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Acute human immunodeficiency virus infection syndrome

Author: Made Ananda Krisna, General practitioner Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas, Indonesia; Chief Editor: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. September 2015.


What is acute human immunodeficiency virus infection syndrome?

Acute human immunodeficiency virus infection syndrome refers to symptoms experienced by many people at the time of initial infection with human immunodeficiency virus (HIV). It is also known as acute retroviral syndrome.

The syndrome consists of nonspecific symptoms including fever and rash. It resolves gradually as seroconversion occurs.1,2

Who gets acute HIV infection syndrome?

It is estimated that acute HIV infection syndrome occurs in 40 to 90% of people infected with HIV during the first few weeks after initial exposure.3

HIV infection occurs predominately through sexual exposure in most areas of the world. There are some geographical areas where intravenous transmission among intravenous drug users or via nosocomial transmission also occur. Mother to child transmission is becoming less frequent as a result of HIV testing and treatment during pregnancy.

What causes acute HIV infection syndrome?

HIV belongs to the Retroviridae family of viruses. There are two subgroups: HIV-1 and HIV 2.

  • HIV-1 infection causes most cases worldwide
  • HIV-2 infection cases are infrequent with nearly all cases arising in West Africa

Symptoms begin after the virus has successfully infected its specific target, T helper/CD4 cells, followed by bursting viraemia.1 A very high viral load incites cytokine production by the innate immune system causing the clinical syndrome.2

What are the clinical features of acute HIV infection syndrome?

Acute HIV infection syndrome is classified according to general, neurologic, and dermatological manifestations.1 Fever is the most common symptom. None of the symptoms or signs of acute HIV infection syndrome are specific to acute HIV infection. 4–7 However, they are very infectious at this time due to the high HIV viral load. Early diagnosis is important to prevent sexual transmission during the highly viraemic phase of acute HIV infection.

General symptoms

  • Fever
  • Sore throat
  • Swollen lymph nodes
  • Headache/pain behind the eyes
  • Sore muscles and joints
  • Malaise
  • Loss of appetite, with or without weight loss
  • Gastrointestinal tract symptoms: nausea, vomiting, diarrhoea

Neurological symptoms

  • Meningitis
  • Encephalitis
  • Peripheral neuropathy
  • Myelopathy

Dermatological symptoms

  • Erythematous maculopapular rash
  • Mucocutaneous ulceration

The rash is a symmetrical maculopapular erythematous exanthem that involves face, palms and soles as well as trunk and limbs.

About 10% of cases of acute HIV infection syndrome are atypical and present with fulminant immunological and clinical collapse, sometimes with an opportunistic infection.1

How is acute HIV infection syndrome diagnosed?

Diagnosis depends on observing typical clinical features together with evidence of HIV infection.8 The currently favoured algorithm combines an antigen and antbody i.e. the HIV (1+2) Ag/Ab test and/or an HIV RNA test.

  • The antigen component of the combined test is reactive 15 to 20 days after exposure.
  • An HIV RNA test may be reactive as early as 10 to 15 days after exposure.

Once HIV infection has been confirmed, further tests are performed to clarify immune function and background HIV resistance before starting treatment.

  • HIV viral load
  • HIV anti-retroviral resistance and genotyping
  • CD4 T lymphocyte count

Western blot testing is no longer performed by many laboratories.

HIV viral load levels are high at the time of HIV seroconversion. The HIV viral load reaches a "set point" once specific cytotoxic T cells begin to fight the virus. A high set point means a high viral load and expectation of rapid progression of disease. A lower set point and lower viral load in general predicts slower progression.

What is the treatment for acute HIV infection syndrome?

Recommendations to treat or not to treat acute HIV infection have altered in recent years. In 2015, most experts recommend commencing antiretroviral treatment (ART) as soon as the diagnosis of HIV infection is made and the patient has a good understanding of the importance of adherence to treatment. The benefits of early treatment have been supported by a randomised clinical trial (START study, 2015).9

The aim of ART is to suppress HIV RNA count to undetectable levels. Genotypic antiretroviral (ARV) drug resistance testing helps in the selection of an effective regimen of several active medications. Not all drugs are available or funded in every country.

HIV treatments are continuing to evolve. A comprehensive view on what regimen should be commenced is beyond the scope of this article. A good resource on treatment is available at the DHHS website AIDSinfo.

What is the outcome for acute HIV infection syndrome?

The symptoms of acute HIV infection syndrome settle within a few days to weeks.

Once HIV infection is established, there is a clinical latency period when patients may be asymptomatic. The median time of this period is approximately 10 years, during which there is active HIV replication and CD4 T-cell count declines.

Chronic HIV symptoms are variable, mostly depending on CD4 count and/or viral load. If HIV infection is not detected and treated with ART, progression to AIDS spectrum of illness is inevitable with opportunistic infections and/or malignancy.



  1. Fauci AS, Lane HC. Human immunodeficiency virus disease: AIDS and related disorders. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Localzo J. Harrison’s principles of internal medicine. 18th ed. New York: McGraw-Hill; 2012. p. 1506-87.
  2. Stacey AR, Norris PJ, Qin L, et al. Induction of striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infection. J Virol. 2009; 83 (8): 3719-33. (Cited by: Cohen MS, Gay CL, Busch MP, Hecht FM. The detection of acute HIV infection. JID. 2010; 202: s270-7.)
  3. Schacker T, et al. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med. 1996; 125 (4): 257-64. (Cited by: Chu C, Selwyn PA. Diagnosis and initial management of acute HIV infection. Am Fam Physician. 2010; 81 (10): 1239-44.)
  4. Global report 2010. Geneva: UNAIDS, 2010.(Cited by: Cohen MS, Shaw GM, McMichael AJ, Haynes BF. Acute HIV-1 infection. N Engl J Med. 2011; 364 (20): 1943-54.)
  5. [Internet]. New Mexico: New Mexico AIDS Education and Training Center; c1998-2014 [updated 2014 June 4; cited 2015 August 30]. Available from:
  6. Sax PE [Internet]. Netherlands: Wolters Kluwer; c2015 [updated 2014 Jan 8; cited 2015 August 30]. Available from:
  7. Daar ES, Little S, Pitt J, et al. Diagnosis of primary HIV-1 infection. Loas Angeles Country HIV Infection Recruitment Network. Ann Intern Med. 2001; 134 (1): 25-9 (Cited by: Chu C, Selwyn PA. Diagnosis and initial management of acute HIV infection. Am Fam Physician. 2010; 81 (10): 1239-44.)
  8. Keele BF, Giorgi EE, Salazar-Gonzalez JF, et al. The first T cell response to transmitted/founder virus contributes to the control of acute virema in HIV-1 infection. J Exp Med. 2009; 206 (6): 1253-72. (Cited by: Cohen MS, Gay CL, Busch MP, Hecht FM. The detection of acute HIV infection. JID. 2010; 202: s270-7.)
  9. INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015 Aug 27;373(9):795-807. DOI: 10.1056/NEJMoa1506816. Epub 2015 Jul 20. PubMed PMID: 26192873; PubMed Central PMCID: PMC4569751. Journal.
  10. O'Brien M, Markowitz M. Should we treat acute HIV infection? Curr HIV/AIDS Rep. 2012 Jun;9(2):101-10. doi: 10.1007/s11904-012-0113-0. PMID: 22415472; PMCID: PMC3718035.
  11. DHHS 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: Accessed [2015 August 30]

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