Acute Retroviral Syndrome In The ED

Author: Charlie Caffrey, MD (EM Resident Physician, PGY-2, NUEM) // Edited by: Colin McCloskey, MD (EM Resident Physician, PGY-4, NUEM) // Expert Reviewer: Michael Angarone, DO

Citation: [Peer-Reviewed, Web Publication] Caffrey C, McCloskey C (2016, April 5). Acute Retroviral Syndrome In The ED. [NUEM Blog. Expert Peer Review by Angarone M]. Retrieved from


HIV testing does not get a lot of love in your average emergency department. Since 2006, the CDC has recommended HIV screening in all adult patients in high prevalence areas, ditching lengthy “opt-in” style consenting and counseling in the process [1]. However, despite these clear consensus recommendations, we are bad at them. Surveys have shown that in areas of relatively high HIV prevalence, less than 10% of hospitals report complying with screening guidelines [2].

This post is not to rail against the missed opportunity of failing to implement widespread routine HIV testing or the innumerable stresses that make such compliance impossible for many departments. Rather, it is to focus on the recognition and diagnosis of acute retroviral syndrome, an area in which we as diagnosticians can have a tremendous benefit.

Acute Retroviral Syndrome


What is acute retroviral syndrome? [3] 

  • A febrile, mononucleosis-like illness that 25-90% of the newly HIV infected patients will manifest
  • Occurs around 2-6 weeks after transmission
  • Characterized by fever, generalized lymphadenopathy, pharyngitis, night sweats, headache, nausea, and other symptoms
  • May last days or weeks
  • Extremely high viral levels, temporarily low CD4 cell counts
  • Virus infects wide variety of tissues, seeds the lymphoid organs

Why worry about acute retroviral HIV infection?

Consider acute retroviral syndrome like endocarditis or meningitis or epidural abscess: another life threatening cause of a seemingly benign febrile illness that we must recognize. HIV infection, especially in its primary phase, represents a life threatening malady that could have serious implications on the patient and the public health at large if not diagnosed.

Consider this:

  • Extremely high viral levels means extreme infectivity during this time: Some studies indicate that the acute phase accounts for up to 50% of transmission of the disease [4].
  • Informing people of their status reduces high risk behavior [5]. Catching the virus early might have enormous public health benefits.
  • Emerging evidence that treating with HAART during primary HIV prolongs the time until development of AIDS and reduces transmission of the virus [6].
  • You may have seen febrile patients that have actually had acute retroviral syndrome. One study which retrospectively tested blood samples sent for heterophile screening showed test results consistent with acute HIV infection in 1.2% of samples [7].

High risk historical features in your febrile patient:

  • High risk sexual activity (ask about in recent weeks!)
  • IV drug use
  • Men who have sex with men
  • Sex workers
  • HIV endemicity in your area
  • Positive for other STDs

High risk symptoms:

  • Genital ulcers
  • Weight loss
  • Vomiting
  • Swollen lymph nodes
  • Fever

Other symptoms may include:

  • Pharyngitis
  • Arthralgias
  • Diarrhea
  • Fatigue
  • Night sweats
  • Headaches
  • Genital warts
  • Rashes

High risk physical exam findings:

  • Any lymphadenopathy - highest sensitivity for primary HIV

  • Genital ulcers

  • Rash

  • Genital warts

Lymphadenopathy can be difficult to appreciate. In one study series only 17% of primary care providers accurately recognized prominent diffuse lymphadenopathy [8]. Stanford 25 has some useful tips on this under-appreciated exam technique

Fourth Generation HIV Testing in the Emergency Department

Today’s fourth generation HIV tests detect not only HIV antibodies but also HIV p24 antigens. Testing for the p24 antigen has allowed for detection of primary HIV infections which may have escaped earlier antibody-only testing methods, before the body can mount a detectable immune response. One study of an opt-in HIV screening program using a fourth generation antigen/antibody test revealed close to 25% of the newly diagnosed HIV infections were acute phase infections [9]. However, there will still be a period of time in which the infection may only be confirmed by presence of HIV RNA, via time and cost-intensive nucleic acid amplification testing.

Testing Approaches

The first approach that emergency departments should adopt is “opt-out” style general HIV screening using a fourth generation antibody/antigen test of all adult patients. Such an approach would be successful in identifying many cases of acute primary HIV, beyond those that are openly symptomatic. In many overburdened emergency departments, this approach for the time being may prove unrealistic, barring major investments in the public health.

A second approach: send an HIV fourth generation assay on all of your febrile patients with high risk symptoms and risk factors. In patients with negative HIV Ab/Ag tests but especially high pretest probability (genital sores, febrile, lymphadenopathy), consider sending an HIV RNA PCR, or arranging for close follow-up for repeat HIV Ab/Ag testing, and inform the patient of your concern in order to cut down on high risk behaviors.

It is important to note that an HIV RNA PCR takes several hours, longer than the typical ED stay.  If they aren’t admitted, they will need to return to receive a positive test, or however your department handles your HIV tests that result after the patient leaves.

Final Thoughts

  • Question all your febrile patients about HIV risk factors! Acute retroviral syndrome is worth considering in all patients with fever.
  • Recognition and early diagnosis of primary HIV has numerous public health benefits
  • Help diagnose primary HIV, either by:
    • Instituting CDC-recommended HIV Ab/Ag screening for all ED adult patients, with targeted HIV RNA PCR sent on high risk patients with symptoms of acute retroviral syndrome.
    • Sending fourth generation HIV Ab/Ag testing of all febrile patients with risk factors. If negative but still high risk or high risk historical factors, send an HIV RNA PCR or arrange outpatient follow-up for further testing.

Expert Commentary


Thank you for this excellent post on acute retroviral syndrome in individuals acutely infected with HIV.

Recognition of this syndrome is just as important for emergency medicine physicians as primary care providers. Many patients with acute HIV infection will be asymptomatic, but in those that develop symptoms the diagnosis of HIV infection is often overlooked due to the lack of specificity of the symptoms.  Fever, fatigue, myalgias, lymphadenopathy, sore throat and rash are the primary symptoms of acute HIV infection. These symptoms are seen in wide variety of infectious and non-infectious conditions (e.g. EBV and CMV mononucleosis, syphilis, viral hepatitis or SLE) that may be more common than HIV infection. 

Considering how non-specific the clinical syndrome of acute-HIV infection is, clinicians should consider the diagnosis of acute HIV in any patient presenting with the “retroviral syndrome” or any other ill-defined febrile syndrome.

There is overwhelming benefit to diagnosis of HIV in the acute or early stage. Patients with acute infection have very high serum viral loads and are very likely to transmit the virus. Awareness of an individual’s HIV status can help to alter sexual habits which in turn can reduce transmission. One of the most important points to early diagnosis is early treatment for HIV infection [10]. Numerous studies have shown that earlier treatment allows for preservation of the immune system and CD4 T-lymphocytes, which is associated with decreased mortality. The Strategies for Management of Antiretroviral Therapy (SMART) study looked at individuals treated for HIV early versus delayed (treatment beginning once CD4 <250 cells). In this study the risk of death or development of AIDS was much higher in the delayed therapy group with a hazard ratio 5.3 (1.3-9.6) [11].

The major issue for emergency room physicians is what to do with the results of a positive HIV test or "how do I get the patient follow-up in a clinic?" 

The best way to deal with these issues is to establish communication with HIV specialists or a primary care team working at the hospital that can provide further counseling and follow up for those individuals that test positive or who are at high risk for HIV infection. Here at Northwestern there is a pager, HIV Rapid Diagnosis Pager, which is covered by an HIV specialist or our HIV nurse practitioner.  We are accessible 24-hours a day to help with counseling or to establish follow-up for any patient diagnosed with HIV infection.

The diagnosis of acute HIV infection (the “retroviral syndrome”) requires a high-index of suspicion and recognition being that this syndrome is non-specific and encompasses many other diseases, infectious and non-infectious.

Diagnosis is important secondary to the effects on public health and spread of HIV infection, but more importantly on the impact for the individual infected with HIV. Diagnosis of HIV infection gets the patient into care, gets the patient on treatment and offers improved long term outcomes. At Northwestern the ED staff can contact an HIV specialist to help with any questions that may arise regarding testing, counseling or follow-up.


Michael Angarone, DO

Assistant Professor; Division of Infectious Diseases; Northwestern University Feinberg School of Medicine


  1. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006 Sep 22;55(RR-14):1-17; quiz CE1-4.
  2. Herrin J, Wesolowski LG, Heffelfinger JD, et al. HIV screening practices and hospital characteristics in the US, 2009-2010. Public Health Rep. 2013 May-Jun;128(3):161-9.
  3. Cooper DA, Gold J, Maclean P, et al. Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion. Lancet. 1985 Mar 9;1(8428):537-40.
  4. Brenner BG, Roger M, Routy JP, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis. 2007 Apr 1;195(7):951-9.
  5. Weinhardt LS, Carey MP, Johnson BT, Bickham NL. Effects of HIV counseling and testing on sexual risk behavior: a meta-analytic review of published research, 1985-1997. Am J Public Health. 1999 Sep;89(9):1397-405.
  6. O'Brien M, Markowitz M. Should we treat acute HIV infection? Curr HIV/AIDS Rep. 2012 Jun;9(2):101-10.
  7. Rosenberg ES, Caliendo AM, Walker BD. Acute HIV infection among patients tested for mononucleosis. N Engl J Med. 1999 Mar 25;340(12):969.
  8. Wood E, Kerr T, Rowell G, et al. Does this adult patient have early HIV infection?: The Rational Clinical Examination systematic review. JAMA. 2014 Jul 16;312(3):278-85.
  9. Geren KI, Lovecchio F, Knight J, et al. Identification of acute HIV infection using fourth-generation testing in an opt-out emergency department screening program. Annals of emergency medicine. 2014 Nov;64(5):537-46.
  10. Marks G, Crepaz N, Senterfitt JW, Janssen RS. Meta-analysis of high-risk sexual behavior in persons aware and unaware they are infected with HIV in the United States: implications for HIV prevention programs. J Acquir Immune Defic Syndr. 2005 Aug 1;39(4):446-53.
  11. Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, Gatell JM, Girard PM,Grund B, Law M, Losso MH, Palfreeman A, Wood R. Major clinical outcomes in antiretroviral therapy (ART)-naïve participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008 Apr 15;197(8):1133-44