HIV Presentation

Aka: HIV Presentation, Acute Retroviral Syndrome, Acute HIV Infection, HIV New Diagnosis, Primary HIV Infection

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II. Precautions

  1. Primary infection is asymptomatic or unrecognized in >50% of cases
    1. At least 12% of patients are unaware they are infected
    2. Acutely infected patient is high risk of transmission
    3. More than one third of new HIV Transmission is from sources who are unaware they are HIV positive
    4. Early diagnosis allows for ART and transmission prevention (including PREP and Postexposure Prophylaxis)
    5. Li (2019) MMWR Morb Mortal Wkly Rep 68(11): 267-72 [PubMed]
  2. Despite HIV Antiretroviral therapy high efficacy (see below), it is underutilized
    1. Only half of the 1.2 million patients with HIV in U.S. (2015) were adequately treated with Antiretrovirals
    2. Woodring (2015) Natl Health Stat Report (83):1-13 [PubMed]

III. History

  1. See HIV Risk Screening Questions
  2. See HIV Risk Factors

IV. Findings: Typical Presentation

  1. Mononucleosis-like illness
  2. Occurs 2-3 weeks after exposure in up to 90% of patients
  3. Precedes seroconversion by 10-21 days
  4. Self limited
  5. Medical attention sought in 20-30% of patients

V. Findings: Acute Retroviral Syndrome

  1. Fever (low-grade <102) occurs in 80-90%
    1. Fever over 102 with rigors suggests occult infection
  2. Fatigue (70-90%)
  3. Erythematous Maculopapular Rash (40-80%)
    1. Face and Trunk
    2. Extremities involving palms and soles
  4. Headache (32-70%)
  5. Generalized Lymphadenopathy (40-70%)
  6. Pharyngitis (50-70%)
  7. Myalgia or Arthralgia (50-70%)
  8. Gastrointestinal symptoms (30-60%)
    1. Nausea or Vomiting
    2. Diarrhea
  9. Hepatosplenomegaly (14%)
  10. Night Sweats (50%)
  11. Oral Aphthous Ulcers or Thrush (10-20%)
  12. Genital Ulcers (5-15%)
  13. Neurologic symptoms (12%)
    1. Aseptic Meningitis (25%)
    2. Peripheral Neuropathy
    3. Facial palsy
    4. Guillain-Barre Syndrome
    5. Brachial Neuritis
    6. Cognitive Impairment
    7. Psychosis
  14. Malaise
  15. Anorexia
  16. Weight loss (70%)
  17. Wasting Syndrome
    1. Unexplained Weight Loss of >10% usual body weight

VI. Evaluation: Initial

  1. What is the current risk of HIV progression?
    1. Based on CD4 Count and HIV Viral Load
    2. Are Antiretrovirals indicated at this point?
      1. Antiretrovirals are now recommended regardless of CD4 Count and HIV Viral Load
  2. What is the current risk of opportunistic infection?
    1. Based on CD4 Count and comorbid conditions
    2. Is prophylaxis or screening indicated?
      1. See HIV Prophylaxis of Secondary Infection
  3. What symptoms are present related to HIV status?
    1. Acute Retroviral Syndrome
    2. Manifestations suggesting advanced HIV (and severe Immunosuppression)
      1. See AIDS Defining Illness and HIV Course
  4. Identify comorbid conditions related to HIV Infection
    1. Sexually Transmitted Infections (e.g. Gonorrhea, Chlamydia, Syphilis)
    2. Viral Hepatitis (e.g. Hepatitis B, Hepatitis C)
    3. Substance Abuse
    4. Sexual practices (highest risk in Men who have Sex with Men)
  5. Identify Health Maintenance needs and other serious comorbidities
    1. Routine preventive care as indicated (e.g. Pap Smear, Mammogram, skin exam, Colonoscopy)
    2. Diabetes Mellitus
    3. Hypertension or Hyperlipidemia
    4. Major Depression

VII. Imaging: Chest XRay Indications

  1. Pulmonary symptoms on presentation or
  2. Tuberculin Skin Test positive

VIII. Labs: HIV Diagnosis

  1. See HIV Screening for Lab protocol

IX. Labs: Initial labs at time of diagnosis

  1. Labs often abnormal at diagnosis
    1. Complete Blood Count with Platelet Count
      1. Thrombocytopenia (45%)
      2. Leukopenia (40%)
    2. Liver Function Tests
      1. Hepatic enzyme (transaminase) levels may be elevated
  2. Baseline labs prior to starting medications
    1. Serum Creatinine
    2. Serum Glucose
    3. Lipid profile (affected by Protease Inhibitors)
    4. Urinalysis
    5. Pregnancy Test
      1. See HIV in Pregnancy
  3. HIV Staging labs
    1. CD4 Count
      1. Best marker of HIV-related Immunosuppression, infection duration and prognosis
      2. Varies from person to person, lab to lab, by time of day, and most significantly by acute comorbid illness
    2. Plasma HIV RNA level or Viral load
      1. See Protocol above
      2. Obtain 2 assays at 1-2 weeks apart
    3. Genotypic Antiretroviral Resistance Testing
      1. Test at baseline to direct Antiretrovirals
      2. Requires a viral load above lab cutoffs (typically >500/ml)
  4. Screen for infections prior to Immunization
    1. Hepatitis B Surface Antigen (HBsAg)
    2. Hepatitis A Serology (xHAV IgG)
  5. Screen for comorbid illness and Immunity
    1. Hepatitis C Antibody (xHCV)
    2. Rapid Plasma Reagin (RPR)
    3. Toxoplasmosis IgG
    4. Cytomegalovirus IgG (CMV IgG)
    5. Neisseria gonorrhoeae PCR
    6. Chlamydia Trachomatis PCR
    7. Tuberculosis Testing
      1. Tuberculin Skin Test (PPD) with >5mm positive in HIV, or
      2. Interferon Gamma Release Assay (Quantiferon Gold)
    8. Varicella IgG (VZV IgG)
      1. Test before Post-exposure Prophylaxis

X. Monitoring: HIV Specific

  1. CD4 Count
    1. Initial
      1. Baseline (as above), then
      2. At 3 months after starting Antiretroviral therapy, then
      3. Repeat every 3-6 months for first 2 years
    2. After first 2 years
      1. CD4 >300 cells/mm3 for 2 years with suppressed viral load
        1. Obtain CD4 Count every 12 months
      2. CD4 >500 cells/mm3 for 2 years with suppressed viral load
        1. CD4 Count testing optional
  2. HIV Viral Load
    1. Baseline, then
    2. At 2-8 weeks after starting Antiretroviral therapy, then
    3. Repeat every 4-8 weeks until viral load <200 copies/ml, then
    4. Repeat every 3 to 6 months while viral load <200 copies/ml
  3. Antiretroviral drug therapy related testing
    1. Genotypic Antiretroviral Resistance Testing
      1. Baseline, then
      2. As indicated per therapy response
      3. Consider integrase resistance testing
    2. Other testing to consider
      1. G6PD Deficiency (risk of Septra or Dapsone induced Hemolytic Anemia)
      2. HLA-B*5701 (risk of Abacavir reaction)

XI. Monitoring: Other testing

  1. Annual screening
    1. PPD Skin Test and Chest XRay
    2. Pap Smear
      1. Obtain every 6-12 months, then if 3 results normal, every 3 years
      2. HPV Testing after 30 years old
    3. Anorectal Exam (anal warts, Anal Cancer, Sexually Transmitted Infection)
    4. Anal cytology (anal Pap Smear)
      1. Not typically recommended aside from high risk men (esp. anal condyloma)
  2. Other annual tests depending on risks
    1. Rapid Plasma Reagin (RPR)
    2. Gonorrhea Antigen
    3. Chlamydia Antigen
    4. Hepatitis C Serology
    5. Hepatitis B Serology
    6. Toxoplasma IgG
  3. Periodic comorbidity screening depending on risks
    1. Complete Blood Count with Platelets
      1. Every 3 to 6 months
    2. Comprehensive metabolic panel (renal and liver function)
      1. Baseline, then
      2. At 2-8 weeks after starting Antiretroviral therapy, then
      3. Every 3 to 6 months
      4. Also monitor phosphate while on Tenofovir disoproxil Fumarate
    3. Urinalysis
      1. Obtain yearly (or every 6 months if on Tenofovir disoproxil Fumarate)
  4. Testing if CD4 Count <100 cells/mm3
    1. Acid Fast BacteriaBlood Culture for MAI Complex
    2. Dilated Funduscopic Exam for CMV q3-6 months

XII. Differential Diagnosis

  1. HIV related disease
    1. Occult infection (especially if CD4 Count< 200 cells)
    2. Anti-microbial agents (Drug Reaction in HIV)
      1. Most frequent cause of Drug Induced Fever
  2. Most Common
    1. Epstein-Barr Virus Infection (Mononucleosis)
    2. Influenza
    3. Severe Streptococcal Pharyngitis
    4. Viral Gastroenteritis
    5. Viral upper respiratory tract infection
  3. Less Common
    1. Drug Reaction
    2. Primary Herpes Simplex Virus Infection
    3. Viral Hepatitis
    4. Secondary Syphilis
  4. Least Common
    1. Aseptic Meningitis
    2. Primary Cytomegalovirus infection (CMV)
    3. Toxoplasmosis
    4. Rubella
    5. Brucellosis
    6. Measles
    7. Malaria
    8. Typhoid

XIII. Management

  1. See HIV Course
  2. See HIV Treatment Strategy
  3. See Combination Antiretroviral Therapy (CART)
  4. Consult with HIV specialist to start management
  5. Consult social services, case management and HIV education
  6. Starting Antiretrovirals is usually not urgent
    1. Combination Antiretroviral Therapy (CART) is recommended as of 2014
    2. Early treatment and prevention (regardless of CD4 Count)
  7. Initial agents should be chosen carefully
    1. Genotypic Antiretroviral Resistance Testing is typically indicated prior to starting Antiretroviral agents
    2. Best response to therapy is with the first attempt
    3. Informed Consent for longterm compliance is critical
    4. Identify and manage barriers to compliance

XIV. Prevention: Strategies at Diagnosis

  1. See HIV Prophylaxis of Secondary Infection
  2. Acute Retroviral Syndrome is high risk of transmission (10 fold increased risk)
    1. Peak viremia occurs with Acute Retroviral Syndrome
  3. Immunizations
    1. See Immunization in HIV
    2. General
      1. Do not give Live Vaccines (e.g. oral polio, Varicella Vaccine, Flumist) if CD4 Count <200
      2. Defer non-urgent Vaccinations until after Antiretroviral therapy initiated to boost immune response
    3. Specific Vaccinations
      1. Pneumococcal Vaccines
        1. Pneumococcal Conjugate Vaccine (e.g. PCV21)
        2. Try to give Pneumococcal Vaccines when CD4 Count >200
      2. Meningococcal Vaccine
        1. Give Quadrivalent Meningococcal Conjugate Vaccine (Menactra, Menveo)
        2. Repeat Meningococcal Vaccine every 5 years
      3. Covid-19 Vaccines
        1. However, immune response to Vaccine may be blunted
      4. Hepatitis B Vaccine (if HBsAg negative)
      5. Hepatitis A Vaccine (all of those susceptible)
      6. Influenza Vaccine annually
      7. Routine Tetanus Vaccine (Tdap or Td)
      8. Consider Hib Vaccine
      9. Human PapillomavirusVaccine (consider for those up to age 45 years old)
      10. Recombinant Herpes Zoster Vaccine (Shingrix, for those over age 50 years)
  4. Health Maintenance
    1. Routine preventive care as indicated (e.g. Pap Smear, Mammogram, skin exam, Colonoscopy)
    2. Manage comorbidities including Cardiovascular Risk Factors

XV. References

  1. Chu (2010) Am Fam Physician 81(10): 1239-44 [PubMed]
  2. Daar (2008) Curr Opin Hiv AIDS 3(1): 10-5 [PubMed]
  3. Daar (2001) Ann Intern Med 134:25-9 [PubMed]
  4. GoldSchmidt (2021) Am Fam Physician 103(7): 407-16 [PubMed]
  5. Khalsa (2006) Am Fam Physician 73:271-80 [PubMed]
  6. Niu (1993) J Infect Dis 168:1490-501 [PubMed]
  7. Perlmutter (1999) Am Fam Physician 60(2):535-542 [PubMed]

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