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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This 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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