How to approach an HIV patient in the ward, emergency, and OPD. What to do next after screening is positive, how to stage it on the basis of different history, examinations, and clinical investigations. What are the different treatment options based on the risk factors and co-morbidities of the patient and on the basis of the stage of the patient? What treatment should be given prophylactically to treat it effectively?
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Comprehensive Clinical Approach to HIV: Diagnosis, Staging, Treatment, and Prophylaxis
PART 1: APPROACHING THE HIV PATIENT BY SETTING
A. Outpatient Department (OPD) Approach
Who to screen (opt-out universal screening):
- All adults and adolescents aged 13-64 years (CDC recommendation)
- All pregnant women
- Anyone seeking STI treatment
- All patients requiring TB treatment
- Annual screening for high-risk individuals (MSM, sex workers, IV drug users, partners of known HIV-positive persons)
History to take in OPD:
- Risk factors: sexual history (number of partners, condom use, anal intercourse), IV drug use, blood transfusions, occupational exposures, tattooing
- Symptoms of acute HIV syndrome: fever, pharyngitis, lymphadenopathy, rash, headache, myalgia
- Symptoms of immune suppression: recurrent oral candidiasis, chronic diarrhea, weight loss >10%, recurrent chest infections, night sweats
- Prior HIV test results
- Travel history (TB-endemic areas)
- Psychiatric and substance use history
Physical exam in OPD:
- BMI and weight
- Lymphadenopathy (persistent generalized lymphadenopathy = WHO Stage 1)
- Oral cavity: thrush, hairy leukoplakia, aphthous ulcers, angular cheilitis
- Skin: pruritic papular eruptions, seborrheic dermatitis, herpes zoster, warts, molluscum contagiosum, Kaposi sarcoma lesions
- Chest: signs of pulmonary TB or PCP
- Abdomen: hepatosplenomegaly
- Neurological: cognitive function, peripheral neuropathy
- Genital/anal: STIs, anal condylomata
B. Emergency Department (ED) Approach
As noted in Rosen's Emergency Medicine, ED screening plays a key role in detecting HIV in underserved, hard-to-reach populations. The modern ED physician may encounter HIV patients for:
- Acute HIV syndrome (seroconversion illness)
- HIV-associated opportunistic infections
- ART side effects
- PrEP/PEP initiation
- Linkage to care for newly diagnosed patients
ED HIV Testing:
- Opt-out testing at triage is standard practice in many EDs
- Rapid point-of-care tests: INSTI® (fingerprick) or OraQuick® (oral swab) - these are antibody-based
- 4th-generation Ag/Ab combination tests: window period ~4 weeks (more sensitive)
- If initial rapid test negative but high-risk exposure within 4 weeks: retest at 3 months; advise condoms in the interim
Acute HIV Syndrome in the ED (Classic Presentation):
From Harrison's Principles of Internal Medicine:
| General | Neurologic | Dermatologic |
|---|---|---|
| Fever | Meningitis | Erythematous maculopapular rash |
| Pharyngitis | Encephalitis | Mucocutaneous ulceration |
| Lymphadenopathy | Peripheral neuropathy | |
| Headache/retroorbital pain | Myelopathy | |
| Arthralgias/myalgias | ||
| Lethargy/malaise | ||
| Nausea/vomiting/diarrhea |
Think of acute HIV syndrome in anyone presenting with a mononucleosis-like illness with skin rash - especially with a relevant history.
ED Management Priorities:
- Manage presenting opportunistic infection (seek Infectious Diseases consultation)
- Assess ART side effects: NRTIs cause pancreatitis/hepatitis (mitochondrial toxicity); PIs cause GI side effects; Nevirapine can cause hepatic necrosis; Atazanavir causes Gilbert-like syndrome; Efavirenz causes neuropsychiatric effects
- Post-exposure prophylaxis (PEP) if within 72 hours of exposure
C. Ward (Inpatient) Approach
When an HIV patient is admitted:
- Stabilize the immediate presenting problem (PCP, cryptococcal meningitis, TB, etc.)
- Full systems review - HIV affects every organ system
- CD4 count and viral load - guides management decisions
- ART status: if not on ART, plan to start; if on ART, check adherence and virologic control
- Screening for comorbidities: cardiovascular risk, diabetes, renal function (TDF nephrotoxicity), liver disease (HBV/HCV co-infection), mental health, lipid profile
- Isolation: standard precautions + respiratory precautions if TB suspected
- Nutritional assessment
PART 2: AFTER SCREENING IS POSITIVE - WHAT TO DO NEXT
Step 1: Confirmatory Testing
HIV diagnosis is a two-step process (from Rosen's Emergency Medicine):
- Screening test (ELISA/4th-generation Ag/Ab combo test) - positive
- Confirmatory test (Western blot or HIV-1/HIV-2 differentiation immunoassay)
Step 2: Baseline Workup After Confirmed Diagnosis
Mandatory investigations:
- CD4+ T cell count (absolute count + percentage)
- HIV viral load (HIV-1 RNA PCR, copies/mL)
- HIV drug resistance testing (genotype) - before starting ART
- Complete blood count
- Liver function tests (LFTs), renal function (creatinine, eGFR, urinalysis)
- Fasting lipid profile + blood glucose
- HBsAg, HBsAb, HBcAb (HBV co-infection - affects ART choice)
- Anti-HCV antibody (HCV co-infection)
- VDRL/RPR (syphilis)
- Toxoplasma IgG
- CMV IgG
- Chest X-ray
- Mantoux/TST or IGRA for latent TB
- Pap smear (women)
- STI panel (gonorrhea, chlamydia)
- Vaccination history review
From Harrison's: CD4 counts should be measured at time of diagnosis and every 3-6 months for the first 2 years. HIV RNA levels (viral load) are the best indicator of treatment efficacy.
Step 3: Counseling
- Disclosure counseling
- Risk reduction counseling (condom use, needle exchange)
- Partner notification
- Pre-treatment adherence counseling
- Psychosocial support
PART 3: STAGING HIV DISEASE
WHO Clinical Staging System
From Dermatology (5th Ed.) and corroborated by multiple sources:
| Stage | Description | CD4 Correlate | Key Conditions |
|---|---|---|---|
| Stage 1 | Asymptomatic | ≥500 cells/mm³ | Asymptomatic; persistent generalized lymphadenopathy (PGL) |
| Stage 2 | Mild | 350-499 cells/mm³ | Herpes zoster; fungal nail infection; pruritic papular eruptions; angular cheilitis; recurrent oral ulcers; seborrheic dermatitis; moderate unexplained weight loss (<10% body weight); recurrent upper respiratory infections |
| Stage 3 | Advanced | 200-349 cells/mm³ | Persistent oral candidiasis; oral hairy leukoplakia; severe unexplained weight loss (>10%); pulmonary TB; severe bacterial infections (pneumonia, meningitis); unexplained anemia (<8 g/dL); unexplained thrombocytopenia (<50×10⁹/L); unexplained chronic diarrhea >1 month; unexplained persistent fever >1 month |
| Stage 4 | Severe (AIDS) | <200 cells/mm³ | PCP; CMV retinitis/other; cerebral toxoplasmosis; cryptococcal meningitis; HIV wasting syndrome; HIV encephalopathy/dementia; Kaposi sarcoma; extrapulmonary TB; non-typhoidal Salmonella septicemia; progressive multifocal leukoencephalopathy (PML); candidal esophagitis; disseminated MAC |
CDC Classification (also used clinically)
- Category A: CD4 ≥500; asymptomatic or PGL or acute HIV
- Category B: CD4 200-499; symptomatic but not AIDS-defining (e.g., oral candidiasis, recurrent VZV, cervical dysplasia, ITP)
- Category C (AIDS): CD4 <200 OR presence of any AIDS-defining illness
CD4 Count and Risk of Specific OIs (from Harrison's)
| CD4 count | Opportunistic infections at risk |
|---|---|
| <500/μL | TB, bacterial pneumonia, herpes zoster, Kaposi sarcoma |
| <200/μL | PCP, mucocutaneous candidiasis |
| <100/μL | CMV retinitis, cerebral toxoplasmosis, cryptococcal meningitis, MAC |
| <50/μL | Disseminated MAC, CMV disease, CNS lymphoma, PML |
Key Staging History Features
History pointing to staging:
- Weight loss: mild (<10%) = Stage 2; severe (>10%) = Stage 3-4; wasting = Stage 4
- Duration and severity of diarrhea
- Cough duration and character (productive TB vs. dry PCP cough)
- Night sweats, recurrent fevers
- Neurological symptoms (headache, visual changes, confusion, seizures)
- Skin lesions (their nature and distribution)
- Prior opportunistic infections
Examination clues:
- Oral thrush (Stage 3) vs. esophageal candidiasis (Stage 4)
- Hairy leukoplakia (Stage 3) - white corrugated plaques on lateral tongue
- KS lesions - violaceous skin/mucosal plaques (Stage 4)
- Hepatosplenomegaly
- Retinal examination (CMV retinitis - cotton wool spots, hemorrhages)
- Fundoscopy for CMV retinitis in CD4 <100
- Focal neurological signs (toxoplasmosis, PML, HIV dementia)
PART 4: ANTIRETROVIRAL THERAPY (ART)
When to Start ART
Universal and immediate - ART is indicated for ALL HIV-positive patients regardless of CD4 count, including:
- Asymptomatic patients with high CD4 counts
- Pregnant women (even if CD4 >500)
- Patients with TB (start ART within 2-8 weeks of TB treatment initiation, unless CD4 <50 - start within 2 weeks)
- Patients with other AIDS-defining illnesses
- For prevention of transmission ("Treatment as Prevention" = TasP)
Exception: delay ART in cryptococcal meningitis until CSF is sterilized (typically 4-6 weeks) to prevent IRIS.
Drug Classes Available (Goldman-Cecil)
Over 30 FDA-approved antiretrovirals targeting different steps of the HIV lifecycle:
| Class | Mechanism | Examples |
|---|---|---|
| NRTIs (Nucleoside Reverse Transcriptase Inhibitors) | Inhibit reverse transcriptase (chain terminators) | Tenofovir (TDF/TAF), Emtricitabine (FTC), Lamivudine (3TC), Abacavir (ABC), Zidovudine (ZDV) |
| NNRTIs (Non-Nucleoside RTIs) | Allosteric inhibition of reverse transcriptase | Efavirenz (EFV), Rilpivirine (RPV), Doravirine (DOR), Nevirapine (NVP) |
| PIs (Protease Inhibitors) | Block HIV protease | Darunavir (DRV), Atazanavir (ATV), Lopinavir/r (LPV/r) |
| INSTIs (Integrase Strand Transfer Inhibitors) | Block integration of viral DNA | Dolutegravir (DTG), Bictegravir (BIC), Raltegravir (RAL), Elvitegravir (EVG) |
| Entry inhibitors | Block viral entry | Maraviroc (CCR5 antagonist), Enfuvirtide (fusion inhibitor) |
| Attachment inhibitors | Block gp120-CD4 binding | Fostemsavir |
Preferred First-Line Regimens (Standard of Care)
Standard regimen = 2 NRTIs + 1 INSTI (backbone)
Preferred regimens (once-daily single tablets):
| Regimen | Trade Name | Class Combination |
|---|---|---|
| TAF/FTC/BIC | Biktarvy | 2 NRTI + INSTI - preferred (high barrier, no food restrictions) |
| ABC/3TC/DTG | Triumeq | 2 NRTI + INSTI (requires HLA-B*5701 testing before ABC) |
| TDF/FTC + DTG | Separate pills (or Delstrigo analog) | 2 NRTI + INSTI |
| TAF/FTC/RPV | Odefsey | 2 NRTI + NNRTI (only if VL <100,000 and CD4 >200) |
| TDF/3TC/DOR | Delstrigo | 2 NRTI + NNRTI |
DTG (dolutegravir) is the most widely used anchor agent globally due to high barrier to resistance, good tolerability, and cost.
ART Choice Based on Comorbidities and Risk Factors
| Comorbidity / Risk Factor | Preferred ART Strategy |
|---|---|
| Renal disease (CKD/eGFR <50) | Use TAF instead of TDF (less nephrotoxic); avoid tenofovir altogether if severe; use ABC/3TC/DTG |
| Hepatitis B co-infection | MUST include TDF (or TAF) + FTC/3TC (active against HBV); stopping these can cause HBV flare |
| Hepatitis C co-infection | Start ART first; check drug-drug interactions with DAAs; avoid drugs metabolized by same CYP3A4 enzymes |
| TB co-infection | TDF + 3TC + DTG preferred (EFV 600mg or DTG 50mg BID alternatives); avoid PIs with rifampicin |
| Pregnancy | TDF/FTC + DTG (preferred); DTG was historically avoided in periconception but now considered acceptable; avoid EFV in 1st trimester |
| Cardiovascular risk (high) | Avoid lopinavir/r, older PIs (dyslipidemia); prefer INSTI-based regimen + TAF/FTC |
| CNS disease / Neuropsychiatric | Avoid efavirenz (causes vivid dreams, suicidality, CNS effects up to 50%); prefer DTG or BIC |
| Anemia | Avoid zidovudine (causes anemia, neutropenia) |
| Diabetes/metabolic syndrome | Avoid lopinavir/r; prefer INSTI-based regimens |
| Suspected NNRTI resistance | Use INSTI-based regimen (DTG has high genetic barrier) |
| Drug-drug interactions (polypharmacy) | INSTIs generally have fewer interactions; check PI interactions with cardiac drugs, statins, anticoagulants |
Key Drug-Drug Interactions to Avoid (Goldman-Cecil Table 357-4)
- All PIs: do NOT combine with lovastatin/simvastatin (risk myopathy); sildenafil (severe hypotension); salmeterol; direct oral anticoagulants (apixaban, rivaroxaban, ticagrelor)
- Dolutegravir: do NOT combine with dofetilide
- Rifampicin (for TB): requires dose adjustment - DTG 50mg BID or use EFV 600mg; avoid with boosted PIs
- Efavirenz: CYP2B6 inducer - reduces levels of many co-administered drugs
Monitoring on ART
- HIV viral load at 4-8 weeks after starting, then every 3-6 months
- Goal: viral load <50 copies/mL (undetectable) by 6 months
- CD4 count every 3-6 months (first 2 years), then annually
- Virologic failure = confirmed HIV RNA >200 copies/mL on treatment
- When failure occurs: assess adherence, check drug resistance genotype, redesign regimen with ≥2 active drugs
PART 5: PROPHYLAXIS AGAINST OPPORTUNISTIC INFECTIONS
Primary Prophylaxis (preventing first episode)
From Harrison's OI prevention guidelines (DHHS 2014):
| Pathogen | Indication | First Choice | Alternative |
|---|---|---|---|
| Pneumocystis jirovecii (PCP) | CD4 <200/μL OR CD4% <14 OR prior oral candidiasis | TMP-SMX DS 1 tablet daily (or SS daily) | Dapsone 100mg/day; Atovaquone 1500mg/day; Aerosolized pentamidine 300mg monthly |
| Toxoplasma gondii | CD4 <100/μL AND Toxoplasma IgG positive | TMP-SMX DS 1 tablet daily | Dapsone 50mg/day + pyrimethamine 50mg/week + leucovorin 25mg/week |
| Mycobacterium avium complex (MAC) | CD4 <50/μL (unless starting ART immediately) | Azithromycin 1200mg weekly OR clarithromycin 500mg BID | Rifabutin 300mg/day |
| Latent TB (LTBI) | TST ≥5mm OR IGRA positive OR recent exposure | Isoniazid 300mg/day + pyridoxine 25mg/day for 9 months | Rifampicin 600mg/day × 4 months; 3HP (isoniazid + rifapentine weekly × 12 weeks) |
| Cryptococcus | CD4 <50 in high-prevalence areas | Fluconazole 200mg/day (some guidelines) | - |
| Varicella (VZV) | No prior immunity, recent exposure | VZV vaccine (if CD4 >200) | VZIg if exposure and immunocompromised |
Note on PCP prophylaxis: TMP-SMX also provides coverage against Toxoplasma - one drug, two birds. Stop prophylaxis once CD4 rises above threshold on ART and remains elevated for 3-6 months.
Secondary Prophylaxis (maintenance therapy after first episode)
| Pathogen | Maintenance Therapy |
|---|---|
| PCP | TMP-SMX DS once daily |
| Toxoplasma encephalitis | Sulfadiazine 500-1000mg QID + pyrimethamine 25-50mg/day + leucovorin 10-25mg/day |
| CMV retinitis | Valganciclovir 900mg daily (can discontinue when CD4 >100 for >6 months) |
| MAC | Clarithromycin 500mg BID + ethambutol 15mg/kg/day (± rifabutin) |
| Cryptococcal meningitis | Fluconazole 200mg daily |
| Herpes simplex (frequent) | Acyclovir 400mg BID or valacyclovir 500mg BID |
| Mucocutaneous Candida (recurrent) | Fluconazole 100-200mg daily |
Vaccines for HIV Patients (CD4 >200 preferred timing)
- Influenza (annually) - inactivated only
- Pneumococcal (PCV13 then PPSV23)
- HBV series (if seronegative)
- HAV (if seronegative)
- Tdap
- HPV (up to age 45)
- Live vaccines (MMR, VZV, yellow fever): only if CD4 >200
PART 6: PRE- AND POST-EXPOSURE PROPHYLAXIS
PrEP (Pre-Exposure Prophylaxis)
- Indication: HIV-negative individuals at substantial risk (MSM, serodiscordant couples, IV drug users, sex workers)
- Regimen: TDF 300mg/FTC 200mg (Truvada) once daily OR TAF/FTC (Descovy) once daily
- Before starting: Confirm HIV-negative (Ag/Ab test); screen for renal function, HBV, STIs
- Monitoring: HIV test and renal function every 3 months; STI screening every 6 months
PEP (Post-Exposure Prophylaxis)
From Washington Manual of Medical Therapeutics:
- Window: must be started within 72 hours of exposure (sooner = better)
- Duration: 28 days
- Regimen: TDF 300mg/FTC 200mg once daily + Dolutegravir 50mg once daily (or Raltegravir 400mg BID)
- Indications: Unprotected intercourse with known/likely HIV+ person, needle sharing, occupational needlestick from HIV+ source
- Follow-up: HIV test at baseline, 6 weeks, and 3 months; counsel on risk reduction
PART 7: SPECIAL SITUATIONS AND CO-MORBIDITY MANAGEMENT
HIV + Tuberculosis (most important co-infection globally)
- Start TB treatment first, add ART within 2 weeks if CD4 <50; within 8 weeks if CD4 >50
- Use DTG 50mg BID (or EFV 600mg) with rifampicin-based regimens
- Watch for IRIS (immune reconstitution inflammatory syndrome) - worsening of symptoms 2-8 weeks after ART initiation
- Treat LTBI with isoniazid + pyridoxine in ALL HIV patients regardless of TST if living in TB-endemic areas
HIV + Hepatitis B
- Must include TDF/TAF + 3TC or FTC in all ART regimens (dually active against HIV and HBV)
- Stopping these drugs causes HBV flare - never discontinue without careful planning
- Monitor HBV viral load, LFTs
HIV + Hepatitis C
- DAA (direct-acting antivirals) therapy has >95% cure rate for HCV
- Check drug interactions (ledipasvir/sofosbuvir with TAF)
- ART should be started concurrently or before HCV treatment
HIV + Cardiovascular Disease
- HIV itself is an independent cardiovascular risk factor (comparable to smoking)
- Screen with fasting lipids, glucose; Framingham risk calculation
- Prefer INSTIs over PIs; avoid simvastatin/lovastatin with PIs
- Aggressive management of traditional risk factors (smoking cessation, statin therapy, BP control)
HIV + CNS Disease
- HIV-associated dementia/neurocognitive impairment: ART with good CNS penetration (DTG, EFV, AZT have good CNS penetration)
- Cryptococcal meningitis: amphotericin B + flucytosine (induction) → fluconazole (consolidation/maintenance); delay ART 4-6 weeks
- Toxoplasma encephalitis: pyrimethamine + sulfadiazine + leucovorin; start ART promptly
- Progressive multifocal leukoencephalopathy (PML due to JC virus): no specific therapy; ART is the treatment - immune restoration suppresses JC virus replication
Pregnancy and HIV
- ART mandatory for all HIV+ pregnant women (TasP)
- Goal: undetectable viral load before delivery
- Preferred: TDF/FTC + DTG (dolutegravir now considered acceptable even in periconception)
- Elective C-section if viral load >1000 copies/mL at 36 weeks
- Infant prophylaxis: NVP or AZT for 4-6 weeks postpartum
- Breastfeeding: avoid if safe alternatives available (formula); if breastfeeding, continue maternal ART throughout
Summary Flow: HIV Patient Encounter
Screening (ELISA/4th-gen Ag/Ab)
↓ Positive
Confirmatory test (Western blot / differentiation assay)
↓ Confirmed
Baseline workup (CD4, VL, resistance, LFT, RFT, HBV/HCV, TB, STIs)
↓
WHO Staging (Stage 1-4) + CDC Classification (A/B/C)
↓
Start ART (universal) → Preferred: 2 NRTI + INSTI (TAF/FTC/BIC or ABC/3TC/DTG)
↓ Adjust for comorbidities
OI Prophylaxis based on CD4:
<200: TMP-SMX (PCP + Toxo)
<100: Check Toxo IgG; confirm TMP-SMX covers both
<50: Add Azithromycin (MAC); consider fluconazole
↓
Monitor: VL at 4-8 wks → goal <50 copies/mL by 6 months
CD4 every 3-6 months
Stop prophylaxis when CD4 recovers above threshold on ART
Sources:
- Harrison's Principles of Internal Medicine, 22nd Ed. (2025) - Chapter 208 (HIV Disease) and OI Prevention Guidelines
- Rosen's Emergency Medicine: Concepts and Clinical Practice - Chapter 121 (HIV Testing and ED Management)
- Goldman-Cecil Medicine - Chapter 357 (Antiretroviral Treatment of HIV)
- Dermatology: 5th Ed. - Chapter 78 (HIV and Mucocutaneous Disease, WHO Staging Table)
- Washington Manual of Medical Therapeutics - PEP/PrEP protocolsThis is a comprehensive, evidence-based answer drawn from Harrison's Principles of Internal Medicine (22nd Ed.), Rosen's Emergency Medicine, Goldman-Cecil Medicine, Dermatology (5th Ed.), and the Washington Manual of Medical Therapeutics. Here is a structured breakdown of the entire clinical approach:
Comprehensive Clinical Approach to HIV
PART 1: APPROACH BY CLINICAL SETTING
A. OPD (Outpatient) Approach
Who to screen (opt-out universal screening):
- All adults/adolescents aged 13-64 years
- All pregnant women
- Anyone seeking STI treatment
- All patients requiring TB treatment
- Annual repeat screening for high-risk individuals: MSM, sex workers, IV drug users, serodiscordant couples
History:
- Risk factors: sexual history (partners, condom use, receptive anal intercourse), IV drug use, blood transfusions, tattooing, occupational exposures
- Symptoms of acute HIV: fever, pharyngitis, lymphadenopathy, rash, arthralgia
- Symptoms of immune suppression: oral thrush, chronic diarrhea, weight loss >10%, night sweats, recurrent chest infections, neurological symptoms
- Prior HIV test results; psychiatric and substance use history
Physical Examination:
- BMI and weight
- Lymphadenopathy (persistent generalized = WHO Stage 1)
- Oral cavity: thrush, hairy leukoplakia, angular cheilitis, aphthous ulcers
- Skin: pruritic papular eruptions, seborrheic dermatitis, herpes zoster, molluscum contagiosum, Kaposi sarcoma (violaceous plaques)
- Chest: signs of PCP, pulmonary TB
- Abdomen: hepatosplenomegaly
- Neurology: peripheral neuropathy, cognitive function
- Eyes: CMV retinitis (cotton-wool spots, hemorrhages) if CD4 <100
- Anogenital: STIs, anal/cervical dysplasia
B. Emergency Department (ED) Approach
The ED is a key setting for detecting HIV in hard-to-reach populations. Modern ED physicians may also initiate PrEP, PEP, and ART.
ED HIV Testing:
- Opt-out testing at triage is standard
- Rapid POC tests: INSTI® (fingerprick) or OraQuick® (oral) - antibody-based
- 4th-generation Ag/Ab combination tests: window period ~4 weeks (preferred)
- If initial test negative but high-risk exposure <4 weeks: retest at 3 months; advise condoms
Acute HIV Syndrome (seroconversion illness) - think of it in mononucleosis-like presentations with rash:
| General | Neurologic | Dermatologic |
|---|---|---|
| Fever | Meningitis | Erythematous maculopapular rash |
| Pharyngitis | Encephalitis | Mucocutaneous ulceration |
| Lymphadenopathy | Peripheral neuropathy | |
| Headache/retroorbital pain | Myelopathy | |
| Arthralgias/myalgias, malaise | ||
| Nausea/vomiting/diarrhea |
ED Management Priorities:
- Manage the presenting OI (consult Infectious Diseases)
- Assess ART side effects: NRTIs → pancreatitis/hepatitis; nevirapine → hepatic necrosis; efavirenz → neuropsychiatric effects; atazanavir → jaundice (Gilbert-like); PIs → GI side effects
- Initiate PEP if within 72 hours of exposure
- Link patient to outpatient HIV care
C. Ward (Inpatient) Approach
- Stabilize the immediate presenting illness (PCP, cryptococcal meningitis, TB, etc.)
- Full systems review - HIV is a multisystem disease
- Obtain CD4 count and HIV viral load urgently
- Assess ART status: if not on ART, plan initiation; if on ART, check adherence and viral suppression
- Screen for comorbidities: cardiovascular disease, diabetes, CKD (TDF nephrotoxicity), HBV/HCV co-infection, mental health disorders
- Nutritional assessment
- Infection control: standard precautions + airborne precautions if TB is suspected
PART 2: AFTER SCREENING IS POSITIVE - NEXT STEPS
Step 1: Confirmation
HIV diagnosis is a two-step process:
- Screening: ELISA or 4th-generation Ag/Ab combo test
- Confirmation: Western blot OR HIV-1/2 differentiation immunoassay
Step 2: Baseline Investigations
| Investigation | Purpose |
|---|---|
| CD4+ T cell count (absolute + %) | Staging, prophylaxis thresholds |
| HIV-1 RNA (viral load, PCR) | Baseline viremia; treatment response monitoring |
| HIV genotype resistance test | Guide initial ART selection |
| CBC, LFT, RFT, urinalysis | Baseline organ function; monitor drug toxicity |
| Fasting lipid profile + glucose | Cardiovascular risk; ART baseline |
| HBsAg, HBsAb, HBcAb | HBV co-infection (affects ART choice critically) |
| Anti-HCV antibody | HCV co-infection |
| VDRL/RPR | Syphilis co-infection |
| Toxoplasma IgG | Risk assessment for toxo encephalitis |
| CMV IgG | Risk assessment |
| Chest X-ray | TB, PCP, lymphoma |
| Mantoux/TST or IGRA | Latent TB screening |
| Pap smear (women) | Cervical dysplasia (3x increased risk) |
| STI panel | Gonorrhea, chlamydia |
Step 3: Counseling
- Disclosure, risk reduction, partner notification
- Pre-treatment adherence counseling
- Psychosocial support and mental health referral
PART 3: STAGING HIV DISEASE
WHO Clinical Staging
| Stage | CD4 Correlate | Key Defining Conditions |
|---|---|---|
| Stage 1 - Asymptomatic | ≥500/mm³ | Asymptomatic; persistent generalized lymphadenopathy |
| Stage 2 - Mild | 350-499/mm³ | Herpes zoster, fungal nail infection, pruritic papular eruptions, angular cheilitis, recurrent oral ulcers, seborrheic dermatitis, moderate weight loss (<10%) |
| Stage 3 - Advanced | 200-349/mm³ | Oral candidiasis, oral hairy leukoplakia, pulmonary TB, severe bacterial infections (pneumonia, meningitis), severe weight loss (>10%), unexplained anemia <8g/dL, chronic diarrhea >1 month, unexplained persistent fever >1 month |
| Stage 4 - AIDS | <200/mm³ | PCP, CMV retinitis/disease, cerebral toxoplasmosis, cryptococcal meningitis, HIV wasting syndrome, HIV dementia/encephalopathy, Kaposi sarcoma, extrapulmonary TB, Candida esophagitis, disseminated MAC, PML |
CDC Classification
- Category A: CD4 ≥500; asymptomatic or PGL or acute HIV
- Category B: CD4 200-499; symptomatic but not AIDS-defining (oral candidiasis, cervical dysplasia, recurrent VZV, ITP)
- Category C (AIDS): CD4 <200 OR any AIDS-defining illness
CD4 Count and OI Risk Thresholds (Harrison's)
| CD4 Count | At-Risk Infections |
|---|---|
| <500/μL | TB, bacterial pneumonia, herpes zoster, early KS |
| <200/μL | PCP, mucocutaneous candidiasis |
| <100/μL | CMV disease, cerebral toxoplasmosis, cryptococcal meningitis |
| <50/μL | Disseminated MAC, CNS lymphoma, PML |
PART 4: ANTIRETROVIRAL THERAPY (ART)
When to Start
Universal and immediate for ALL HIV-positive patients regardless of CD4 count. Special timings:
- HIV + TB: start ART within 2 weeks if CD4 <50; within 8 weeks otherwise
- HIV + Cryptococcal meningitis: delay ART 4-6 weeks until CSF is sterilized (prevent fatal IRIS)
- Pregnant women: immediate ART (goal = undetectable VL before delivery)
Drug Classes
| Class | Mechanism | Key Agents |
|---|---|---|
| NRTIs | Chain-terminate reverse transcription | TDF, TAF, FTC, 3TC, ABC, AZT |
| NNRTIs | Allosteric RT inhibition | EFV, RPV, DOR, NVP |
| PIs | Block viral protease | DRV, ATV, LPV/r |
| INSTIs | Block viral DNA integration | DTG, BIC, RAL, EVG |
| Entry inhibitors | Block CCR5 or fusion | Maraviroc, enfuvirtide |
Preferred First-Line Regimens (2 NRTIs + 1 INSTI)
| Single-Tablet Regimen | Trade Name | Notes |
|---|---|---|
| TAF/FTC/BIC | Biktarvy | Preferred: high barrier, renal-sparing, no food restriction |
| ABC/3TC/DTG | Triumeq | Requires HLA-B*5701 testing (risk of ABC hypersensitivity) |
| TDF/FTC + DTG | Separate | Affordable; global standard (WHO preferred) |
| TAF/FTC/RPV | Odefsey | NNRTI-based; only if VL <100,000 and CD4 >200 |
| TDF/3TC/DOR | Delstrigo | NNRTI-based alternative |
ART Choice by Comorbidity
| Comorbidity | Preferred Approach |
|---|---|
| Renal disease / CKD | Use TAF (not TDF); severe CKD: ABC/3TC/DTG |
| Hepatitis B co-infection | MUST include TDF/TAF + FTC or 3TC (active against HBV; stopping causes flare) |
| Hepatitis C co-infection | Start ART; check DDIs with DAAs; >95% HCV cure rate with modern DAAs |
| TB co-infection | TDF/3TC + DTG 50mg BID with rifampicin; avoid boosted PIs |
| Pregnancy | TDF/FTC + DTG (now acceptable even periconception) |
| High cardiovascular risk | Avoid older PIs (dyslipidemia); prefer INSTI-based; check statin interactions |
| CNS disease / neuropsychiatric | Avoid efavirenz (up to 50% CNS side effects, suicidality); use DTG or BIC |
| Anemia | Avoid zidovudine (causes anemia + neutropenia) |
Key Drug Interactions to Avoid
- All PIs: do NOT co-administer lovastatin/simvastatin, sildenafil, salmeterol, direct oral anticoagulants (apixaban, rivaroxaban, ticagrelor)
- Rifampicin + boosted PIs: contraindicated (rifampicin drastically reduces PI levels)
- Dolutegravir + dofetilide: contraindicated (life-threatening arrhythmia risk)
- Efavirenz: CYP2B6 inducer - reduces levels of many co-medications
Virologic Monitoring and Failure
- Check viral load at 4-8 weeks after starting ART
- Target: <50 copies/mL by 6 months
- Virologic failure = confirmed HIV RNA >200 copies/mL on adherent therapy
- Action: assess adherence → drug resistance genotyping → redesign regimen with ≥2 active drugs (at least one with high barrier to resistance, e.g., DTG)
PART 5: OI PROPHYLAXIS
Primary Prophylaxis (Prevent First Episode)
| Pathogen | Trigger (CD4) | First Choice | Alternative |
|---|---|---|---|
| PCP (Pneumocystis jirovecii) | CD4 <200/μL or CD4% <14% | TMP-SMX DS 1 tab daily | Dapsone 100mg/day; atovaquone 1500mg/day; aerosolized pentamidine 300mg/month |
| Toxoplasma gondii | CD4 <100/μL + Toxo IgG positive | TMP-SMX DS daily (also covers PCP) | Dapsone 50mg/day + pyrimethamine 50mg/week + leucovorin |
| Mycobacterium avium complex (MAC) | CD4 <50/μL (unless ART starting immediately) | Azithromycin 1200mg weekly | Clarithromycin 500mg BID; rifabutin 300mg/day |
| Latent TB (LTBI) | TST ≥5mm or IGRA+ or endemic area exposure | Isoniazid 300mg/day × 9 months + pyridoxine 25mg/day | Rifampicin × 4 months; 3HP (weekly isoniazid/rifapentine × 12 weeks) |
| Fungal (cryptococcus) | CD4 <50 in high-prevalence areas | Fluconazole 200mg/day (some guidelines) | - |
Note: TMP-SMX DS covers both PCP and Toxoplasma - one drug covers two of the most important OIs.
Stop primary prophylaxis once CD4 rises above threshold on ART and remains there for 3-6 months.
Secondary Prophylaxis (Maintenance After Treatment)
| Pathogen | Maintenance Regimen |
|---|---|
| PCP | TMP-SMX DS once daily |
| Toxoplasma encephalitis | Sulfadiazine 500mg QID + pyrimethamine 25mg/day + leucovorin |
| Cryptococcal meningitis | Fluconazole 200mg daily (until CD4 >200 for >6 months) |
| CMV retinitis | Valganciclovir 900mg daily (can stop when CD4 >100 for >6 months on ART) |
| MAC | Clarithromycin 500mg BID + ethambutol 15mg/kg/day |
| Herpes simplex (recurrent/severe) | Acyclovir 400mg BID or valacyclovir 500mg BID |
| Mucocutaneous Candida (recurrent) | Fluconazole 100-200mg daily |
Vaccines in HIV (Preferably given when CD4 >200)
- Influenza (annual, inactivated only)
- Pneumococcal (PCV13 followed by PPSV23)
- HBV series (if seronegative)
- HAV (if seronegative)
- HPV (up to age 45)
- Tdap
- MMR and Varicella (live vaccines): only if CD4 >200
PART 6: PRE- AND POST-EXPOSURE PROPHYLAXIS
PrEP
- Who: HIV-negative persons at substantial ongoing risk (MSM, serodiscordant couples, IV drug users)
- Regimen: TDF/FTC (Truvada) or TAF/FTC (Descovy) once daily
- Pre-start: confirm HIV-negative; baseline renal function, HBV, STI screen
- Monitoring: HIV test + renal function every 3 months; STI every 6 months
PEP
- Window: must start within 72 hours (sooner = more effective)
- Duration: 28 days
- Preferred regimen: TDF/FTC once daily + Dolutegravir 50mg once daily (or raltegravir 400mg BID)
- Indications: unprotected intercourse with known/suspected HIV+ person; shared needle; occupational needlestick
- Follow-up: HIV test at baseline, 6 weeks, 3 months
Clinical Decision Flow
Screening (4th-gen Ag/Ab test)
↓ Positive
Confirmatory test (Western blot / differentiation assay)
↓ Confirmed
Baseline: CD4, VL, resistance genotype, LFT, RFT, HBV, HCV, TB, STIs
↓
WHO Stage 1-4 + CDC Category A/B/C
↓
Start ART universally → Preferred: TAF/FTC/BIC or TDF/3TC + DTG
Adjust for: TB, HBV, CKD, pregnancy, CNS disease, CVD
↓ Concurrent
OI Prophylaxis:
CD4 <200 → TMP-SMX (PCP + Toxoplasma)
CD4 <50 → + Azithromycin weekly (MAC)
LTBI+ → Isoniazid × 9 months
↓
Monitor VL at 4-8 weeks → Goal: <50 copies/mL by 6 months
CD4 every 3-6 months → Stop prophylaxis when CD4 rises above threshold
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