217.1 🎓 醫學生版

217.1.0.1 📌 一頁重點

217.1.0.1.1 When to Start ART

• Universal: ALL HIV+ regardless of CD4 (DHHS, WHO, IAS-USA)
• Start ASAP after diagnosis (rapid initiation, even same-day in many programs)
• Benefits:
  • Reduces mortality
  • Prevents OIs
  • Prevents transmission (U=U)
  • Reduces non-AIDS complications
  • Better outcomes if started early

217.1.0.1.2 First-Line Regimens (DHHS 2024)

217.1.0.1.2.1 InSTI + 2 NRTIs (Preferred)

• Bictegravir/Tenofovir Alafenamide/Emtricitabine (Biktarvy) — single tablet daily; preferred for most
• Dolutegravir + (TDF or TAF)/Emtricitabine — preferred for pregnancy (DTG + TDF/FTC; Tivicay + Truvada)
• Dolutegravir/Lamivudine (Dovato) — 2-drug regimen, alternative

217.1.0.1.2.2 Long-Acting Injectable

• Cabotegravir + Rilpivirine (Cabenuva) — IM monthly or every 2 months; for virally suppressed switching
• Lenacapavir (2025 expanding) + cabotegravir/rilpivirine in selected

217.1.0.1.3 Backbone Components

217.1.0.1.3.1 NRTIs (Nucleoside Reverse Transcriptase Inhibitors)

• TAF (tenofovir alafenamide): less renal + bone toxic than TDF
• TDF (tenofovir disoproxil fumarate): HBV co-treatment when needed
• FTC (emtricitabine) + 3TC (lamivudine): similar, HBV active
• ABC (abacavir): HLA-B*5701 screening before (hypersensitivity)
• AZT (zidovudine): older, marrow suppression

217.1.0.1.3.2 NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors)

• Doravirine — newer, fewer interactions
• Rilpivirine — used in long-acting Cabenuva
• Efavirenz — older, vivid dreams/psych, fewer interactions
• HIV-2 naturally resistant

217.1.0.1.3.3 PIs (Protease Inhibitors)

• Darunavir/cobicistat or ritonavir — boosted
• Atazanavir/cobicistat or ritonavir — boosted; hyperbilirubinemia
• Reserved for resistance + specific indications

217.1.0.1.3.4 InSTIs (Integrase Strand Transfer Inhibitors)

• Dolutegravir (DTG): high barrier, daily
• Bictegravir (BIC): similar; in Biktarvy
• Raltegravir (RAL): older, BID
• Elvitegravir/cobicistat: in some FDCs
• Cabotegravir (CAB): long-acting injectable

217.1.0.1.3.5 Entry Inhibitors

• Maraviroc: CCR5 antagonist; requires tropism testing
• Enfuvirtide (T-20): gp41 fusion; SC injection BID
• Ibalizumab: CD4 attachment mAb; IV q2 wk
• Fostemsavir: gp120 attachment; oral; salvage

217.1.0.1.3.6 Capsid Inhibitor

• Lenacapavir (Sunlenca): SC injection every 6 months; salvage + emerging PrEP

217.1.0.1.4 Treatment Monitoring

• HIV RNA viral load: at start, 4-8 wk, 24 wk, then q3-6 mo
• CD4 count: at start, q3-6 mo
• CBC, comprehensive metabolic panel, LFTs: at start + monitoring
• Lipids: baseline + monitoring (ART-related dyslipidemia)
• Resistance testing: at diagnosis, virologic failure
• **HLA-B*5701** before abacavir
• HBV + HCV screening: at start
• STDs: baseline + at least annually

217.1.0.1.5 Treatment Goals

• Virologic suppression (HIV RNA < 50 copies/mL) within 24 wk of ART start
• CD4 reconstitution (gradual, 50-100/yr)
• No drug toxicities
• U=U achieved

217.1.0.1.6 Drug Interactions (Critical)

• InSTIs + polyvalent cations (Ca, Mg, Al, Fe) — separate dosing
• PIs / cobicistat (CYP3A4 inhibitors) — many drug interactions (statins, anti-arrhythmics, anticoagulants, immunosuppressants, etc.)
• Rifampin induces — incompatible with most PIs; alt: rifabutin
• NNRTIs (efavirenz) induce — many interactions
• TDF + nephrotoxic drugs caution
• Liverpool HIV drug interactions tool for reference

217.1.0.1.7 PrEP (Pre-Exposure Prophylaxis)

• Truvada (TDF/FTC) daily — oral, classic
• Descovy (TAF/FTC) daily — oral, no renal/bone concerns
• Cabotegravir LA (Apretude) — IM injection every 2 months
• Lenacapavir LA — SC every 6 months (2025 trials; FDA expected)
• 2-1-1 dosing (event-based, Truvada) — for MSM; before + after exposure
• 2024 ACIP: routinely offer to all sexually active patients with risk factors
• Doxy-PEP adjunct (Ch 162) for STI prevention

217.1.0.1.8 Post-Exposure Prophylaxis (PEP)

• Within 72 hours of exposure
• 3-drug ART × 28 days
• TDF/FTC + raltegravir or dolutegravir (preferred)
• Source patient testing
• Follow-up HIV testing 4-6 wk + 3 mo

217.1.0.1.9 IRIS (Immune Reconstitution Inflammatory Syndrome)

• 10-30% of patients starting ART, especially low CD4
• Paradoxical worsening of opportunistic infection or other (TB, cryptococcal, KS, etc.)
• Treatment: continue ART + treat underlying + steroid sometimes

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217.1.0.2 1️⃣ When to Start ART

217.1.0.2.1 Universal Start (DHHS, IAS-USA, WHO)

• All HIV+ regardless of CD4 count
• Start ASAP after diagnosis
• “Rapid Start” or “Same-Day ART” programs
• Evidence: START + TEMPRANO trials (2015)
  • Mortality + morbidity reduction with early ART
  • Even at high CD4

217.1.0.2.2 Rapid Start / Same-Day ART

• Many programs initiate ART same day or within 7 days of HIV diagnosis
• Counseling + linkage to care + initial regimen
• Reduces loss to follow-up
• WHO recommendation

217.1.0.2.3 Pre-ART Workup

• HIV viral load + CD4
• HIV genotype resistance test
• CBC, CMP, LFTs, lipids
• HBV + HCV + syphilis + STDs
• HLA-B*5701 (if abacavir considered)
• Pregnancy test (if applicable)
• Vaccinations: hepatitis A + B if not immune, pneumococcal, flu, COVID, HPV, MMR (CD4 ≥ 200)

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217.1.0.3 2️⃣ First-Line Regimens (DHHS 2024)

217.1.0.3.1 Preferred for Most Patients

217.1.0.3.1.1 Biktarvy (Bictegravir/TAF/FTC)

• Single tablet daily
• High barrier to resistance
• Few drug interactions
• Suitable for most adults including pregnant (with caveats — see below)
• Preferred most patients

217.1.0.3.1.2 Dovato (Dolutegravir/Lamivudine)

• 2-drug regimen
• Daily single tablet
• For ART-naïve with VL < 500K, no HBV
• Reduces NRTI exposure long-term
• Alternative

217.1.0.3.1.3 Dolutegravir + Truvada (TDF/FTC) or Descovy (TAF/FTC)

• Separate pills
• Standard backbone + InSTI
• Pregnancy: DTG + TDF/FTC commonly used

217.1.0.3.2 Long-Acting Injectable

217.1.0.3.2.1 Cabenuva (Cabotegravir + Rilpivirine)

• IM injection monthly or every 2 months
• For virally suppressed switching from oral ART
• Not for treatment-naive (study ongoing)
• Convenience + adherence advantage
• ATLAS-2M trial: every-2-month dosing non-inferior to monthly

217.1.0.3.2.2 Lenacapavir + Cabotegravir/Rilpivirine

• Lenacapavir SC every 6 months
• Combination protocols emerging

217.1.0.3.3 Alternative Regimens (Specific Situations)

• Darunavir/cobicistat + TAF/FTC for resistance / specific scenarios
• Atazanavir/cobicistat + TAF/FTC for resistance
• Doravirine + TAF/3TC (Delstrigo) — NNRTI-based alternative

217.1.0.3.4 Pediatric

• Weight-based dosing
• Dolutegravir + 2 NRTIs commonly
• Pediatric formulations expanding

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217.1.0.4 3️⃣ Resistance Testing

217.1.0.4.1 When to Test

• At ART start (HIV genotype) — guides initial regimen
• Virologic failure (HIV RNA > 200 copies/mL on ART)
• Suboptimal response

217.1.0.4.2 Tests

• HIV genotype (most common): sequencing reverse transcriptase, protease, integrase
• HIV phenotype: actual viral susceptibility (rare clinical use)
• GenoSure Archive: tests proviral DNA (use in suppressed patients)

217.1.0.4.3 Common Resistance Mutations

• M184V: 3TC + FTC resistance; AZT/TDF/d4T re-sensitization paradoxically
• K65R: TDF + ABC + 3TC resistance
• K103N: NNRTI cross-resistance (efavirenz, nevirapine)
• Y181C: NNRTI resistance
• InSTI mutations: rare; G140S, Q148H, N155H
• PI mutations: I50V, V82A, L90M

217.1.0.4.4 Stewardship

• Don’t use single-drug therapy (selects resistance rapidly)
• Adherence support before regimen changes
• Drug interactions check

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217.1.0.5 4️⃣ Treatment Monitoring

217.1.0.5.1 Routine Schedule

Time	Tests
Baseline	HIV RNA, CD4, genotype, CBC, CMP, LFTs, lipids, HLA-B*5701 (if abacavir), HBV/HCV/syphilis/STDs, pregnancy
2-8 weeks after ART start	HIV RNA, CMP
24 weeks	HIV RNA (should be < 50 copies/mL) + CD4
Quarterly first year	HIV RNA, CD4, CMP, lipids
Annually (after stable)	HIV RNA + CD4 (q6 mo), CMP, lipids, STDs
Resistance test	At virologic failure

217.1.0.5.2 Virologic Failure Definition

• HIV RNA > 200 copies/mL on ART
• Investigate adherence + drug interactions + resistance
• Genotype test
• Switch regimen if resistance

217.1.0.5.3 CD4 Decay Despite Suppression

• Some patients fail to fully recover CD4 (immune non-responders)
• Even with virologic suppression
• Increases comorbidity risk
• Optimization: ART intensification (rare), exclude other causes (IFN-γ, etc.)

217.1.0.5.4 Long-Term Monitoring

• ART comorbidities: CVD, renal, bone, metabolic, neurocognitive
• Annual lipids, kidney function, bone density (DEXA)
• Cancer screening
• Depression, substance use

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217.1.0.6 5️⃣ Toxicities + Side Effects

217.1.0.6.1 TDF

• Renal: proximal tubulopathy, Fanconi syndrome
• Bone: BMD loss, fracture risk
• Monitor: Cr, urine protein, calcium

217.1.0.6.2 TAF

• Reduced renal + bone toxicity
• Lipids less favorable than TDF
• Weight gain (Biktarvy users)

217.1.0.6.3 ABC

• Hypersensitivity reaction (HLA-B*5701 screening)
• CVD risk debate

217.1.0.6.4 AZT

• Marrow suppression, lipoatrophy, mitochondrial toxicity
• Rarely used now

217.1.0.6.5 NNRTIs

• Efavirenz: CNS (vivid dreams, depression, suicidality)
• Rilpivirine: no neuropsych
• Doravirine: well-tolerated

217.1.0.6.6 PIs

• GI (diarrhea, nausea)
• Hyperlipidemia
• Insulin resistance
• Atazanavir hyperbilirubinemia (jaundice, cosmetic concern)
• Drug interactions

217.1.0.6.7 InSTIs

• Generally well-tolerated
• Weight gain
• Insomnia (cabotegravir)
• Headache (some)

217.1.0.6.8 Lipid + Metabolic

• ART-associated dyslipidemia
• Statins (with attention to interactions)
• Diet + exercise

217.1.0.6.9 Weight Gain

• TAF + INSTI combinations associated with significant weight gain
• Mechanism: combination effect
• Concerning for cardiometabolic
• Monitor + lifestyle

217.1.0.6.10 Bone Density

• TDF accelerates BMD loss
• TAF less
• DEXA + risk-based monitoring

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217.1.0.7 6️⃣ Drug Interactions

217.1.0.7.1 Major Considerations

217.1.0.7.1.1 InSTIs + Polyvalent Cations

• Ca, Mg, Al, Fe supplements / antacids
• Separate by 2-6 hours

217.1.0.7.1.2 PIs / Cobicistat (CYP3A4 Inhibitors)

• Many interactions:
  • Statins (simvastatin, lovastatin contraindicated)
  • Anti-arrhythmics (amiodarone — caution)
  • Anticoagulants (DOACs)
  • Immunosuppressants (tacrolimus dose adjusted)
  • Steroids (Cushingoid if inhaled)
  • Lurasidone, midazolam (contraindicated)
  • HIV / HCV drug interactions

217.1.0.7.1.3 NNRTIs (Efavirenz, Nevirapine) — Inducers

• Reduced levels of:
  • OCs (use barrier)
  • Methadone
  • Warfarin
  • Other ART drugs

217.1.0.7.1.4 Rifampin

• Major inducer
• Contraindicated with most PIs
• Alternative: rifabutin (for HIV-TB co-treatment)
• Compatible with DTG + EFV + double dose; ABC + Truvada generally OK

217.1.0.7.1.5 Acid Reducers

• PPIs / H2 blockers reduce atazanavir absorption
• Switch agent

217.1.0.7.1.6 Polypharmacy in Elderly HIV+

• Increasing elderly HIV+ on multiple medications
• Careful interaction review

217.1.0.8 7️⃣ Special Populations

217.1.0.8.1 Pregnancy

• All pregnant HIV+ → ART
• DTG + TDF/FTC preferred for new ART start in pregnancy
• DTG previously had concern about neural tube defects (Tsepamo) — later studies show low risk, now standard
• Biktarvy (BIC/TAF/FTC) alternative pregnancy data accumulating
• Avoid efavirenz 1st trimester (older concern about NTDs; not contraindicated now per WHO)
• Stop nevirapine in pregnancy if newly starting (hepatotoxicity risk)
• Monitor maternal viral load + CD4
• Infant ART prophylaxis 4-6 wk post-delivery
• Avoid breastfeeding in resource-rich; breastfeed + maternal ART in resource-limited

217.1.0.8.2 HBV Co-Infection

• Use HBV-active ART (TDF/TAF + emtricitabine OR 3TC) — single regimen treats both
• Don’t stop HBV-active drugs without alternative HBV treatment
• Monitor for flare on discontinuation

217.1.0.8.3 HCV Co-Infection

• Treat HCV with DAAs (Mavyret, Epclusa)
• Check drug interactions
• HCV cure improves multi-comorbidity

217.1.0.8.4 Renal Failure / Hemodialysis

• TDF avoided; use TAF
• ABC + RAL preferred
• Avoid nephrotoxic combinations

217.1.0.8.5 Hepatic Failure

• PIs caution
• Lamivudine + TDF + RAL preferred
• HCV cure first if possible

217.1.0.8.6 Older Adult HIV+

• Polypharmacy
• Cardiovascular + renal + bone + neuro comorbidities
• ART tolerance varies
• TDF vs TAF for bone / kidney

217.1.0.8.7 Pediatric HIV

• Weight-based dosing
• Liquid + chewable formulations
• DTG + 2 NRTIs preferred
• Pediatric Biktarvy now approved

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217.1.0.9 8️⃣ IRIS (Immune Reconstitution Inflammatory Syndrome)

217.1.0.9.1 Definition

• Paradoxical worsening of pre-existing infection or new presentation of subclinical infection after starting ART
• Due to immune recovery

217.1.0.9.2 Risk Factors

• Low CD4 baseline (< 100)
• High HIV viral load
• Rapid CD4 increase
• Specific OIs (TB, cryptococcal meningitis, KS, MAC, PML)

217.1.0.9.3 Common IRIS Triggers

• TB IRIS: ~ 20% of TB-HIV starting ART; paradoxical worsening (LAP, cavitary lung)
• Cryptococcal IRIS: 20-40%; new meningitis or worsening
• KS IRIS: KS flare
• MAC IRIS: localized lymphadenitis
• PML IRIS: paradoxical worsening in JC virus PML

217.1.0.9.4 Management

• Continue ART
• Treat underlying OI
• Steroid for severe (especially CNS IRIS, TB IRIS)
• ICU support if needed

217.1.0.9.5 Prevention

• Treat OI first if possible (CD4 < 50 + severe OI)
• Delay ART 2-4 wk after OI treatment start in some scenarios
• Special: CNS TB IRIS → delay 4-8 wk
• Don’t delay if CD4 < 50 + non-CNS OI

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217.1.0.10 9️⃣ PrEP + PEP

217.1.0.10.1 PrEP (Pre-Exposure Prophylaxis)

217.1.0.10.1.1 Oral Daily

• Truvada (TDF/FTC) — first FDA approved 2012
• Descovy (TAF/FTC) — 2019; no renal/bone toxicity concerns

217.1.0.10.1.2 Long-Acting Injectable

• Cabotegravir LA (Apretude) — IM injection every 2 months
• FDA 2021
• 99%+ efficacy in HPTN 083 trial
• More acceptable for some patients (less daily reminder)

217.1.0.10.1.3 Lenacapavir LA

• SC injection every 6 months
• FDA expected for PrEP 2025-2026
• PURPOSE-1 + PURPOSE-2 trials 100% prevention in cisgender women + MSM
• Major breakthrough — twice yearly dosing

217.1.0.10.1.4 2-1-1 Dosing (Event-Based)

• Truvada 2 pills 2-24 hr before sex + 1 pill 24 hr after + 1 pill 48 hr after
• For MSM
• Less frequent dosing for occasional exposure

217.1.0.10.2 PrEP Indications (2024 CDC)

• Adults + adolescents at risk:
  • MSM with multiple partners
  • Transgender women
  • Sexually active HIV-negative individuals with HIV-positive partner
  • IDU
  • High-risk heterosexual women / men
  • Discordant partnerships
• 2024 CDC: routinely offer + discuss with all sexually active patients

217.1.0.10.3 Monitoring on PrEP

• HIV test q3 mo (rule out breakthrough infection)
• Renal function (TDF)
• STDs q3-6 mo
• Adherence counseling

217.1.0.10.4 PEP (Post-Exposure Prophylaxis)

• Within 72 hours of exposure
• 3-drug ART × 28 days
• TDF/FTC + raltegravir or dolutegravir (preferred)
• Source patient testing if accessible
• HIV testing baseline + 4-6 wk + 3 mo
• HBV / HCV / syphilis / STDs concurrent

217.1.0.10.5 Doxy-PEP

• Doxycycline 200 mg PO within 72 hr of unprotected sex
• For MSM + transgender women + > 1 STI in past year
• Reduces chlamydia + gonorrhea + syphilis
• Adjunct to HIV PrEP

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217.1.0.11 10. Long-Term Considerations + Aging

217.1.0.11.1 ART-Associated Complications

• Cardiovascular (statin + lifestyle)
• Renal (TDF history)
• Bone (DEXA)
• Lipid abnormalities
• Insulin resistance + diabetes
• Neurocognitive (HAND — HIV-Associated Neurocognitive Disorders)

217.1.0.11.2 Cancer Screening

• HPV (anal Pap MSM, cervical Pap in women)
• Lung CA (smokers)
• Hepatocellular CA (HBV/HCV)
• Skin (sun-exposed)
• Colorectal
• Breast, prostate per general

217.1.0.11.3 Vaccinations

• Annual flu
• COVID-19 boosters
• Hepatitis A + B (if not immune)
• Pneumococcal (PCV20 or PCV21)
• HPV
• Shingrix (if CD4 ≥ 200)
• MMR (if CD4 ≥ 200 + non-immune)

217.1.0.11.4 Mental Health + Substance Use

• Depression, anxiety screening
• Substance use treatment integration
• Harm reduction

217.1.0.11.5 Adherence Support

• 95%+ adherence ideal for full suppression
• Pill burden minimization (single tablet)
• Long-acting injectable for some
• Reminder systems, peer support

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