Resident Editor: Emma Bainbridge, MD

Faculty Editor: Brent Kobashi, MD 

Background

• Acute HIV infection is the time from HIV transmission until seroconversion (the development of antibodies against the virus), lasting 2-4 weeks in most individuals.
• Highest rates of transmission occur during acute HIV infection, likely due to high viremia (peaks between 2 weeks – 2 months), the characteristics of early viral variants, and the absence of neutralizing antibodies.
• MSM accounted for 67% of new HIV diagnoses in 2016. By race/ethnicity, African Americans and Hispanics/Latinos are disproportionally affected. 
• Treatment as prevention: early detection and treatment of acute HIV helps prevent transmission on the population level. 

Signs and Symptoms

• 50-90% of patients with acute HIV develop symptoms, usually within 2-4 weeks of transmission, and persisting for 2-4 weeks. In very unusual cases, symptoms of acute HIV can start months after transmission and be very prolonged.
• Symptomatic patients commonly present with:
  • Symptoms: fatigue (>70%), pharyngitis (>40%), arthralgias (>30%), myalgias (>40%), diarrhea (>30%), anorexia (>30%), night sweats (50%)
  • Signs: fever >38.5° Celsius  (>70%); lymphadenopathy (>40%); rash (>40%); oral or genital ulcers (20%), meningeal signs, oral thrush
• Rash commonly appears as red or pink maculopapular lesions distributed over the upper thorax, neck, face, and occasionally, extremities.
• May rarely present with neurological manifestations, including aseptic meningitis or encephalitis, Bell’s palsy, or radiculopathy.
• The initial drop in CD4 count rarely may be profound enough that patients present with opportunistic infections such as oral candidiasis, severe CMV infection, or pneumonia, including PCP.
• Severe symptoms and prolonged duration >14 days are associated with worse prognosis and more rapid progression to AIDS

Differential diagnosis

• Most easily confused with viral illnesses such as EBV, influenza and other viral URIs. 
• A positive heterophile agglutination test does not exclude a diagnosis of acute HIV.

Differential diagnosis of acute HIV symptoms

Evaluation

• HIV viral load is the earliest diagnostic test to turn positive (i.e. 10-15 days after transmission) and should always be ordered if acute HIV is suspected. A positive viral load in the context of a negative antibody test strongly suggests acute HIV. 
• Sensitivity and specificity of current PCR-based assays are 100% and >97%, respectively, prior to seroconversion. Note, viral load testing is expensive and is not always covered by insurance.  
• All of the latest versions of screening and confirmatory tests (rapid test, third and fourth generation enzyme immunoassays, Western blot) have >99% sensitivity and specificity after seroconversion.
• False positive HIV viral load testing is possible, especially in low prevalence settings, and should be suspected with low viral load results.
• UCSF currently offers fourth generation HIV antigen/antibody testing, which allows detection of HIV as soon as 15-20 days after transmission, compared to HIV antibody testing alone as HIV p24 antigen can be present prior to seroconversion. 
• Always screen for other STIs (chlamydia, gonorrhea, syphilis) and hepatitis B and C with a new HIV diagnosis. GC/CT testing should be offered for all sites where there may have been exposure (urine/cervical, throat, rectal). 
• If there is high clinical suspicion after a very recent high-risk exposure and both viral load and HIV screening test are negative, repeat the tests in 1-2 weeks

Treatment

• ART is recommended for all individuals with HIV, regardless of CD4 count and should be considered immediately after diagnosis. Initiation of therapy should be performed either by an HIV Specialist or with close consultation with an HIV specialist. 
• Given the increasing rates of primary resistance, it is recommended that providers follow their institution’s guidelines regarding HIV genotyping at the time of diagnosis. At many institutions, HIV genotype testing at the time of diagnosis (prior to the initiation of therapy) is considered the standard of care.
• Both the 2012 Recommendations of the International Antiviral Society-USA Panel and the US Dept. of Health and Human Services 2014  updated guidelines for antiretroviral therapy recommend offering treatment for acute HIV. Potential benefits are theoretical but include the following:
  • Decreased progression
  • Decrease severity of acute disease
  • Reduce size of viral reservoir
  • Preserving immune function by decreasing rate of viral mutation
• Clinical judgment should be exercised when initiating ART during acute HIV in non-adherent patients, as it may lead to earlier onset of drug resistance and limit their future treatment options.   
• All patients should have extensive risk reduction counseling to prevent further transmission.
• Diagnostic testing should also be performed on all recent sexual partners.

References

Chu C, Selwyn PA. Diagnosis and initial management of acute HIV infection. Am Fam Physician. 2010 May 15;81(10):1239-44

Cohen MS, Gay CL, Busch MP, Hecht FM. The detection of acute HIV infection. J Infect Dis. 2010 Oct 15;202 Suppl 2:S270-7

Cohen MS, Shaw GM, McMichael AJ, Haynes BF. (2011). Acute HIV-1 infection. N Engl J Med. 2011 May 19;364(20):1943-54

Kuhar DT, Henderson DK, Struble KA, et al. Updated US Public Health Service Guidelines for the Management of Occupational Exposures to Human Immunodeficiency Virus and Recommendations for Postexposure Prophylaxis. Infection Control and Hospital Epidemiology. 2013;34(9): 875-892

O'Brien M, & Markowitz M. Should we treat acute HIV infection? Curr HIV/AIDS Rep. 2012 Jun;9(2):101-10

Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA. 2012 Jul 25;308(4):387-402

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed 8/24/2014

Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58:e1-34.

Centers for Disease Control and Prevention. HIV in the United States: At A Glance. Updated 11/29/2017. https://www.cdc.gov/hiv/statistics/overview/ataglance.html. Accessed 03/27/2018.

Hecht FM, Busch MP, Rawal B, et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS. 2002;16(8):1119. 

Kinney RG and Wood BR. Basic HIV Primary Care. National HIV Curriculum. Available at: https://www.hiv.uw.edu/go/basic-primary-care/staging-initial-evaluation-monitoring/core-concept/all#staging-classifying-patients-hiv-disease. Accessed 03/27/2018.

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. Baseline evaluation. May 1, 2014.

Selik RM, Mokotoff ED, Branson B, et al. Revised Surveillance Case Definition for HIV Infection — United States, 2014. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention. 2014 Apr 11;63(RR-03):1-10.