INFECTIOUS SYNDROMES

Human Immunodeficiency Virus and AIDS

Classification: Acquired retroviral immunodeficiency with progressive CD4 T-cell depletion and immune dysregulation (Kishiyama et al., 2019).

Key diagnostic discriminator: HIV is diagnosed by the recommended test sequence. AIDS is advanced HIV defined by CD4 count below 200 cells/mm3, CD4 percentage below 14%, or an AIDS-defining condition (Kishiyama et al., 2019).

Clinical priority: Suspected acute HIV, pregnancy, neurologic symptoms, respiratory compromise, severe headache, focal deficit, or signs of opportunistic disease require expedited evaluation (Kishiyama et al., 2019).

Etiology and risk factors

  • HIV-1 is the predominant cause. Transmission occurs through sexual exposure, blood exposure including shared injection equipment, and perinatal/breastfeeding routes (Kishiyama et al., 2019).
  • Risk reflects type and frequency of exposure, viral load, mucosal integrity, coexisting sexually transmitted infection, use of prevention, and treatment status of the source (Kishiyama et al., 2019).

Pathophysiology

  • Viral gp120 binds CD4 and a chemokine coreceptor, usually CCR5 early and sometimes CXCR4 later. Fusion, reverse transcription, integration, transcription, assembly, and budding establish productive and latent infection (Kishiyama et al., 2019).
  • Ongoing replication and immune activation destroy or impair CD4 T cells in blood and lymphoid tissue. Progressive loss of cell-mediated immunity permits opportunistic infection, malignancy, and inflammatory organ injury (Kishiyama et al., 2019).

Clinical manifestations

  • Acute retroviral syndrome 2–4 weeks after acquisition may cause fever, rash, pharyngitis, lymphadenopathy, myalgia, diarrhea, headache, or aseptic meningitis; it may also be asymptomatic (Kishiyama et al., 2019).
  • Chronic infection may be clinically silent for years. Later findings include weight loss, persistent fever/night sweats, chronic diarrhea, oral candidiasis, recurrent infection, cytopenias, neurologic disease, opportunistic infection, and malignancy (Kishiyama et al., 2019).
  • The opportunistic-disease pattern tracks immune decline: Pneumocystis risk rises with CD4 below 200; toxoplasmosis with severe decline; disseminated Mycobacterium avium complex or cytomegalovirus typically occurs with very low counts (Kishiyama et al., 2019).

Findings that argue against or redirect

  • A negative antibody-only test during the window period does not exclude acute HIV. Use antigen/antibody and nucleic-acid testing based on exposure timing and symptoms (Kishiyama et al., 2019).
  • A positive screening assay requires a supplemental confirmatory test (Kishiyama et al., 2019).
  • Normal CD4 count does not exclude HIV, and an undetectable treated viral load does not mean that infection has been eradicated (Kishiyama et al., 2019).

Diagnostic evaluation

  • Use a laboratory-based HIV-1/2 antigen-antibody assay as the initial test, followed by an HIV-1/HIV-2 antibody differentiation assay when reactive. Use HIV RNA testing when acute infection is suspected or results are discordant because viremia can precede detectable antibody (Kishiyama et al., 2019; Panel on Antiretroviral Guidelines for Adults and Adolescents, 2026).
  • After diagnosis, obtain viral load, CD4 count and percentage, resistance testing, and baseline evaluation for coinfection, organ dysfunction, pregnancy, medication interactions, and opportunistic disease suggested by the presentation (Kishiyama et al., 2019; Panel on Antiretroviral Guidelines for Adults and Adolescents, 2026).

Expected diagnostic and laboratory findings

  • Acute infection can show HIV RNA and/or p24 antigen before antibodies fully develop. Established infection generally produces a reactive antigen-antibody screening result followed by a positive supplemental confirmatory result (Kishiyama et al., 2019).
  • Viral load measures replication and treatment response. CD4 count and percentage estimate immune function and help anticipate opportunistic disease (Kishiyama et al., 2019).
  • AIDS is a staging category; a person remains classified as having had AIDS even if treatment later raises the CD4 count and suppresses viral replication (Kishiyama et al., 2019).

Differential diagnosis

  • Infectious mononucleosis, influenza, viral hepatitis, and secondary syphilis can mimic acute retroviral syndrome; HIV testing resolves the concern (Kishiyama et al., 2019).
  • Primary immunodeficiency usually presents earlier and lacks acquired HIV markers (Kishiyama et al., 2019).
  • Medication, malignancy, malnutrition, or severe illness can reduce CD4 counts but does not produce a diagnostic HIV test sequence (Kishiyama et al., 2019).

Treatment and management

  • Recommend antiretroviral therapy for every person with HIV and initiate it immediately or as soon as possible after diagnosis. Specific opportunistic infections, including cryptococcal or tuberculous meningitis, may require modified timing to reduce serious inflammatory complications and warrant specialist coordination (Kishiyama et al., 2019; Norris, 2020; Panel on Antiretroviral Guidelines for Adults and Adolescents, 2026).
  • Obtain baseline resistance testing, but do not routinely delay treatment while awaiting results in acute HIV when an appropriate initial regimen can be selected. Account for prior long-acting preexposure prophylaxis and other circumstances that increase the likelihood of resistance (Kishiyama et al., 2019; Norris, 2020; Panel on Antiretroviral Guidelines for Adults and Adolescents, 2026).
  • Select the regimen according to resistance, comorbidities, kidney and liver function, pregnancy potential, drug interactions, adverse-effect profile, and patient preference. Address adherence and access barriers before and after initiation (Kishiyama et al., 2019; Norris, 2020; Panel on Antiretroviral Guidelines for Adults and Adolescents, 2026).
  • Treat and prevent opportunistic infections according to the specific pathogen and immune status. Monitor viral load, CD4 count when indicated, treatment toxicity, interactions, and clinical complications (Kishiyama et al., 2019; Norris, 2020; Panel on Antiretroviral Guidelines for Adults and Adolescents, 2026).

Additional complications and red flags

  • Severe opportunistic infection requires disease-specific management and specialist coordination (Kishiyama et al., 2019).

Content last reviewed:

References

Kishiyama, J. L., Chang, J. J., & Donovan, S. M. (2019). Disorders of the immune system. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.

Panel on Antiretroviral Guidelines for Adults and Adolescents. (2026). Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. U.S. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv