Immune System

HIV: screening, diagnosis, and counseling

Clinical Overview and When to Suspect HIV

— USPSTF Grade A: screen all adolescents and adults age 15–65 at least once; younger and older if at risk

— CDC: opt-out screening for everyone 13–64 in any healthcare encounter

— Pregnancy: screen at first prenatal visit and again in the third trimester in high-prevalence areas or with ongoing risk; rapid test in labor if status unknown

— MSM with new or multiple partners, transgender women

— PWID, sex workers, partners of HIV+ persons

— Diagnosis of another STI (syphilis, gonorrhea, chlamydia, hepatitis B/C), TB, or after sexual assault

— Patients starting PrEP (every 3 months) or PEP

— Mononucleosis-like illness in a sexually active adult (acute retroviral syndrome)

— Recurrent shingles, oral candidiasis, seborrheic dermatitis, unexplained lymphadenopathy, weight loss, thrombocytopenia, or new dementia

— Opportunistic infections: PCP, Kaposi sarcoma, cryptococcal meningitis, CMV retinitis, esophageal candidiasis

— Cervical dysplasia, anal dysplasia, or any AIDS-defining cancer

Board pearl: Step 3 commonly tests the opt-out framework — the correct answer is "inform the patient that HIV testing will be performed unless they decline," not "obtain separate written consent." Written consent is no longer required federally; some states still mandate documentation, but verbal opt-out satisfies USPSTF/CDC. Failure to offer screening at a primary care visit is the wrong answer.

Epidemiology snapshot (US): ~1.2 million people living with HIV; ~13% undiagnosed. New diagnoses concentrated in men who have sex with men (MSM), Black/Hispanic populations, the South, and people who inject drugs (PWID). Transmission risk per act is highest for receptive anal intercourse and shared injection equipment.

Universal screening recommendation:

Targeted/repeat screening (at least annually, sometimes q3–6 months):

Clinical scenarios that should trigger HIV testing regardless of stated risk:

Presentation Patterns and Key History

— Onset 2–4 weeks after exposure; lasts 1–3 weeks

— Fever (>96%), fatigue, pharyngitis, generalized lymphadenopathy, maculopapular rash on trunk/face/palms/soles, myalgia, headache, mucocutaneous ulcers, GI upset

— Often mistaken for mono, influenza, or secondary syphilis — the trunk rash + oral ulcers + recent unprotected sex is the classic Step 3 trigger

— Oral thrush, hairy leukoplakia (EBV, lateral tongue), recurrent vaginal candidiasis, zoster in young adult, ITP, seborrheic dermatitis, molluscum

— Constitutional: drenching sweats, >10% weight loss, chronic diarrhea

— Partners (number, gender, HIV status, geographic origin)

— Practices (vaginal/anal/oral; insertive vs receptive)

— Protection (condom use consistency, PrEP)

— Past STIs (syphilis, GC, HSV — all increase HIV acquisition)

— Pregnancy intentions and contraception

— Plus: injection drug use, needle sharing, transfusions before 1985 (developed countries), occupational exposures, tattoos abroad, commercial sex work, incarceration history

Step 3 management: A patient with fever, rash, and pharyngitis 3 weeks after a new sexual partner needs HIV RNA (viral load) ordered alongside the 4th-generation Ag/Ab test — antibody alone may still be negative in the window period (~10–14 days). Do not wait to "see if it resolves."

Acute (primary) HIV infection — "acute retroviral syndrome":

Clinical latency (chronic asymptomatic): median 8–10 years untreated; patients feel well but transmit. Persistent generalized lymphadenopathy may be the only finding.

Symptomatic/early AIDS (CD4 typically <500):

AIDS-defining (CD4 <200 or AIDS-defining illness): PCP, esophageal candidiasis, CMV retinitis, toxoplasma encephalitis, cryptococcal meningitis, MAC, Kaposi sarcoma, CNS lymphoma, PML, wasting

Targeted sexual & social history (the "5 P's plus"):

Physical Exam Findings (and Hemodynamic Assessment when relevant)

— Acute HIV: febrile, ill-appearing but hemodynamically stable; tachycardia from fever

— Advanced disease: cachexia, temporal wasting, BMI decline; orthostasis from adrenal insufficiency (CMV, MAC) or volume depletion from chronic diarrhea

— Sepsis physiology should prompt search for opportunistic infection or bacteremia (S. pneumoniae, Salmonella) — HIV+ patients have higher invasive pneumococcal disease risk

— Oral candidiasis (white plaques, scrape off) — strong predictor of CD4 <200–300

— Oral hairy leukoplakia (corrugated lateral tongue, does NOT scrape off, EBV-driven) — HIV until proven otherwise

— Kaposi sarcoma palatal lesions (violaceous)

— Aphthous ulcers, gingivitis

— Funduscopy: CMV retinitis = "pizza pie" hemorrhages + exudates when CD4 <50

— Seborrheic dermatitis (nasolabial folds, scalp), psoriasis flare, eosinophilic folliculitis

— Disseminated zoster, molluscum on face in adults

— Kaposi sarcoma plaques (HHV-8)

— Bacillary angiomatosis (Bartonella) — friable red papules

Board pearl: Oral thrush + unexplained weight loss in any adult = order HIV testing today, even without stated risk factors. This is a recurring vignette and the wrong answer is "empiric fluconazole and reassess."

General appearance & vitals:

HEENT:

Lymphatic: persistent generalized lymphadenopathy (≥2 extrainguinal sites, ≥1 cm, >3 months) — common in early chronic HIV; sudden bulky asymmetric nodes suggest lymphoma or TB

Skin:

Pulmonary: crackles or hypoxia with exertion → PCP; focal consolidation → bacterial pneumonia or TB

Abdominal: hepatosplenomegaly (MAC, lymphoma, hepatitis coinfection)

Neuro: focal deficits (toxoplasmosis, PML, CNS lymphoma), cognitive slowing (HIV-associated neurocognitive disorder), peripheral neuropathy

Anogenital: HSV ulcers, condylomata, anal dysplasia — perform digital anorectal exam in MSM

Diagnostic Workup — Initial Labs

— Detects p24 antigen + IgG/IgM antibodies

— Window period shortened to ~14–18 days post-exposure

— Sensitivity and specificity >99% in chronic infection

— Replaces older "ELISA then Western blot" algorithm (Western blot no longer recommended — missed acute infection)

— Step 1: 4th-gen Ag/Ab combo assay

— Step 2 (if reactive): HIV-1/HIV-2 antibody differentiation immunoassay (e.g., Geenius) — distinguishes HIV-1 vs HIV-2 and confirms

— Step 3 (if differentiation indeterminate or negative but initial reactive): HIV-1 RNA (viral load) by NAAT — this catches acute HIV where Ag/Ab positive but antibodies not yet developed

— Suspected acute retroviral syndrome (symptoms + recent exposure)

— Neonates born to HIV+ mothers (maternal antibodies cross placenta → antibody tests unreliable until 18 months; use HIV DNA/RNA PCR at 14–21 days, 1–2 months, 4–6 months)

— Post-exposure follow-up at very early intervals

— Fingerstick or oral fluid; 3rd-gen (antibody only) — longer window (~3 weeks)

— Use in L&D, ED, outreach; any reactive rapid test requires lab confirmation before disclosure as "positive"

— CD4 count and %, HIV-1 RNA quantitative viral load

— HIV genotype resistance testing (transmitted resistance ~10%)

— HLA-B*5701 if considering abacavir

— CBC, CMP, lipids, A1c, UA, hepatitis A/B/C serologies, syphilis (RPR), GC/CT (3-site in MSM), trichomonas, TB screen (IGRA), toxoplasma IgG, CMV IgG, varicella, G6PD, pregnancy test

— HPV screening (cervical cytology; anal cytology in MSM per local protocol)

Step 3 management: A reactive rapid test in clinic is preliminary positive — counsel as "likely positive, confirmation pending," do not start ART or notify partners until confirmatory testing returns.

Preferred initial test: 4th-generation HIV-1/2 antigen/antibody combination immunoassay

CDC/APHL diagnostic algorithm (memorize this for Step 3):

When to go straight to HIV RNA (NAAT):

Point-of-care/rapid tests:

Baseline labs once HIV confirmed:

Diagnostic Workup — Advanced or Confirmatory Studies

— Confirms acute HIV when Ag/Ab+ but antibody differentiation negative/indeterminate

— Quantifies viremia for staging and treatment monitoring

— A very low positive (<5,000 copies/mL) without confirmatory antibody raises suspicion for false positive — repeat; true acute HIV usually has VL >100,000

— Endemic in West Africa; slower progression, lower viral loads

— Naturally resistant to NNRTIs and enfuvirtide — regimen choice differs

— Suspect when antibody differentiation shows HIV-2 reactivity or in West African origin patient with low/undetectable HIV-1 RNA but immunologic decline

— Genotype at entry to care and at virologic failure

— Phenotype reserved for complex multi-class failure

— Integrase resistance must be specifically requested (not on standard genotype)

— Tropism assay (CCR5 vs CXCR4) only if considering maraviroc

— CD4 <200 → start PCP prophylaxis (TMP-SMX); check toxoplasma IgG

— CD4 <150 + endemic area → screen for histoplasmosis

— CD4 <100 + toxoplasma IgG+ → toxo prophylaxis (TMP-SMX usually covers)

— CD4 <50 → ophthalmology referral for dilated exam (CMV); consider MAC risk (no longer routine prophylaxis if ART started promptly)

Key distinction: A positive 4th-gen Ag/Ab + negative antibody differentiation is the acute HIV pattern — next step is HIV-1 RNA, not repeat antibody in 6 weeks. Missing this is a classic Step 3 distractor.

HIV-1 RNA quantitative viral load (NAAT):

HIV-2 considerations:

Resistance testing:

Staging and OI screening once diagnosed:

TB evaluation: IGRA preferred over TST in HIV (less affected by anergy); if positive and no active disease → treat latent TB (rifapentine-isoniazid 3HP or 9 months INH, considering ART interactions)

Imaging/specialty workup driven by symptoms: CXR for cough, head CT/MRI for focal neuro signs, LP with cryptococcal antigen and India ink if meningeal signs

Risk Stratification or First-Line Management Logic

— (1) Treat the patient — start ART rapidly (ideally same day or within 7 days), regardless of CD4

— (2) Prevent transmission — partner services, U=U counseling, condom/PrEP for partners

— (3) Prevent opportunistic infections — vaccines, prophylaxis based on CD4

— Multiple trials (RAPID, START) show survival benefit and improved retention

— Acceptable to start before genotype returns using a high-barrier regimen (e.g., bictegravir/TAF/FTC or dolutegravir + TAF/FTC)

— Avoid abacavir until HLA-B*5701 known; avoid efavirenz empirically due to resistance prevalence

— Defer ART briefly only for cryptococcal meningitis (wait 4–6 weeks — IRIS risk) and consider timing in TB meningitis

— Housing instability, mental illness, substance use, lack of insurance → link to Ryan White program, case management, peer navigation

— Same-day labs + first ART prescription + 2-week follow-up improves retention

— Inactivated annually: influenza

— Pneumococcal: PCV15 then PPSV23 at 8 weeks (or PCV20 alone)

— HepB (if non-immune), HepA, HPV through age 26 (consider through 45 shared decision), Tdap/Td, mpox (Jynneos) for at-risk

— Live vaccines (MMR, varicella, zoster live) only if CD4 ≥200; zoster recombinant (Shingrix) is preferred and safe at any CD4 for age ≥19

— Avoid live yellow fever, LAIV when CD4 <200

CCS pearl: On a CCS case of newly diagnosed HIV, order in sequence: CD4, HIV RNA, genotype, HLA-B*5701, hepatitis panel, STI panel, TB screen, pregnancy test → then bictegravir/TAF/FTC → schedule 2-week follow-up and partner notification counseling.

Three parallel decision streams after diagnosis:

Rapid ART initiation ("Rapid Start"):

Engagement/retention risk stratification:

Vaccinations at entry (give while CD4 measured):

U=U messaging: durably suppressed viral load (<200 copies/mL for ≥6 months) → no sexual transmission. Powerful adherence motivator and stigma reducer.

Pharmacotherapy — First-Line Drug Regimen

— Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) — Biktarvy; one pill daily; few interactions

— Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) — Triumeq; requires HLA-B*5701 negative; avoid if high CV risk

— Dolutegravir + (TAF or TDF)/FTC — flexible 2-pill option

— Dolutegravir/lamivudine (DTG/3TC) — 2-drug regimen; avoid if HBV co-infected, baseline VL >500,000, or genotype unavailable

— Weight gain (especially with TAF + INSTI combos); discuss diet/exercise

— Polyvalent cations (calcium, magnesium, iron, antacids) chelate INSTIs — separate dosing

— Dolutegravir + metformin → increase metformin levels; monitor

— Neuropsychiatric effects (insomnia, depression) — uncommon but real

— TDF: nephrotoxicity, ↓BMD; avoid if CrCl <60 or osteoporosis

— TAF: better renal/bone profile; modest lipid/weight increase

— Abacavir: HLA-B*5701 hypersensitivity (fatal); possible MI risk signal

— TDF or TAF + FTC/3TC also treats HBV — never stop abruptly in coinfection (flare risk)

— Rifampin (use rifabutin or boost dose), PPIs with rilpivirine, statins with PIs (avoid simvastatin/lovastatin), hormonal contraception with some PIs/EFV, methadone, anticonvulsants, St. John's wort

Board pearl: A patient with HIV/HBV coinfection must receive an ART regimen that includes TDF or TAF + (FTC or 3TC) — stopping these later causes severe hepatitis flare. Choosing DTG/3TC alone here is wrong.

Preferred initial regimens (DHHS 2024): integrase strand transfer inhibitor (INSTI)–based, given as single-tablet regimens

Key INSTI counseling points:

NRTI backbone considerations:

Long-acting injectable option: cabotegravir + rilpivirine IM every 1–2 months — for virologically suppressed patients with adherence challenges; requires baseline susceptibility and no chronic HBV

Avoid as initial therapy: efavirenz (resistance, neuropsych), older PIs as first-line, monotherapy of any kind

Drug interactions to scan every visit:

Procedures and Prevention Pharmacology (PrEP, PEP, Perinatal)

— Daily oral TDF/FTC (Truvada) — approved all routes of exposure, including PWID and cisgender women

— Daily oral TAF/FTC (Descovy) — not approved for receptive vaginal sex (no efficacy data)

— Cabotegravir IM every 2 months — superior to oral in trials, useful for adherence barriers

— On-demand "2-1-1" TDF/FTC for MSM only (off-label in US)

— Confirm HIV-negative with Ag/Ab + RNA (rule out acute HIV — starting PrEP during acute HIV breeds resistance)

— Renal function (CrCl ≥60 for TDF, ≥30 for TAF), HBV status, STI panel, pregnancy

— Counsel adherence; 7 daily doses for rectal protection, ~20 days for vaginal tissue protection

— Start within 72 hours (sooner is better); duration 28 days

— Preferred: TDF/FTC + dolutegravir (or raltegravir, or bictegravir)

— Indications: occupational needlestick from known/suspected HIV+ source, sexual assault, condom failure with high-risk partner, shared injection

— Baseline HIV test, repeat at 4–6 weeks and 3 months (4 months if 4th-gen test); after completion, transition high-ongoing-risk patients to PrEP

— All pregnant patients with HIV on ART; goal undetectable VL by delivery

— VL <1,000 at delivery → vaginal delivery acceptable; VL >1,000 or unknown → scheduled C-section at 38 weeks + IV zidovudine intrapartum

— Avoid artificial rupture of membranes, fetal scalp electrodes

— Neonate: ART prophylaxis (zidovudine alone if low risk; combination if higher risk); avoid breastfeeding in US (formula safe and available)

Step 3 management: Healthcare worker with hollow-bore needlestick from HIV+ source → draw baseline HIV, start 3-drug PEP immediately (don't wait for source labs), report to occupational health, repeat HIV at 6 weeks and 4 months.

PrEP (pre-exposure prophylaxis) — preventive medication for HIV-negative at-risk persons:

PrEP workup before starting and q3 months:

PEP (post-exposure prophylaxis):

Perinatal transmission prevention:

Special Populations — Elderly and Renal/Hepatic Impairment

— Fastest-growing HIV demographic in US; >50% of PLWH now ≥50

— Faster immune senescence, accelerated CVD, CKD, osteoporosis, frailty, neurocognitive decline, non-AIDS cancers

— Comprehensive geriatric assessment, polypharmacy review (HIV meds + cardiac/diabetic regimens = interaction minefield)

— Statin therapy: REPRIEVE trial → pitavastatin reduces MACE in PLWH ages 40–75 with low-moderate ASCVD risk; many experts now recommend statin for all PLWH ≥40

— Bone density screening at 50 (men) or at menopause (women); earlier if on TDF

— Continue cancer screening per general guidelines plus anal cytology in MSM and trans women

— TDF: avoid if CrCl <60; causes proximal tubulopathy (Fanconi-like), declining eGFR, ↓phosphate, glucosuria

— TAF: safe down to CrCl 30; preferred in CKD or osteoporosis

— BIC/TAF/FTC can be used with CrCl ≥30; for dialysis patients use specific approved formulations

— Dolutegravir blocks tubular creatinine secretion → benign ~0.1–0.2 mg/dL creatinine bump in first weeks; not true renal injury

— Cobicistat similarly raises creatinine

— Avoid nephrotoxin stacking (NSAIDs, aminoglycosides, IV contrast bursts) when on TDF

— Hepatitis B/C coinfection common; treat HCV with DAAs (check ART interactions — sofosbuvir/velpatasvir generally compatible)

— In cirrhosis: avoid nevirapine, dose-adjust some PIs; INSTIs generally safe

— Monitor LFTs at initiation and periodically; INSTI-related hepatotoxicity rare

Board pearl: A rise in creatinine from 1.0 to 1.2 after starting dolutegravir with stable UA and no proteinuria = expected creatinine-secretion blockade, continue therapy. Stopping ART here is the wrong answer.

Older adults (≥50) with HIV:

Screening cutoff caveat: USPSTF lists 15–65, but screen any older adult with risk factors or clinical suspicion — age alone is not protective. Many late diagnoses occur in older adults missed by clinicians.

Renal impairment:

Hepatic impairment:

Special Populations — Pregnancy, Pediatrics, and Other Subgroups

— Dolutegravir + (TAF or TDF)/FTC — now preferred throughout pregnancy including conception (early neural-tube signal not confirmed in larger data); shared decision-making for those trying to conceive

— Alternatives: raltegravir + TDF/FTC, darunavir/ritonavir + TDF/FTC

— Avoid efavirenz at conception (older concern), cobicistat-boosted regimens (declining levels in 2nd/3rd trimester), and stavudine/didanosine combinations

— VL every 1–2 months until suppressed, then monthly through 34–36 weeks, then at 36 weeks for delivery planning

— Continue ART through labor; IV zidovudine intrapartum if VL >1,000 or unknown

— Combined screening for HBV, HCV, syphilis, GC/CT each trimester

— HIV DNA/RNA PCR at 14–21 days, 1–2 months, 4–6 months; definitive negative requires 2 negative NAATs (one ≥1 month, one ≥4 months) plus negative antibody at 18–24 months

— Neonatal ART prophylaxis: zidovudine 4–6 weeks (low-risk) or combination (high-risk maternal VL)

— Start PCP prophylaxis at 4–6 weeks until HIV definitively excluded

— Avoid breastfeeding in US (formula safe); harm-reduction discussion if patient insists

— Confidentiality protections vary by state — most allow minors to consent to STI/HIV testing and treatment without parental notification

— Transitions of care from pediatric to adult clinic carry retention risk; warm handoff

Step 3 management: HIV+ pregnant woman at 36 weeks with VL 5,000 → schedule C-section at 38 weeks, give IV zidovudine ≥3 hours before delivery, neonate gets combination prophylaxis.

Pregnancy — preferred ART:

Antepartum management:

Infant management:

Adolescents:

Survivors of sexual assault: offer PEP within 72 hours, emergency contraception, STI prophylaxis (ceftriaxone + doxycycline + metronidazole), HBV vaccination/HBIG if non-immune, and mental-health linkage; mandatory reporting depends on age and state

Transgender patients: gender-affirming hormones do not significantly interact with INSTIs; counsel that hormones do not protect against HIV

Complications and Adverse Outcomes

— <500: zoster, oral/vaginal candida, TB reactivation, bacterial pneumonia, Kaposi sarcoma

— <200: PCP (Pneumocystis jirovecii — dyspnea, dry cough, ↑LDH, ground-glass on CT), esophageal candida, cryptosporidiosis

— <100: toxoplasmosis (ring-enhancing brain lesions), cryptococcal meningitis (↑opening pressure, India ink, CrAg)

— <50: CMV retinitis, MAC (fever, weight loss, ↑alk phos, anemia), CNS lymphoma, PML (JC virus, non-enhancing white matter)

— Paradoxical worsening of a treated or subclinical OI 2–8 weeks after ART start

— Highest risk: low baseline CD4 + active OI (TB, cryptococcus, MAC)

— Cryptococcal meningitis: defer ART 4–6 weeks to reduce fatal CNS IRIS

— Management: treat underlying OI, continue ART when possible, steroids for severe IRIS

— Cardiovascular: ~1.5–2× MI risk; chronic inflammation, dyslipidemia, ART effects (abacavir signal); start statin per REPRIEVE

— Renal: HIV-associated nephropathy (collapsing FSGS, more common in Black patients), TDF tubulopathy

— Bone: osteoporosis, fracture risk (TDF, low vitamin D, hypogonadism)

— Hepatic: HBV/HCV coinfection, NAFLD

— Malignancies: non-Hodgkin lymphoma, Kaposi, cervical, anal, lung, HCC

— HIV-associated neurocognitive disorders (HAND)

— Depression, substance use, suicide — screen each visit (PHQ-9)

Key distinction: New focal neuro deficits + ring-enhancing lesions with CD4 <100 → toxoplasmosis (empiric pyrimethamine-sulfadiazine, expect response in 2 weeks); non-enhancing white-matter lesions → PML (no specific therapy, optimize ART).

Opportunistic infections by CD4 threshold:

Immune Reconstitution Inflammatory Syndrome (IRIS):

Non-AIDS complications (now dominant cause of mortality):

Drug toxicities: TDF nephro/bone, abacavir hypersensitivity, efavirenz neuropsych, dolutegravir weight gain/insomnia, PI dyslipidemia/insulin resistance

When to Escalate Care — ICU, Consult, or Inpatient Triage

— Hypoxia (SpO2 <92% on RA) suggesting PCP or bacterial pneumonia

— Suspected meningitis/encephalitis (fever, headache, AMS, focal deficit) — admit for LP, imaging, empiric therapy

— Disseminated OI with hemodynamic instability or inability to tolerate POs

— Severe IRIS, severe ART hypersensitivity (abacavir, nevirapine SJS)

— New AIDS-defining cancer requiring staging/treatment

— Pregnancy with complications

— Respiratory failure requiring HFNC/NIV/intubation (severe PCP — add steroids if PaO2 <70 or A-a gradient >35 on RA)

— Septic shock, status epilepticus, severe IRIS with airway compromise

— Cryptococcal meningitis with very high opening pressure requiring serial LPs

— Infectious Disease: any new HIV diagnosis ideally; mandatory for treatment failure, resistance, complex OI, pregnancy, pediatrics

— Hepatology/GI: HBV/HCV coinfection, cirrhosis evaluation

— Oncology: AIDS-defining and non-AIDS cancers

— Ophthalmology: CD4 <50 baseline exam; any visual change

— OB: prenatal HIV care coordinated with ID

— Psychiatry/SUD: untreated depression, opioid use disorder (link to MOUD)

— Social work/case management: housing, Ryan White, ADAP enrollment

— Discharge with ART filled in hand, not just prescribed

— Confirmed outpatient follow-up within 7–14 days

— Bridging from inpatient to Ryan White clinic; warm handoff prevents loss to follow-up

— Reconcile all interactions (rifamycins, anticonvulsants, PPIs)

CCS pearl: Hospitalized HIV patient with PCP on TMP-SMX who can't tolerate POs and SpO2 drops — order IV TMP-SMX, prednisone taper (40 mg BID × 5d → 40 daily × 5d → 20 daily × 11d), CXR, ABG, and consult ID. Continue or initiate ART within 2 weeks of OI treatment for most OIs (not crypto meningitis).

Inpatient admission criteria for newly diagnosed or known HIV:

ICU triggers:

Specialist consults:

Transitions of care:

Key Differentials — Same-Category Causes (Other Sexually Transmitted/Bloodborne Infections)

— Secondary syphilis: maculopapular rash classically on palms/soles, condyloma lata, mucous patches, generalized LAD, fever — overlaps heavily with acute HIV. Order RPR/VDRL with treponemal confirmation. Coinfection common (~25% of new HIV in MSM); always screen for one when finding the other.

— Acute hepatitis B: fever, malaise, RUQ pain, jaundice, transaminitis. HBsAg, anti-HBc IgM. Same risk profile; vaccinate non-immune HIV-negative contacts.

— Acute hepatitis C: often asymptomatic; ↑ALT, HCV antibody + HCV RNA. Increasing incidence in MSM and PWID.

— Primary HSV: painful genital ulcers, tender inguinal LAD, fever, dysuria; PCR of ulcer. HSV ulcers triple HIV acquisition risk.

— Gonorrhea/Chlamydia (disseminated GC): arthralgias, tenosynovitis, pustular rash, fever — different from HIV rash but shares risk factors. NAAT at all exposed sites.

— Acute EBV/CMV mononucleosis: fever, pharyngitis, LAD, splenomegaly, atypical lymphocytes. Monospot can be negative early; importantly, acute HIV can cause a positive heterophile rarely. The key move: always send HIV testing on every "mono-like" illness in sexually active adults.

— Mpox: febrile prodrome + pleomorphic anogenital/oral lesions in MSM; can coexist with HIV.

— Mucocutaneous ulcers + diffuse rash including trunk + recent unprotected sex → think acute HIV first

— Rash specifically palms/soles + condyloma lata → secondary syphilis

— Jaundice + ↑↑ALT → acute hepatitis

— Painful vesicles/ulcers → HSV or mpox

Board pearl: Finding any new STI is itself an indication to test for HIV and to offer PrEP to HIV-negative patients. Missing the PrEP offer is a recurring wrong path on Step 3.

Acute retroviral syndrome mimics — same exposure category:

Differentiating features to anchor on:

Workup strategy: in any STI evaluation, the answer is almost always panel testing: HIV (4th-gen + RNA if acute), syphilis, HBV, HCV, GC/CT (3-site), trichomonas in women, plus pregnancy test.

Key Differentials — Other-Category Causes (Non-STI Mimics)

— Influenza/COVID-19: fever, myalgia, cough; respiratory symptoms predominate, rash less typical

— Streptococcal pharyngitis: exudative tonsils, no rash unless scarlet fever; rapid strep

— Acute toxoplasmosis (immunocompetent): mononucleosis-like with LAD; Toxoplasma IgM

— Rickettsial illness, dengue, measles, parvovirus B19, rubella: travel/exposure history, specific rash patterns

— Drug reaction (DRESS, serum sickness): medication start within 2–8 weeks, eosinophilia, facial edema

— Adult-onset Still disease: quotidian fevers, salmon rash, very high ferritin, arthritis

— SLE flare: malar rash, ANA, multisystem; can also be associated with low CD4

— Primary immunodeficiencies: CVID, late-onset combined immunodeficiency — recurrent sinopulmonary infections, low immunoglobulins; check quantitative Igs

— Hematologic malignancy (lymphoma, leukemia): B symptoms, cytopenias, LAD

— Disseminated TB or endemic mycoses: weight loss, night sweats, hepatosplenomegaly; can coexist with HIV

— Hyperthyroidism: weight loss, sweats, tachycardia; TSH

— Diabetes: polyuria, polydipsia, weight loss, candidiasis — check fasting glucose/A1c

— Iatrogenic immunosuppression: chronic steroids, biologics, chemotherapy

— Toxoplasmosis: multiple ring-enhancing lesions, basal ganglia, +toxo IgG; respond to empiric therapy

— CNS lymphoma: single periventricular ring-enhancing lesion, +EBV in CSF, thallium-SPECT or PET positive (toxo negative)

— PML: multifocal non-enhancing white matter lesions, JC virus PCR in CSF

— Cryptococcal meningoencephalitis: minimal imaging findings, +CSF CrAg, ↑opening pressure

Key distinction: Empiric treatment for toxoplasmosis with reassessment at 2 weeks is the standard first step for multiple ring-enhancing lesions; failure to improve → brain biopsy for CNS lymphoma. Going to biopsy first is the wrong answer.

Acute HIV mimics not driven by sexual exposure:

Chronic HIV mimics (when constitutional or immunodeficiency picture):

CNS lesion differentials in HIV (key Step 3 contrast):

Secondary Prevention / Long-Term Plan

— Target HIV RNA <50 copies/mL indefinitely

— U=U: durable suppression eliminates sexual transmission and dramatically reduces perinatal risk

— Lifelong ART — never stop without ID consultation

— PCP: TMP-SMX DS daily when CD4 <200; alternatives dapsone (check G6PD), atovaquone, pentamidine

— Toxoplasmosis: TMP-SMX DS daily when CD4 <100 + toxo IgG+

— MAC: no longer routine if immediate ART started; azithromycin weekly if CD4 <50 and ART deferred

— TB: treat latent TB infection — 3HP (rifapentine + INH weekly × 12) or 4R or 9H

— Influenza annually; COVID-19 per CDC schedule

— Pneumococcal series; revaccinate per intervals

— HBV (use double-dose or higher-antigen Heplisav-B if low response); confirm anti-HBs >10

— HPV through 26 (consider through 45)

— Tdap/Td boosters; recombinant zoster (Shingrix) at age ≥19

— Mpox (Jynneos) for at-risk

— Avoid live vaccines if CD4 <200

— Statin (pitavastatin or atorvastatin/rosuvastatin) for most PLWH ≥40 per REPRIEVE-informed practice

— Aggressive BP, A1c, lipid management

— Tobacco cessation — leading modifiable mortality driver in PLWH

— Aspirin for primary prevention only with shared decision-making (general population rules)

— Cervical cytology: at diagnosis, 6 months later, then annually × 3, then q3y if normal (more frequent than general population)

— Anal cytology in MSM, trans women, women with cervical/vulvar dysplasia (ANCHOR trial supports treating high-grade anal dysplasia)

— Standard mammography, colon, lung CT per general guidelines

Board pearl: Tobacco cessation now adds more life-years to a virologically suppressed PLWH than any other intervention. Skipping the smoking cessation discussion is a Step 3 trap.

Viral suppression as the cornerstone:

OI prophylaxis (stop when CD4 sustained above threshold for ≥3–6 months on ART):

Vaccinations ongoing:

Cardiometabolic prevention:

Cancer screening enhancements:

Bone health: DEXA at age 50 or earlier on TDF; calcium/vitamin D

Follow-Up, Monitoring Parameters, and Counseling

— Week 2–4: tolerability, adherence, side effects, mental health

— Week 4–8: HIV RNA (expect ~1-log drop), CMP, CBC

— Every 3 months × first year: HIV RNA, CD4, CMP, CBC

— Every 6 months once suppressed: HIV RNA; CD4 can space to annual or stop once consistently >300–500 with suppression

— Annual: lipids, A1c, UA with protein/creatinine ratio, STI screen, depression screen, substance-use screen, syphilis (q3–6 mo if MSM with ongoing risk)

— Pillboxes, alarms, single-tablet regimens, refill synchronization, 90-day supplies

— Address barriers: cost (ADAP, manufacturer assistance, Ryan White), housing, mental illness, substance use, stigma

— Long-acting injectables for select adherence-challenged patients

— Confirm with repeat VL; assess adherence and interactions first

— Repeat genotype while on failing regimen (must be VL >500–1,000 to amplify)

— Construct new regimen with at least 2 fully active drugs; ID consultation

— U=U reinforcement and disclosure support

— Partner notification: encourage patient referral; if patient unwilling, provider/health department–assisted notification per state law

— Safer sex, condoms, PrEP for HIV-negative partners

— Family planning: safe conception strategies (suppressed VL + timed conception; PrEP for negative partner)

— Mental health, substance use, intimate-partner violence screening

— Aging-related: cognitive concerns, falls, polypharmacy

Step 3 management: Suppressed patient calls after starting antacid for reflux while on bictegravir — counsel to separate by 2 hours (BIC after antacid) or 6 hours (BIC before antacid), or switch to H2 blocker/PPI which are compatible. Don't switch ART reflexively.

Visit cadence after ART initiation:

Adherence support:

Virologic failure workflow:

Counseling at each visit:

CCS-style "what to order" snapshot for routine 6-month visit: HIV RNA, CMP, CBC, fasting lipids/A1c (annual), urine protein/creatinine, STI panel including 3-site GC/CT and RPR, depression screen, medication reconciliation, vaccination review.

Ethical, Legal, and Patient Safety Considerations

— HIV status is protected health information; share only with treating clinicians and as patient authorizes

— Adolescents in most US states may consent to and receive confidential HIV testing/treatment; respect minor's confidentiality while encouraging family support

— Insurance Explanation of Benefits may reveal testing to family — offer alternative billing arrangements or Ryan White clinic

— Encourage patient referral first

— Provider-assisted/Health-department–assisted partner services available in all states — anonymous to index patient

— Many states permit (Tarasoff-style) breach of confidentiality to warn an identifiable partner at imminent risk if the patient refuses to notify and refuses to use protection; consult institutional counsel/health department

— HIV is a reportable condition in all US states (named or coded, varies)

— Suspected child abuse, elder abuse, intimate-partner violence per state requirements

— In some states, knowingly exposing a partner without disclosure can carry criminal penalties — counsel patients factually without moralizing

— Opt-out is the standard — patient informed, can decline; separate written consent no longer required federally (CDC 2006). Some states still require documented verbal consent — know your local rule.

— Cannot test without consent in most circumstances, including comatose patients, unless source testing after occupational exposure under specific state statutes

— Court-ordered testing is rare; sexual assault source-person testing varies by jurisdiction

— Use person-first language ("person living with HIV"), avoid "AIDS patient" or "clean/dirty"

— Address structural inequities driving disparities; integrate harm reduction (needle exchange, MOUD, low-barrier care)

— Discharge with ART in hand, follow-up booked, contact info for case manager; missing a single week of ART can permit resistance and loss to follow-up

— Reconcile drug interactions on every admission (rifampin, anticonvulsants, PPIs, hormonal contraceptives, statins, methadone)

Board pearl: A patient with HIV refuses to disclose to a steady partner and refuses condoms — the correct stepwise answer is counsel, offer health-department–assisted notification, document, and consult ethics/legal. Immediately calling the partner yourself is the wrong answer.

Confidentiality and disclosure:

Partner notification — duty to warn vs confidentiality:

Mandatory reporting:

Informed consent for testing:

Stigma and equity:

Transition-of-care safety:

Occupational exposures: report immediately; institutional protocols for source testing and PEP supersede usual consent rules in many states

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: When a vignette mentions both HBV coinfection and asks for ART selection, the answer always includes tenofovir (TDF or TAF) + emtricitabine or lamivudine — never a regimen that omits dual HBV-active agents.

Screening: USPSTF Grade A, 15–65 once; CDC opt-out 13–64; pregnant women each pregnancy + 3rd-trimester rescreen high-prevalence; PrEP users q3 months.

Test of choice: 4th-generation Ag/Ab combo immunoassay; confirm with HIV-1/2 antibody differentiation; HIV-1 RNA for acute HIV or neonates.

Window period: Ag/Ab ~14–18 days; RNA ~10 days; antibody-only ~3 weeks; full sensitivity by 6 weeks for 4th-gen.

Acute HIV triad: fever + maculopapular rash + mucocutaneous ulcers in sexually active adult.

Oral hairy leukoplakia, Kaposi sarcoma, recurrent zoster in young adult, ITP, seborrheic dermatitis → think HIV.

CD4 thresholds: <500 zoster/candida; <200 PCP; <100 toxo/crypto; <50 CMV/MAC/CNS lymphoma.

PCP: dry cough + hypoxia + bilateral ground-glass + ↑LDH → TMP-SMX + steroids if PaO2 <70 or A-a >35.

Toxoplasmosis vs CNS lymphoma: multiple ring-enhancing → toxo (empiric); single periventricular + EBV in CSF → lymphoma.

PrEP: daily TDF/FTC or TAF/FTC, or cabotegravir IM q2mo; HIV-negative + STI panel + renal function before, then q3 months.

PEP: within 72 h, 28 days of TDF/FTC + INSTI.

Perinatal: ART through pregnancy; VL >1,000 at delivery → C-section + IV ZDV; no breastfeeding in US.

HIV/HBV coinfection: regimen must include TDF/TAF + FTC/3TC.

HLA-B*5701 screen before abacavir.

Dolutegravir raises creatinine (~0.1–0.2) without true injury.

REPRIEVE: statin therapy reduces MACE in PLWH ≥40.

U=U: durable VL <200 → no sexual transmission.

Live vaccines (MMR, varicella, yellow fever): avoid if CD4 <200; Shingrix is recombinant and safe.

Cryptococcal meningitis: defer ART 4–6 weeks to prevent fatal IRIS; serial LPs for ↑ICP.

Reportable: HIV is reportable in all states; partner services available.

Highest-yield modifiable mortality driver in PLWH: tobacco.

Board Question Stem Patterns

3 weeks after a new sexual partner, a 24-year-old has fever, sore throat, trunk rash, oral ulcers, and tender LAD. Monospot negative. Next step? → 4th-gen HIV Ag/Ab + HIV-1 RNA. Wrong answers: repeat monospot, supportive care, EBV serology only.

Reactive 4th-gen Ag/Ab, negative antibody differentiation. Next step? → HIV-1 RNA (NAAT) to diagnose acute HIV. Wrong: repeat Ag/Ab in 6 weeks, Western blot.

Routine adult physical, no stated risk factors. Next step? → Offer HIV testing (opt-out) once between 15–65. Wrong: only test if patient reports risk factors.

36 weeks, VL 8,000. Next step? → Schedule C-section at 38 weeks, give IV zidovudine intrapartum, combination ART for neonate. Wrong: trial of labor, breastfeeding okay.

HIV-negative MSM, new partners, asks about prevention. Next step? → Confirm HIV-negative with Ag/Ab + RNA, baseline renal/HBV/STI, start TDF/FTC daily, follow q3 months.

Hollow-bore stick from HIV+ source on suppressive ART. Next step? → Baseline HIV, start 3-drug PEP within hours, 28-day course, repeat HIV at 6 weeks and 4 months.

47-year-old with thrush, 15-lb weight loss, no stated risk. Next step? → HIV testing. Wrong: empiric fluconazole alone, EGD first.

Patient refuses to tell partner, refuses condoms. Best response? → Counsel, document, offer health-department partner services; involve ethics/legal if persistent refusal with identifiable partner at imminent risk.

HBsAg+ with new HIV. Best regimen? → TDF or TAF + FTC + INSTI (e.g., bictegravir/TAF/FTC). Wrong: DTG/3TC (lacks dual HBV coverage).

Stable patient, Cr 1.0 → 1.2, normal UA. Next step? → Continue therapy, recheck; benign creatinine-secretion blockade.

Step 3 management: When two reasonable answers compete, choose the one that simultaneously diagnoses, prevents transmission, and links to longitudinal care — that triple-purpose answer is almost always correct on HIV stems.

Pattern 1 — "Mono that isn't mono":

Pattern 2 — Indeterminate confirmatory:

Pattern 3 — Opt-out screening:

Pattern 4 — Pregnant patient with detectable VL:

Pattern 5 — PrEP candidate:

Pattern 6 — Needlestick:

Pattern 7 — Oral thrush + weight loss:

Pattern 8 — Confidentiality breach question:

Pattern 9 — HBV coinfection regimen:

Pattern 10 — Creatinine bump on DTG:

One-Line Recap

HIV in primary care is a single integrated competency: screen everyone 13–65 by opt-out 4th-generation Ag/Ab testing (with reflex RNA for acute infection), confirm via the CDC algorithm, link rapidly to integrase-based ART regardless of CD4, prevent transmission with PrEP/PEP/U=U counseling and partner services, and manage HIV as a chronic disease focused on cardiovascular, renal, bone, mental-health, and cancer-prevention outcomes alongside lifelong virologic suppression.

Board pearl: If a Step 3 stem mentions HIV anywhere, ask three questions before answering: Is this diagnosis confirmed and staged? Is transmission being prevented? Is the patient linked to longitudinal care? — the correct answer addresses whichever loop is still open.

Screen and diagnose: USPSTF Grade A 15–65 once + risk-based annually; 4th-gen Ag/Ab → antibody differentiation → HIV-1 RNA for acute; rescreen pregnancy in 3rd trimester.

Treat early, treat everyone: Rapid-start INSTI-based ART (bictegravir/TAF/FTC default); include TDF/TAF + FTC/3TC if HBV coinfected; check HLA-B*5701 before abacavir; defer ART 4–6 weeks only for cryptococcal meningitis.

Prevent transmission: PrEP (daily TDF/FTC, TAF/FTC, or cabotegravir IM) q3-month monitoring; PEP within 72 h for 28 days; perinatal — undetectable by delivery, C-section + IV ZDV if VL >1,000, no breastfeeding in US; partner services via health department.

Manage longitudinally: OI prophylaxis by CD4 (PCP <200, toxo <100, MAC <50 if ART deferred), age-appropriate vaccines (avoid live if CD4 <200; Shingrix safe), statin per REPRIEVE for ≥40, tobacco cessation, cervical/anal cancer screening, depression and SUD screening every visit, and reinforce U=U as both medical truth and stigma-reducing message.