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Microbiology · Immunodeficiency

HIV Diagnosis
and Antiretroviral Management

Three switches decide most HIV clinical questions: which test catches the window period, when to start antiretroviral therapy (ART), and what prophylaxis the CD4 count unlocks. This page pairs with the opportunistic-infections ladder; here we teach diagnosis and treatment.

Medically reviewed by Fatima Ali, DO & Kaitlyn Cocuzzo, MD

Before you scroll
A 22-year-old man comes to the student health clinic because of 12 days of fever, sore throat, and a diffuse maculopapular rash. He reports unprotected sex with a new partner four weeks ago. Temperature is 39.1 C (102.4 F), blood pressure is 116/70 mmHg, and heart rate is 108/min. Physical examination shows posterior cervical lymphadenopathy and a faint truncal rash. A heterophile antibody (monospot) test is negative. Laboratory studies show white blood cell count 3,400/microL (4,500 to 11,000). Which of the following is the most appropriate next step in diagnosis?
What pattern is this?
Fever, pharyngitis, rash, and lymphadenopathy mimic mononucleosis, but heterophile-negative mononucleosis-like illness with recent high-risk exposure is acute retroviral syndrome.
Why not wait on antibody testing?
Fourth-generation screens detect p24 antigen plus antibodies, but the first ~2 weeks can still be antibody-negative. During the window, HIV RNA catches infection when antibodies have not formed yet.
Scroll ↓ the testing algorithm comes next
Diagnosis
Walk the Testing Algorithm
Tap each branch. Positive fourth-generation screen reflexes to differentiation. Suspected acute infection during the window needs HIV RNA.
The window period, visualized
0d 10d 20d 30d 40d Exposure day 0 HIV RNA (NAAT) ~10d · catches acute infection p24 antigen ~16d · 4th-gen screen positive Antibodies ~22d · 3rd-gen screen positive days after exposure ↓
Gold zone is the window period: the 4th-gen screen can still read negative. HIV RNA turns positive first, so it is the test that catches acute infection before antibodies form.
The static ladder
1
Fourth-generation Ag/Ab comboDetects p24 capsid antigen plus HIV-1 and HIV-2 antibodies. This is the screening test.
2
HIV-1/HIV-2 differentiation immunoassayPositive screen reflexes here to confirm type before calling it HIV.
3
HIV RNA (NAAT or viral load)Suspected acute infection or window period when antibodies are not yet detectable. Quantitative viral load also monitors treatment and transmissibility.
What You See at the Bedside
Oral and Skin Clues
These findings push you toward immunosuppression. Full CD4 opportunistic infection teaching lives on the dedicated opportunistic-infections page.
Oral candidiasis (thrush)

White plaques on the tongue or buccal mucosa that scrape off and may bleed. Common when CD4 falls and local immunity weakens.

Oral candidiasis on the tongue
Oral candidiasis
Oral hairy leukoplakia (EBV-related)

EBV-related hairy leukoplakia is white lateral-tongue plaque that does not scrape off. Differentiate from thrush by the scrape test.

White oral plaque consistent with leukoplakia teaching image
White oral plaque (teaching image)
Kaposi sarcoma (HHV-8)

Violaceous skin or mucosal lesions linked to human herpesvirus 8 in advanced immunosuppression. Biopsy confirms when the stem shows a new purple plaque.

Kaposi sarcoma skin lesions
Kaposi sarcoma
Treatment
ART for Everyone
Start antiretroviral therapy at diagnosis regardless of CD4. Preferred initial regimen: two NRTIs plus an integrase inhibitor.
Tenofovir + emtricitabine + dolutegravir (or bictegravir-based STR)
Two nucleoside reverse transcriptase inhibitors (NRTIs) backbone plus an integrase strand transfer inhibitor (INSTI). Goal: undetectable viral load. Undetectable equals untransmittable.
Strongest indications to start now?
AIDS-defining illness, CD4 under 500 cells/microL, or high viral load. Still, current standard is start ART for everyone at diagnosis.
Pregnancy?
ART throughout pregnancy. Zidovudine (ZDV) in pregnancy reduces vertical transmission. Continue ART postpartum.
HIV-2 trap?
NNRTIs and enfuvirtide are not effective against HIV-2. Integrase-based regimens remain preferred when treating HIV-2.
What is IRIS?
Immune reconstitution inflammatory syndrome: paradoxical worsening of a pre-existing infection (for example MAC or TB) as CD4 recovers after ART starts. Do not stop ART solely for IRIS without expert input.
Prevention
PrEP: tenofovir + emtricitabine for ongoing risk.
PEP: TDF + FTC + raltegravir or dolutegravir for 28 days; start within 72 hours of exposure; test baseline, 6 weeks, 3 months, and 6 months.
Bridge to Opportunistic Infections
CD4 Prophylaxis Thresholds
Compact reference only. The full opportunistic infection ladder and AIDS-defining illnesses live on the dedicated page.
<200TMP-SMX for PCP prophylaxis
<100TMP-SMX also covers Toxoplasma prophylaxis
<50Add azithromycin for MAC prophylaxis

Full CD4 opportunistic infection ladder →

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