Infectious Disease · PANCE / PANRE

HIV / AIDS

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

Chronic retroviral infection of CD4 T-cells leading to progressive immunodeficiency; managed with lifelong combination antiretroviral therapy.

Also known as: HIV, AIDS, human immunodeficiency virus, acquired immunodeficiency syndrome

Overview

Infection with HIV-1 or HIV-2, single-stranded RNA retroviruses that bind CD4 and CCR5/CXCR4 to infect helper T-cells, monocytes, and dendritic cells. AIDS is defined as HIV infection plus CD4 count <200 cells/uL or the presence of an AIDS-defining illness.

Epidemiology

Approximately 1.2 million people in the US live with HIV; roughly 13% are undiagnosed. New infections concentrated among men who have sex with men, injection drug users, and Black and Latino populations in the South. HIV-1 dominates worldwide; HIV-2 largely restricted to West Africa.

Try two board-style HIV / AIDS questions

Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.

Question 1Infectious DiseaseMedium
A 35-year-old male healthcare worker sustains a needlestick from a patient known to be HIV positive (viral load 50,000 copies/mL). Exposure occurred 2 hours ago. Which of the following is the most appropriate post-exposure prophylaxis?
  • ATenofovir/emtricitabine/efavirenz for 28 days
  • BTenofovir/emtricitabine plus dolutegravir for 28 days
  • CTenofovir/emtricitabine plus darunavir/ritonavir for 28 days
  • DZidovudine/lamivudine plus nevirapine for 28 days
Reveal answer & full explanation
Correct answer: B — Tenofovir/emtricitabine plus dolutegravir for 28 days
  • ATenofovir/emtricitabine/efavirenz for 28 days
  • BTenofovir/emtricitabine plus dolutegravir for 28 days✓
  • CTenofovir/emtricitabine plus darunavir/ritonavir for 28 days
  • DZidovudine/lamivudine plus nevirapine for 28 days

Why tenofovir/emtricitabine plus dolutegravir for 28 days is correct

  • HIV post-exposure prophylaxis (PEP) should start as soon as possible, ideally within 2 hours and no later than 72 hours post-exposure
  • Transmission risk from a needlestick of an HIV+ source is approximately 0.3% without PEP; PEP reduces transmission by approximately 80%
  • Preferred regimen: tenofovir DF/emtricitabine (Truvada) plus raltegravir or dolutegravir for 28 days

Why the others are wrong

  • A) Tenofovir/emtricitabine/efavirenz for 28 days — efavirenz-based regimens are no longer preferred due to neuropsychiatric side effects
  • D) Zidovudine/lamivudine plus nevirapine for 28 days — nevirapine is avoided for PEP because of hepatotoxicity
  • C) Tenofovir/emtricitabine plus darunavir/ritonavir for 28 days — darunavir/ritonavir is an alternative anchor but is not the preferred agent

Additional high-yield points

  • Follow-up HIV testing at 6 weeks, 3 months, and 6 months
Question 2Infectious DiseaseMedium
A 28-year-old man who has sex with men asks about HIV pre-exposure prophylaxis. He is HIV-negative. His partner has HIV with an undetectable viral load on treatment. Which of the following regimens is most appropriate?
  • ADaily tenofovir disoproxil fumarate/emtricitabine
  • BDaily tenofovir/emtricitabine/dolutegravir
  • CLong-acting injectable rilpivirine every 2 months
  • DOn-demand (2-1-1) tenofovir/emtricitabine dosing
Reveal answer & full explanation
Correct answer: A — Daily tenofovir disoproxil fumarate/emtricitabine
  • ADaily tenofovir disoproxil fumarate/emtricitabine✓
  • BDaily tenofovir/emtricitabine/dolutegravir
  • CLong-acting injectable rilpivirine every 2 months
  • DOn-demand (2-1-1) tenofovir/emtricitabine dosing

Why daily tenofovir disoproxil fumarate/emtricitabine is correct

  • Daily oral TDF/FTC (Truvada) provides >99% efficacy in adherent MSM (iPrEx trial)
  • It is the established first-line oral PrEP regimen in US CDC guidance

Why the others are wrong

  • B) Daily tenofovir/emtricitabine/dolutegravir — three-drug daily regimens are HIV treatment, not prophylaxis
  • C) Long-acting injectable rilpivirine every 2 months — rilpivirine LAI is for HIV treatment (combined with cabotegravir as Cabenuva), not PrEP
  • D) On-demand (2-1-1) tenofovir/emtricitabine dosing — endorsed by some international guidelines for MSM but is not first-line in US CDC guidance

Additional high-yield points

  • Daily oral TAF/FTC (Descovy) is an alternative PrEP option for MSM and transgender women with better bone/renal safety
  • Long-acting injectable cabotegravir (Apretude, every 2 months) is superior to daily oral TDF/FTC in HPTN 083/084 trials
  • U=U (Undetectable = Untransmittable): when an HIV+ partner has sustained undetectable viral load, transmission risk is effectively zero, but PrEP is still recommended for HIV-negative partners who wish additional protection
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Risk factors

  • Receptive anal intercourse (highest per-act risk)
  • Multiple sex partners, condomless sex, concurrent STI (especially ulcerative — syphilis, HSV)
  • Injection drug use with shared needles
  • Vertical transmission (in utero, intrapartum, breastfeeding) — risk reduced from ~25% to <1% with maternal ART
  • Occupational needlestick (per-exposure risk ~0.3% for hollow-bore blood exposure)
  • Blood transfusion in regions without universal screening

Pathophysiology

Envelope gp120 binds CD4 and a coreceptor (CCR5 in early infection, CXCR4 later), allowing gp41-mediated fusion and viral entry. Reverse transcriptase produces proviral DNA that integrates into the host genome via integrase. Ongoing replication depletes CD4 cells, disrupts lymph node architecture, and causes chronic immune activation. Untreated, CD4 declines ~50-100 cells/uL/year; opportunistic infections appear as immunity fails.

Clinical presentation

Symptoms

  • Acute retroviral syndrome (2-4 weeks post-exposure): fever, pharyngitis, lymphadenopathy, maculopapular trunk rash, myalgia, headache, oral ulcers
  • Clinical latency phase: asymptomatic for years, possibly persistent generalized lymphadenopathy
  • Symptomatic stage (CD4 200-500): oral thrush, recurrent zoster, seborrheic dermatitis, oral hairy leukoplakia, unexplained weight loss
  • AIDS (CD4 <200 or AIDS-defining illness): PCP pneumonia, esophageal candidiasis, toxoplasmosis, CMV retinitis, MAC, cryptococcal meningitis, PML, Kaposi sarcoma, NHL

Signs / physical exam

  • Generalized lymphadenopathy, hepatosplenomegaly
  • Oral candidiasis (white plaques scrapable from buccal mucosa/tongue)
  • Wasting, temporal muscle atrophy in advanced disease
  • Cutaneous KS — violaceous nodules/plaques; molluscum-like facial lesions

Classic findings

Acute mononucleosis-like illness 2-4 weeks after high-risk exposure, often with a non-pruritic trunk rash, should prompt HIV RNA testing even if antibody screening is negative.

Differential diagnosis

  • Acute viral syndrome (EBV, CMV, acute hepatitis) — Acute retroviral syndrome mimics mononucleosis; obtain HIV RNA viral load (turns positive ~10 days) — antibody tests miss the window period
  • Secondary syphilis — Diffuse maculopapular rash including palms/soles, mucous patches, condyloma lata; RPR/VDRL plus treponemal test
  • Disseminated gonococcal infection — Migratory polyarthralgia, tenosynovitis, pustular skin lesions; blood and mucosal cultures
  • Lymphoma — Persistent lymphadenopathy, B symptoms; biopsy required — HIV-associated lymphomas common at low CD4
  • Idiopathic CD4 lymphocytopenia — Low CD4 with negative HIV tests; rare diagnosis of exclusion
  • Tuberculosis — Coinfection extremely common worldwide; screen all newly diagnosed HIV with IGRA or TST and CXR

Diagnostic workup

Diagnostic criteria

CDC algorithm: reactive Ag/Ab combo assay confirmed by HIV-1/2 differentiation assay. Discordant or early-infection cases resolved with HIV RNA. AIDS = HIV plus CD4 <200 cells/uL or any stage-3 AIDS-defining condition.

Labs

  • 4th-generation HIV-1/2 antigen-antibody combination immunoassay (detects p24 antigen and antibodies; positive ~2-3 weeks post-infection)
  • Confirmatory HIV-1/2 antibody differentiation assay (Geenius); if negative or indeterminate, HIV-1 RNA PCR
  • Baseline CD4 count and percentage, HIV RNA viral load, genotypic resistance testing
  • HLA-B*5701 prior to abacavir; tropism assay if maraviroc considered
  • Screen for coinfections: HBV (HBsAg, anti-HBs, anti-HBc), HCV antibody with reflex RNA, syphilis (RPR), gonorrhea/chlamydia at all exposed sites, latent TB (IGRA), toxoplasma IgG, CMV IgG, varicella IgG
  • CBC, CMP, lipid panel, A1c, UA, pregnancy test, G6PD if dapsone planned

Imaging

  • Baseline CXR for TB screening
  • Dilated funduscopy if CD4 <50 to screen for CMV retinitis
  • CT/MRI brain if focal neuro findings (toxoplasmosis, PML, CNS lymphoma, cryptococcoma)

Diagnostic algorithm

CD4 (cells/uL)Common Opportunistic InfectionsRecommended Prophylaxis
>500Acute retroviral syndrome, candidal vaginitis, herpes zosterNone routine; vaccinate
200-500Oral thrush, oral hairy leukoplakia, Kaposi sarcoma, TB reactivationTreat latent TB if positive
<200PCP, esophageal candidiasis, cryptococcal meningitisTMP-SMX for PCP
<100Toxoplasma encephalitis, cryptosporidiosis, microsporidiosisTMP-SMX (covers PCP + Toxo)
<50CMV retinitis/colitis, MAC, CNS lymphoma, PMLDefer MAC prophylaxis if rapid ART; screen retina
CD4-stratified opportunistic infections and prophylaxis thresholds in HIV/AIDS.

Treatment

First-line

  • Initiate ART at diagnosis regardless of CD4 (START and TEMPRANO trials)
  • Preferred regimens (DHHS): INSTI + 2 NRTI backbone
  • INSTI (HIV integrase inhibitor) — bictegravir, dolutegravir, raltegravir
  • NRTI backbone — tenofovir alafenamide (TAF)/emtricitabine, tenofovir disoproxil fumarate (TDF)/emtricitabine, abacavir/lamivudine (only if HLA-B*5701 negative)
  • Single-tablet options: bictegravir/TAF/emtricitabine (Biktarvy); dolutegravir/abacavir/lamivudine (Triumeq, HLA-B*5701 negative only); dolutegravir + lamivudine (Dovato) for naive patients with VL <500,000 and no HBV
  • Long-acting injectable cabotegravir + rilpivirine IM every 1-2 months for virologically suppressed patients

Pre-exposure prophylaxis (PrEP)

  • Daily oral TDF/emtricitabine (Truvada) or TAF/emtricitabine (Descovy; not for receptive vaginal exposure)
  • Long-acting injectable cabotegravir IM every 2 months (Apretude)
  • On-demand 2-1-1 TDF/FTC dosing for MSM in select settings
  • Repeat HIV testing every 3 months; STI and renal monitoring

Post-exposure prophylaxis (PEP)

  • Initiate within 72 hours of exposure; 28-day course
  • Preferred: tenofovir/emtricitabine + dolutegravir or raltegravir
  • Baseline and follow-up HIV testing at 4-6 weeks and 3 months (4th gen assay)

Opportunistic infection prophylaxis

  • PCP (CD4 <200 or oral thrush): TMP-SMX; alternatives dapsone, atovaquone, pentamidine
  • Toxoplasmosis (CD4 <100 + positive IgG): TMP-SMX
  • MAC (CD4 <50): historically azithromycin; current DHHS recommends deferral if ART started promptly
  • Latent TB: isoniazid + B6 for 9 months, or rifapentine/INH weekly for 12 weeks (3HP)

Second-line / adjunct

  • Protease inhibitor (boosted) — darunavir/ritonavir or darunavir/cobicistat for resistance or pregnancy
  • NNRTI — doravirine, rilpivirine, efavirenz (efavirenz historically avoided in first trimester pregnancy planning)
  • CCR5 antagonist — maraviroc (requires tropism testing)
  • Fusion inhibitor — enfuvirtide; attachment inhibitor — fostemsavir; post-attachment — ibalizumab (salvage therapy)

Complications

  • Opportunistic infections (PCP, toxoplasmosis, cryptococcus, CMV, MAC, TB)
  • AIDS-defining malignancies — Kaposi sarcoma, non-Hodgkin lymphoma, invasive cervical cancer
  • HIV-associated neurocognitive disorder (HAND)
  • Immune reconstitution inflammatory syndrome (IRIS) within weeks of starting ART
  • Accelerated atherosclerosis, CKD (especially with TDF), osteoporosis, metabolic syndrome

PANCE pearls

  • Acute HIV: antibody-based tests can be negative in the window period — order HIV RNA viral load.
  • Pregnancy: dolutegravir is now preferred throughout pregnancy (early neural tube signal not confirmed). Avoid TAF in late pregnancy data-poor scenarios; TDF/FTC + dolutegravir is well-validated.
  • U = U: undetectable equals untransmittable. Sustained viral suppression eliminates sexual transmission risk (PARTNER, PARTNER2, Opposites Attract trials).
  • CD4 <200 → start PCP prophylaxis. CD4 <100 with positive toxo IgG → add toxoplasmosis prophylaxis (TMP-SMX covers both).
  • Cryptococcal meningitis: opening pressure is therapeutic — serial LPs reduce mortality more than any antifungal change.

References

  • DHHS 2024 — Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV (clinicalinfo.hiv.gov)
  • CDC 2014 — Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations (MMWR)
  • START Trial — Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (NEJM 2015)
  • PARTNER2 — Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (Rodger et al., Lancet 2019)

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Lyme DiseaseRocky Mountain Spotted Fever (RMSF)Infectious Mononucleosis (EBV)Cytomegalovirus (CMV)Sepsis and Septic ShockCellulitisErysipelasNecrotizing FasciitisTetanusRabies Post-Exposure ProphylaxisMalariaToxoplasmosisGiardiasisCryptosporidiosis

Differentials & related conditions

Tuberculosis (Active and Latent)

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