How HIV is tested on Step 1

Each step of the life cycle is a drug target.

Attachmentgp120 binds CD4 + CCR5; maraviroc blocks CCR5Fusiongp41 fuses membranes; enfuvirtide blocks gp41Reverse transcriptionRNA → DNA; NRTIs and NNRTIsIntegrationIntegrase inserts DNA into host genome; -tegravirdrugsAssembly and maturationProtease cleaves gag-pol polyprotein; -navir drugs
HIV life cycle. Reverse transcriptase is error-prone, so resistance develops quickly with single-drug therapy.

Diagnosis and disease course

Which test works depends on timing and age.

  • Acute HIV: 2–4 weeks after exposure; fever, sore throat, rash, lymphadenopathy (mononucleosis-like); very high viral load. Antibody tests may still be negative.
  • Clinical latency: years with few symptoms while CD4 cells steadily fall and the virus replicates in lymph nodes.
  • AIDS: CD4 < 200 cells/µL or an AIDS-defining condition.
  • Infants of mothers with HIV: use nucleic acid (PCR) testing, because maternal IgG crosses the placenta.
  • Monitoring: viral load shows treatment response; CD4 count guides prophylaxis and staging.

Opportunistic infections and cancers

The CD4 count predicts which infections are likely.

CD4 count (cells/µL)Infection or cancerClue
Any countTuberculosis, oral candidiasis (thrush), HSV, VZVTB can occur early
< 200Pneumocystis jirovecii pneumoniaBilateral ground-glass opacities, high LDH; TMP-SMX prophylaxis
< 200Kaposi sarcoma (HHV-8)Purple skin and mucosal lesions
< 150HistoplasmosisFever, weight loss, pancytopenia (Ohio and Mississippi River valleys)
< 100Toxoplasma gondii encephalitisMultiple ring-enhancing lesions
< 100Cryptococcal meningitisIndia ink, cryptococcal antigen
< 100Primary CNS lymphoma (EBV)Single ring-enhancing lesion
< 50Mycobacterium avium complexFever, diarrhea, weight loss
< 50CMV retinitis, colitis, esophagitisCotton-wool retinal lesions; ganciclovir

Progressive multifocal leukoencephalopathy (JC virus) causes white matter lesions without enhancement.

Antiretroviral drugs

Know each class and its signature toxicity.

ART classesNRTIsTenofovir: kidney,bone; abacavir:HLA-B*57:01 reactionNNRTIsEfavirenz: vividdreams; rashIntegraseinhibitorsDolutegravir,bictegravir; firstlineProteaseinhibitorsHyperglycemia,lipodystrophy;CYP3A4
ART classes. Zidovudine causes bone marrow suppression. Pre-exposure prophylaxis (PrEP) uses tenofovir-based regimens.

Worked example

Use the CD4 count and imaging.

functions Worked example — headache and ring-enhancing lesions

A patient with untreated HIV and a CD4 count of 60 cells/µL has headache, fever, and confusion. MRI shows multiple ring-enhancing lesions in the basal ganglia. Toxoplasma IgG is positive. What is the diagnosis and treatment?

  1. At a CD4 count below 100, toxoplasmosis and primary CNS lymphoma are the main causes of ring-enhancing lesions.
  2. Multiple lesions and positive Toxoplasma serology favor toxoplasmosis; lymphoma is usually a single lesion.
  3. Treatment is pyrimethamine plus sulfadiazine, with leucovorin to protect the marrow.
  4. Lack of improvement in about 2 weeks would prompt biopsy for lymphoma.

Answer. Toxoplasma encephalitis; pyrimethamine, sulfadiazine, and leucovorin. TMP-SMX prophylaxis would have prevented it.