 cells/µL (or CD4% <14, or oropharyngeal candidiasis, or AIDS-defining illness):
– PJP primary prophylaxis indicated.
— CD4 <150 + residence/travel in hyperendemic area (e.g., parts of Midwest):
– Consider itraconazole for histoplasmosis prophylaxis (rare on boards but classic).
— CD4 <100 + Toxoplasma IgG positive:
– Toxoplasmosis primary prophylaxis (TMP-SMX double-strength daily covers both PJP and Toxo).
— CD4 <50:
– MAC primary prophylaxis with azithromycin 1200 mg weekly only if effective ART will not be initiated promptly. Current US guidelines: routine MAC ppx not recommended when ART starts immediately and is virologically effective.
– Increase vigilance for CMV (no routine ppx; screen with dilated eye exams every 3–6 months if very low CD4).
— PJP: CD4 >200 for >3 months on ART.
— Toxoplasmosis: CD4 >200 for >6 months and completed initial therapy.
— Cryptococcus: CD4 >100 for >3 months, completed therapy, asymptomatic.
— MAC: ≥12 months treatment + CD4 >100 for >6 months on ART.
— CMV retinitis: CD4 >100 for >3–6 months + inactive lesion (ophtho clearance).
— ART itself reduces OI risk more than any single prophylactic drug.
— Stop prophylaxis only when CD4 has been sustainably above threshold.
Step 3 management: When CD4 crosses a threshold downward (e.g., 220 → 180), start prophylaxis at the next visit's confirmation or immediately if the drop is consistent with clinical context — don't wait for symptoms.
— First line: TMP-SMX 1 DS tab daily (or 1 SS daily; or 1 DS three times weekly).
— Covers PJP + Toxoplasma + many bacterial respiratory pathogens + Nocardia + some Listeria.
— Alternatives (sulfa allergy/intolerance):
– Dapsone 100 mg daily (check G6PD first; doesn't cover Toxo at this dose).
– Dapsone 50 mg + pyrimethamine 50 mg weekly + leucovorin → covers Toxo too.
– Atovaquone 1500 mg daily with food (well tolerated, expensive).
– Aerosolized pentamidine 300 mg monthly (last line; no Toxo coverage, risk of apical disease/extrapulmonary PJP).
— First line: TMP-SMX 1 DS daily (same pill as PJP).
— Alternatives: dapsone + pyrimethamine + leucovorin; atovaquone ± pyrimethamine.
— Azithromycin 1200 mg weekly (preferred; few interactions, once-weekly).
— Alternatives: clarithromycin 500 mg BID (many drug interactions), rifabutin (drug interactions, requires TB rule-out first).
— Rule out active MAC disease with blood cultures before starting prophylaxis.
Board pearl: TMP-SMX 1 DS daily is the single highest-yield prophylaxis answer in HIV — it knocks out PJP and Toxo simultaneously and is the default unless the patient has a true sulfa allergy.
— AEs: Rash (including SJS/TEN), hyperkalemia, hyponatremia, marrow suppression, transaminitis, crystalluria, AIN.
— Drug interactions: Warfarin (↑INR), methotrexate, ACEi/ARB + spironolactone (hyperkalemia), sulfonylureas.
— Mild reaction (rash, low fever): consider rechallenge or desensitization — preferred over abandoning TMP-SMX given its dual coverage.
— Avoid in late pregnancy (third trimester → kernicterus risk); folate antagonism is a concern in first trimester — give folic acid supplementation.
— AEs: Hemolytic anemia (esp. G6PD deficiency), methemoglobinemia (cyanosis with normal PaO2, chocolate-brown blood), agranulocytosis, hypersensitivity.
— Always check G6PD before starting.
— Well tolerated; GI upset; must be taken with fatty food for absorption. Expensive.
— Marrow suppression — always co-administer leucovorin (folinic acid).
— QT prolongation; GI upset; generally few interactions — preferred over clarithromycin.
— Strong CYP3A4 inhibitor — major interactions with protease inhibitors, statins, ergots.
— Potent CYP inducers — reduce levels of many ARTs (especially PIs, some INSTIs). Use rifabutin rather than rifampin when possible in PWH on ART.
— Uveitis, orange body fluids, hepatotoxicity.
— Sulfa rash → desensitize TMP-SMX first; if unable, dapsone (after G6PD) > atovaquone.
— Stop prophylaxis when CD4 thresholds met for required duration on suppressive ART.
Step 3 management: A PWH on TMP-SMX who develops a mild morbilliform rash without mucosal involvement → hold, treat symptoms, then desensitize, not lifelong switch.
— Slower CD4 recovery on ART; OI risk persists longer at borderline CD4 counts.
— Higher rates of comorbid CKD, CVD, osteoporosis, polypharmacy → drug interactions matter.
— Maintain prophylaxis thresholds the same, but be vigilant for TMP-SMX-induced hyperkalemia if also on ACEi/ARB/spironolactone.
— Vaccinations: PCV20 (or PCV15 + PPSV23), zoster (recombinant, even <50 if HIV), influenza annually, COVID boosters, Tdap, HBV.
— TMP-SMX: Reduce dose at CrCl <30 (often 1 SS daily or DS three times weekly); avoid if CrCl <15 unless dialysis-adjusted.
— Monitor potassium and creatinine 1–2 weeks after starting — TMP competes with creatinine secretion (↑Cr without true GFR drop) and inhibits ENaC (hyperkalemia).
— Tenofovir disoproxil (TDF): nephrotoxic; switch to TAF if CrCl declining or proteinuria/Fanconi syndrome.
— Atovaquone, dapsone, azithromycin: generally safe in renal impairment.
— TMP-SMX, dapsone, rifabutin — all hepatotoxic; monitor LFTs.
— Coinfection with HBV — tenofovir-based ART covers both; never stop abruptly (HBV flare).
— HCV coinfection — treat with DAAs; check ART interactions (especially with PIs).
— Clarithromycin + statins → rhabdomyolysis.
— Rifabutin + INSTI/PI → adjust ART doses.
— Azoles (fluconazole, itraconazole) + many ARTs → QT, levels.
Key distinction: A rising creatinine on TMP-SMX is often competitive inhibition of tubular Cr secretion, not true AKI — check cystatin C or urinalysis (bland sediment) before discontinuing prophylaxis unnecessarily.
— Goal: Maintain viral suppression to prevent perinatal transmission (<1% if suppressed at delivery).
— PJP prophylaxis: Same CD4 threshold (<200). TMP-SMX is preferred; concerns about first-trimester folate antagonism (neural tube defects) → supplement folic acid 0.4–0.8 mg daily (some give higher). Avoid near term (kernicterus risk).
– Alternative: atovaquone or aerosolized pentamidine in first trimester if concerned.
— Toxo ppx: TMP-SMX. Pyrimethamine generally avoided in first trimester.
— MAC ppx: Azithromycin preferred over clarithromycin (clarithro teratogenic in animals).
— TB: Treat latent TB; INH + pyridoxine acceptable in pregnancy.
— Intrapartum IV zidovudine if VL >1000 at delivery; scheduled cesarean at 38 weeks if VL >1000.
— Infant: 4–6 weeks zidovudine (or combination ART regimen if high risk); avoid breastfeeding in US (formula recommended, though shared decision-making is now accepted with suppressed VL).
— CD4 percentage is more reliable than absolute count in young children.
— PJP prophylaxis universal from 4–6 weeks to 12 months of age in HIV-exposed infants until HIV is excluded; continue throughout first year if HIV-infected regardless of CD4.
— After age 1, use CD4%/count thresholds (age-adjusted).
— Live vaccines (MMR, varicella) allowed if CD4% ≥15% and not severely immunosuppressed; avoid in severe immunosuppression.
Board pearl: Every HIV-exposed infant in the US gets PJP prophylaxis starting at 4–6 weeks until HIV is definitively excluded — this is independent of maternal CD4 or viral load.
— Reassess adherence, drug interactions, malabsorption (atovaquone needs fat), and actual CD4.
— Breakthrough PJP on aerosolized pentamidine often presents with apical or extrapulmonary disease.
— Resistance is uncommon but possible (e.g., DHPS mutations in P. jirovecii).
— Paradoxical worsening of a known OI or unmasking of a subclinical OI within weeks–months of ART initiation, as CD4 recovers.
— Highest risk: low baseline CD4 (<50), rapid VL drop, active untreated OI at ART start.
— Common culprits: TB, cryptococcus, MAC, CMV, PML, KS.
— Management: Continue ART, treat the underlying OI, add corticosteroids for severe inflammation (especially TB-IRIS, PJP with hypoxia).
— TMP-SMX → SJS/TEN, hyperkalemia, AIN, marrow suppression.
— Dapsone → methemoglobinemia, hemolysis.
— Rifabutin → uveitis, neutropenia.
— Pyrimethamine → marrow suppression (use leucovorin).
— Clarithromycin/azoles ↑ INSTI/PI levels.
— Rifamycins ↓ ART levels — virologic failure, then rebound viremia, then CD4 drop → OI risk returns.
— Cardiovascular disease, CKD, neurocognitive disorders, non-AIDS malignancies dominate mortality in well-controlled PWH.
— Adjunctive prednisone if PaO2 <70 mmHg or A-a gradient >35 — reduces mortality.
CCS pearl: When starting ART in a patient with CD4 <50 and an active OI, treat the OI first for ~2 weeks (except for TB meningitis and cryptococcal meningitis, where ART is delayed further) to reduce IRIS risk — but don't delay ART beyond 2 weeks for most OIs.
— PJP with PaO2 <70 mmHg, A-a gradient >35, or respiratory distress → IV TMP-SMX + steroids; consider HDU/ICU.
— Cryptococcal meningitis → admit for induction therapy (liposomal amphotericin B + flucytosine) and serial LPs for ICP management.
— Suspected CNS toxoplasmosis with mass effect, seizures, or altered mentation.
— CMV retinitis threatening the macula or optic nerve → urgent ophthalmology + IV/intravitreal therapy.
— Disseminated histoplasmosis, severe MAC bacteremia, or sepsis from any source.
— Severe drug reactions: SJS/TEN, DRESS, hepatic failure.
— Mild–moderate PJP (PaO2 ≥70) on oral TMP-SMX with close follow-up.
— Asymptomatic CrAg-positive patients without CNS involvement (preemptive fluconazole, close monitoring).
— Stable patients starting prophylaxis at threshold CD4 counts.
— Infectious Disease/HIV specialist for every newly diagnosed patient, ART selection, OI treatment.
— Ophthalmology for any visual symptoms or routine screening at CD4 <50.
— Neurology/Neurosurgery for CNS lesions requiring biopsy.
— Pulmonology for bronchoscopy in suspected PJP without diagnostic sputum.
— OB for pregnant PWH (high-risk OB + ID co-management).
— Social work, case management, pharmacy — adherence is the #1 driver of outcomes.
— Discharge bundle: ART supply, prophylaxis prescription, follow-up within 1–2 weeks, CD4/VL recheck schedule, vaccination plan, partner notification resources, Ryan White program linkage if uninsured.
Step 3 management: Never discharge a PWH from the hospital after an OI without confirming a scheduled outpatient HIV clinic appointment — engagement in care is the single strongest predictor of survival.
— Bacterial pneumonia (S. pneumoniae, H. influenzae) — usually focal, more acute, productive cough.
— TB — upper lobe cavitation if CD4 >200; atypical/miliary/lower lobe if CD4 <200.
— CMV pneumonitis — rare without other CMV end-organ disease; CD4 <50.
— Histoplasmosis, coccidioidomycosis — endemic exposure history, diffuse nodular infiltrates.
— Kaposi sarcoma pulmonary involvement — endobronchial lesions, pleural effusions, KS elsewhere.
— Lymphoid interstitial pneumonitis — more in children with HIV.
— Toxoplasmosis — multiple lesions, basal ganglia/gray-white junction, Toxo IgG+, responds to empiric therapy.
— Primary CNS lymphoma — single periventricular lesion, EBV PCR+ in CSF, thallium SPECT uptake.
— Tuberculoma — TB history/exposure.
— Bacterial brain abscess — usually one cause/source identified.
— PML (JC virus) — non-enhancing white matter lesions, no mass effect; distinct from ring-enhancing differential but commonly tested alongside.
— Cryptosporidium, microsporidia, Isospora/Cystoisospora, MAC, CMV colitis, C. difficile.
— Candida (most common, treat empirically with fluconazole), CMV (large single ulcers), HSV (multiple small ulcers, vesicles).
— MAC, disseminated histoplasmosis, TB, CMV, lymphoma.
Key distinction: Empiric therapy for toxoplasmosis is appropriate for multiple ring-enhancing lesions with positive Toxo serology; a single lesion with negative Toxo serology should push you toward biopsy for CNS lymphoma.
— HIV itself: acute retroviral syndrome (mononucleosis-like), HIV-associated nephropathy (proteinuria, FSGS), HIV-associated neurocognitive disorder.
— Malignancies (AIDS-defining and non-AIDS):
– Kaposi sarcoma — violaceous skin/mucosal/visceral lesions; HHV-8.
– Non-Hodgkin lymphoma — B symptoms, masses, marrow involvement.
– Primary CNS lymphoma — see above.
– Cervical and anal cancer — HPV-driven; screen with Pap/anal cytology.
– Lung cancer, HCC, head and neck cancers — increased in PWH.
— Drug reactions:
– Abacavir hypersensitivity (HLA-B*5701) — fever, rash, GI, respiratory.
– Efavirenz — vivid dreams, neuropsychiatric symptoms; false-positive cannabinoid screens.
– Tenofovir — Fanconi, renal dysfunction, bone loss.
– Dolutegravir — weight gain, insomnia, possible neural tube defect signal (now considered minimal).
— Immune reconstitution inflammatory syndrome — paradoxical worsening with ART; not a new infection.
— Pulmonary embolism — PWH are hypercoagulable; consider in unexplained hypoxia.
— Heart failure / cardiomyopathy — HIV cardiomyopathy, ART-related dyslipidemia, accelerated atherosclerosis.
— Endocrine: adrenal insufficiency (CMV/TB adrenalitis, ketoconazole, etomidate); hypogonadism.
— Think MAC, TB, lymphoma — biopsy is often necessary; don't just empirically treat infection.
Board pearl: A PWH with dyspnea and hypoxia but a clear CXR could be PJP (early), PE, or anemia — order ambulatory SpO2, D-dimer/CT-PA if appropriate, and CBC, not just a chest X-ray repeat.
— Continue induction/consolidation therapy as required (e.g., toxo 6 weeks total, crypto: amphoB+flucytosine 2 weeks → fluconazole 8 weeks → maintenance).
— Initiate or continue ART — timing depends on OI (most OIs: start within 2 weeks; TB meningitis and crypto meningitis: delay 4–8 weeks to reduce IRIS mortality).
— Secondary prophylaxis (chronic maintenance) at the regimens above until CD4 thresholds met.
— Primary prophylaxis for any threshold the patient still meets.
— Sustained CD4 above threshold for the required duration.
— Suppressed viral load on stable ART.
— Resolution of acute OI (for secondary ppx).
— If CD4 falls below threshold again → restart prophylaxis.
— PCV20 once (or PCV15 followed by PPSV23 ≥8 weeks later, then PPSV23 booster at 5 years).
— Influenza annually (inactivated).
— Tdap, then Td every 10 years.
— HBV series (use higher-dose or 3-dose Heplisav-B; check anti-HBs).
— HPV through age 26 (consider through 45 shared decision).
— Recombinant zoster (Shingrix) regardless of age in PWH ≥18.
— MenACWY for MSM and other risk groups; MenB per shared decision.
— COVID-19 per current schedule.
— MMR, varicella only if CD4 >200 and nonimmune.
— Condoms, PrEP partners, treatment-as-prevention (U=U).
— Screen STIs every 3–6 months in high-risk patients.
— Cancer screening: cervical, anal, lung (if criteria met), colorectal, breast.
Step 3 management: Document the exact CD4 trigger for stopping each prophylaxis in the chart so cross-covering clinicians don't continue meds unnecessarily — this is a Step 3-favored quality/safety move.
— At ART start / change: Visit at 2–4 weeks for tolerance/adherence; labs at 4–8 weeks (VL, CMP, CBC).
— First 6 months: VL and CD4 every 3 months.
— Suppressed and stable >2 years, CD4 >300: VL every 6 months; CD4 monitoring optional.
— Annual: fasting lipids, A1c (or every 6 months on PI/INSTI), UA, renal function, STI screen, TB screen if exposure changes.
— TMP-SMX: CBC, K+, Cr at 2 weeks, then every 3–6 months.
— Dapsone: CBC, methemoglobin if symptomatic; G6PD at baseline.
— Azithromycin: ECG if other QT-prolonging drugs; LFTs if symptomatic.
— Rifabutin: CBC, LFTs, eye symptoms (uveitis).
— Adherence — single biggest determinant of outcomes; address barriers (housing, mental health, substance use).
— U = U (undetectable = untransmittable): suppressed viral load means no sexual transmission.
— Disclosure to partners; PrEP for HIV-negative partners.
— Safer-sex counseling, contraception, preconception planning.
— Substance use, tobacco, alcohol screening with brief intervention.
— Mental health — depression screen (PHQ-9), anxiety, trauma history.
— Bone health (DEXA at 50, or earlier if on TDF/risk factors).
— Cardiovascular risk reduction (statin per AHA/ACC, including REPRIEVE-supported primary prevention statin in PWH 40–75 with low-moderate ASCVD risk).
— Vaccinations as above.
CCS pearl: On a CCS HIV case, after stabilizing the acute issue, the closing orders should always include "HIV clinic follow-up in 2–4 weeks", "adherence counseling", and "partner notification/testing" — the simulation rewards longitudinal thinking.
— HIV status is protected health information; sharing requires explicit consent except where mandated.
— Partner notification: All US states have mechanisms (often via the health department) — physicians should encourage patient-led disclosure, offer assisted notification, and know local laws. Some states permit physician notification of identifiable partners without consent if the patient refuses and risk is ongoing — know that the preferred route is patient-led or public health–assisted, not direct physician disclosure.
— Mandatory reporting of HIV diagnosis to public health is required in all US states.
— Opt-out HIV testing is recommended for all patients 13–64 annually in healthcare settings; explicit written consent is not required federally, but state laws vary.
— Pregnant patients: opt-out testing at first prenatal visit and again in the third trimester in high-prevalence areas.
— Address cognitive impairment (HIV-associated neurocognitive disorder, substance use) before assuming nonadherence is volitional.
— Use directly observed therapy or long-acting injectable ART (cabotegravir/rilpivirine) when adherence is a barrier.
— Address structural barriers — housing instability, insurance, transportation. Link to Ryan White and ADAP programs.
— Medication reconciliation at every transition — prophylaxis and ART are commonly missed on admission/discharge.
— Avoid prescribing interacting medications (e.g., rifampin with INSTIs, simvastatin with PIs, PPIs with rilpivirine).
— Needle-stick exposure in healthcare workers: start PEP (tenofovir/emtricitabine + dolutegravir or raltegravir) within hours, ideally <72 h, continue 28 days, baseline and follow-up HIV testing at 6 weeks, 3 months, and 4–6 months.
Board pearl: A patient who refuses to inform partners and continues unprotected sex creates an ethical obligation to involve public health partner-notification services — not to override confidentiality unilaterally as the first step.
— <500: bacterial pneumonia, TB, HSV/VZV, oral candida.
— <200: PJP (start TMP-SMX), esophageal candidiasis, KS.
— <150: histoplasmosis (endemic areas).
— <100: toxoplasmosis (if IgG+), cryptococcal meningitis, chronic cryptosporidiosis.
— <50: MAC (if ART delayed), CMV retinitis/colitis, PML, primary CNS lymphoma.
— PJP ppx → TMP-SMX (also covers Toxo).
— PJP treatment → TMP-SMX + steroids if PaO2 <70.
— Toxo treatment → pyrimethamine + sulfadiazine + leucovorin.
— Cryptococcal meningitis induction → liposomal amphotericin B + flucytosine.
— MAC treatment → clarithromycin (or azithromycin) + ethambutol ± rifabutin.
— CMV retinitis → IV ganciclovir or oral valganciclovir ± intravitreal.
— Latent TB → INH 9 mo or 3HP (12-week INH/rifapentine).
— Esophageal candidiasis → fluconazole.
— G6PD before dapsone or primaquine.
— Toxo IgG at baseline (drives ppx decisions).
— Serum CrAg if CD4 <100.
— HLA-B*5701 before abacavir.
— "Pizza-pie fundus" → CMV retinitis.
— "Soap-bubble lesions in brain" → cryptococcoma (or toxoplasmosis).
— "Owl-eye inclusions" → CMV.
— "Cottage cheese plaques" → oral candidiasis.
— "Ground-glass opacities, elevated LDH, exertional desaturation" → PJP.
— "Floaters, painless vision loss" → CMV retinitis.
Board pearl: Whenever a stem mentions a specific CD4 number, first decide which OIs the patient is at risk for and whether prophylaxis is indicated — half the question is usually a prophylaxis decision.
— Newly diagnosed HIV with CD4 180; next step? → Start TMP-SMX for PJP prophylaxis and initiate ART.
— CD4 80, Toxo IgG+; patient already on TMP-SMX DS daily → no additional drug needed (TMP-SMX already covers Toxo).
— PJP ppx needed, prior anaphylaxis to sulfa → check G6PD → dapsone (or atovaquone if G6PD-deficient). If a mild prior rash → desensitize TMP-SMX.
— Patient on TMP-SMX for 2 years, now CD4 350 sustained >6 months with suppressed VL → discontinue PJP prophylaxis.
— Patient stopped ART, CD4 drops from 400 → 150 → restart PJP ppx now.
— CD4 30, started on effective ART today → routine MAC ppx not indicated (per current guidelines). Older question banks may still favor azithromycin — know both.
— Two weeks after starting ART, patient develops new lymphadenopathy/fever → IRIS; continue ART, treat OI, consider steroids.
— Pregnant PWH at first visit, CD4 150 → start TMP-SMX (with folate), start ART regardless of CD4.
— Multiple ring-enhancing lesions + Toxo IgG+ → empiric pyrimethamine/sulfadiazine. Single lesion or no improvement at 2 weeks → biopsy for CNS lymphoma.
— CD4 30 + floaters → urgent dilated fundoscopy → CMV retinitis → valganciclovir.
Step 3 management: The "next best step" in HIV stems is almost always either (a) check the CD4/VL, (b) start the appropriate prophylaxis at the threshold, or (c) start/optimize ART — pick whichever the stem hasn't already done.
In people with HIV, opportunistic infection prophylaxis is driven by CD4 thresholds: start TMP-SMX at CD4 <200 (covers PJP and—if Toxo IgG+ at CD4 <100—toxoplasmosis), consider MAC prophylaxis with weekly azithromycin only at CD4 <50 when effective ART is delayed, and discontinue each prophylaxis once CD4 is sustainably above its threshold on suppressive ART.
Board pearl: When in doubt on a Step 3 HIV stem, the answer is almost always "start ART and start TMP-SMX" if CD4 is under 200 — the rest is fine-tuning.