Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Acute and early HIV infection: Clinical manifestations and diagnosis

Paul E Sax, MD
Section Editor
John G Bartlett, MD
Deputy Editor
Allyson Bloom, MD


Acute HIV infection may present as a mononucleosis type of syndrome with a constellation of nonspecific symptoms. Without a high degree of suspicion, the diagnosis can frequently be missed by clinicians. In some cases, early HIV infection may be asymptomatic.

The clinical manifestations and diagnosis of acute and early HIV will be reviewed here. The pathogenesis, epidemiology, and treatment of early HIV infection are discussed separately. (See "Acute and early HIV infection: Pathogenesis and epidemiology" and "Acute and early HIV infection: Treatment".)


Different terms, including acute, recent, primary, and early HIV infection, have been used in the literature to refer to variable intervals following initial infection with the virus. In this topic, we use the term "early HIV infection" to refer to the approximate six-month period following HIV acquisition. We use the term "acute HIV infection" to refer to symptomatic early infection, as this reflects common usage in clinical care.


Asymptomatic infection — An estimated 10 to 60 percent of individuals with early HIV infection will not experience symptoms [1], although the exact proportion is difficult to estimate since patients generally come to attention because of symptoms, and thus asymptomatic infections often remain undetected. In a study of 50 acutely infected individuals who had been identified by prospective viral testing of high-risk individuals and then were followed twice weekly, almost all had at least one reported symptom or sign during the first four weeks of infection, but these were mainly short-lived, nonspecific, and unlikely to have brought the individual to clinical attention outside of a study setting [2]. Subjects complained of symptoms at only 29 percent of the biweekly study visits during this period.

Time course — In patients who have acute symptomatic infection, the usual time from HIV exposure to the development of symptoms is two to four weeks, although incubation periods as long as ten months have been observed [3]. In one study that evaluated viral dynamics following HIV infection, the highest frequency of symptoms and signs were observed just before peak viremia occurred, approximately two weeks after the initial detection of viral RNA [2]. It is possible that the route of acquisition and quantity of virus inoculum influence the time to peak viremia and the length of the incubation period.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: May 25, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. 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/lvguidelines/AdultandAdolescentGL.pdf (Accessed on May 01, 2014).
  2. Robb ML, Eller LA, Kibuuka H, et al. Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand. N Engl J Med 2016; 374:2120.
  3. Ridzon R, Gallagher K, Ciesielski C, et al. Simultaneous transmission of human immunodeficiency virus and hepatitis C virus from a needle-stick injury. N Engl J Med 1997; 336:919.
  4. Kared H, Lelièvre JD, Donkova-Petrini V, et al. HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection. AIDS 2008; 22:2451.
  5. Niu MT, Stein DS, Schnittman SM. Primary human immunodeficiency virus type 1 infection: review of pathogenesis and early treatment intervention in humans and animal retrovirus infections. J Infect Dis 1993; 168:1490.
  6. Daar ES, Little S, Pitt J, et al. Diagnosis of primary HIV-1 infection. Los Angeles County Primary HIV Infection Recruitment Network. Ann Intern Med 2001; 134:25.
  7. Braun DL, Kouyos RD, Balmer B, et al. Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1 Infection. Clin Infect Dis 2015; 61:1013.
  8. Daar ES, Pilcher CD, Hecht FM. Clinical presentation and diagnosis of primary HIV-1 infection. Curr Opin HIV AIDS 2008; 3:10.
  9. Kelley CF, Barbour JD, Hecht FM. The relation between symptoms, viral load, and viral load set point in primary HIV infection. J Acquir Immune Defic Syndr 2007; 45:445.
  10. Lavreys L, Baeten JM, Chohan V, et al. Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women. Clin Infect Dis 2006; 42:1333.
  11. McKellar MS, Cope AB, Gay CL, et al. Acute HIV-1 infection in the Southeastern United States: a cohort study. AIDS Res Hum Retroviruses 2013; 29:121.
  12. Quinn TC. Acute primary HIV infection. JAMA 1997; 278:58.
  13. Pedersen C, Lindhardt BO, Jensen BL, et al. Clinical course of primary HIV infection: consequences for subsequent course of infection. BMJ 1989; 299:154.
  14. Gaines H, von Sydow M, Pehrson PO, Lundbegh P. Clinical picture of primary HIV infection presenting as a glandular-fever-like illness. BMJ 1988; 297:1363.
  15. Schacker T, Collier AC, Hughes J, et al. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med 1996; 125:257.
  16. Tindall B, Cooper DA. Primary HIV infection: host responses and intervention strategies. AIDS 1991; 5:1.
  17. Valle SL. Febrile pharyngitis as the primary sign of HIV infection in a cluster of cases linked by sexual contact. Scand J Infect Dis 1987; 19:13.
  18. de Jong MD, Hulsebosch HJ, Lange JM. Clinical, virological and immunological features of primary HIV-1 infection. Genitourin Med 1991; 67:367.
  19. Lapins J, Gaines H, Lindbäck S, et al. Skin and mucosal characteristics of symptomatic primary HIV-1 infection. AIDS Patient Care STDS 1997; 11:67.
  20. Stamm WE, Handsfield HH, Rompalo AM, et al. The association between genital ulcer disease and acquisition of HIV infection in homosexual men. JAMA 1988; 260:1429.
  21. Rabeneck L, Popovic M, Gartner S, et al. Acute HIV infection presenting with painful swallowing and esophageal ulcers. JAMA 1990; 263:2318.
  22. Calabrese LH, Proffitt MR, Levin KH, et al. Acute infection with the human immunodeficiency virus (HIV) associated with acute brachial neuritis and exanthematous rash. Ann Intern Med 1987; 107:849.
  23. Rizzardi GP, Tambussi G, Lazzarin A. Acute pancreatitis during primary HIV-1 infection. N Engl J Med 1997; 336:1836.
  24. Molina JM, Welker Y, Ferchal F, et al. Hepatitis associated with primary HIV infection. Gastroenterology 1992; 102:739.
  25. Meersseman W, Van Laethem K, Lagrou K, et al. Fatal brain necrosis in primary HIV infection. Lancet 2005; 366:866.
  26. Ho DD, Sarngadharan MG, Resnick L, et al. Primary human T-lymphotropic virus type III infection. Ann Intern Med 1985; 103:880.
  27. Ho DD, Rota TR, Schooley RT, et al. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 1985; 313:1493.
  28. Carne CA, Tedder RS, Smith A, et al. Acute encephalopathy coincident with seroconversion for anti-HTLV-III. Lancet 1985; 2:1206.
  29. Denning DW, Anderson J, Rudge P, Smith H. Acute myelopathy associated with primary infection with human immunodeficiency virus. Br Med J (Clin Res Ed) 1987; 294:143.
  30. Hagberg L, Malmvall BE, Svennerholm L, et al. Guillain-Barré syndrome as an early manifestation of HIV central nervous system infection. Scand J Infect Dis 1986; 18:591.
  31. Parry GJ. Peripheral neuropathies associated with human immunodeficiency virus infection. Ann Neurol 1988; 23 Suppl:S49.
  32. Piette AM, Tusseau F, Vignon D, et al. Acute neuropathy coincident with seroconversion for anti-LAV/HTLV-III. Lancet 1986; 1:852.
  33. Ong EL, Mandal BK. Primary HIV-I infection associated with pneumonitis. Postgrad Med J 1991; 67:579.
  34. Longworth DL, Spech TJ, Ahmad M, et al. Lymphocytic alveolitis in primary HIV infection. Cleve Clin J Med 1990; 57:379.
  35. Mahé A, Bruet A, Chabin E, Fendler JP. Acute rhabdomyolysis coincident with primary HIV-1 infection. Lancet 1989; 2:1454.
  36. Bernard E, Dellamonica P, Michiels JF, et al. Heparine-like anticoagulant vasculitis associated with severe primary infection by HIV. AIDS 1990; 4:932.
  37. Gupta KK. Acute immunosuppression with HIV seroconversion. N Engl J Med 1993; 328:288.
  38. Cilla G, Perez Trallero E, Furundarena JR, et al. Esophageal candidiasis and immunodeficiency associated with acute HIV infection. AIDS 1988; 2:399.
  39. Isaksson B, Albert J, Chiodi F, et al. AIDS two months after primary human immunodeficiency virus infection. J Infect Dis 1988; 158:866.
  40. Tindall B, Hing M, Edwards P, et al. Severe clinical manifestations of primary HIV infection. AIDS 1989; 3:747.
  41. Vento S, Di Perri G, Garofano T, et al. Pneumocystis carinii pneumonia during primary HIV-1 infection. Lancet 1993; 342:24.
  42. Moss PJ, Read RC, Kudesia G, McKendrick MW. Prolonged cryptosporidiosis during primary HIV infection. J Infect 1995; 30:51.
  43. Cooper DA, Tindall B, Wilson EJ, et al. Characterization of T lymphocyte responses during primary infection with human immunodeficiency virus. J Infect Dis 1988; 157:889.
  44. Vidrih JA, Walensky RP, Sax PE, Freedberg KA. Positive Epstein-Barr virus heterophile antibody tests in patients with primary human immunodeficiency virus infection. Am J Med 2001; 111:192.
  45. Colven R, Harrington RD, Spach DH, et al. Retroviral rebound syndrome after cessation of suppressive antiretroviral therapy in three patients with chronic HIV infection. Ann Intern Med 2000; 133:430.
  46. Kilby JM, Goepfert PA, Miller AP, et al. Recurrence of the acute HIV syndrome after interruption of antiretroviral therapy in a patient with chronic HIV infection: A case report. Ann Intern Med 2000; 133:435.
  47. Daar ES, Bai J, Hausner MA, et al. Acute HIV syndrome after discontinuation of antiretroviral therapy in a patient treated before seroconversion. Ann Intern Med 1998; 128:827.
  48. http://www.cdc.gov/hiv/pdf/HIVtestingAlgorithmRecommendation-Final.pdf (Accessed on June 30, 2014).
  49. Centers for Disease Control and Prevention (CDC). Detection of acute HIV infection in two evaluations of a new HIV diagnostic testing algorithm - United States, 2011-2013. MMWR Morb Mortal Wkly Rep 2013; 62:489.
  50. Rich JD, Merriman NA, Mylonakis E, et al. Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case series. Ann Intern Med 1999; 130:37.
  51. Schwartz DH, Laeyendecker OB, Arango-Jaramillo S, et al. Extensive evaluation of a seronegative participant in an HIV-1 vaccine trial as a result of false-positive PCR. Lancet 1997; 350:256.
  52. Stekler J, Maenza J, Stevens CE, et al. Screening for acute HIV infection: lessons learned. Clin Infect Dis 2007; 44:459.
  53. Hecht FM, Busch MP, Rawal B, et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS 2002; 16:1119.
  54. Pilcher CD, Fiscus SA, Nguyen TQ, et al. Detection of acute infections during HIV testing in North Carolina. N Engl J Med 2005; 352:1873.
  55. Patel P, Mackellar D, Simmons P, et al. Detecting acute human immunodeficiency virus infection using 3 different screening immunoassays and nucleic acid amplification testing for human immunodeficiency virus RNA, 2006-2008. Arch Intern Med 2010; 170:66.
  56. Cohen MS, Gay CL, Busch MP, Hecht FM. The detection of acute HIV infection. J Infect Dis 2010; 202 Suppl 2:S270.
  57. Fiebig EW, Wright DJ, Rawal BD, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 2003; 17:1871.
  58. Pandori MW, Hackett J Jr, Louie B, et al. Assessment of the ability of a fourth-generation immunoassay for human immunodeficiency virus (HIV) antibody and p24 antigen to detect both acute and recent HIV infections in a high-risk setting. J Clin Microbiol 2009; 47:2639.
  59. Chavez P, Wesolowski L, Patel P, et al. Evaluation of the performance of the Abbott ARCHITECT HIV Ag/Ab Combo Assay. J Clin Virol 2011; 52 Suppl 1:S51.
  60. Owen SM. Testing for acute HIV infection: implications for treatment as prevention. Curr Opin HIV AIDS 2012; 7:125.
  61. Branson BM, Stekler JD. Detection of acute HIV infection: we can't close the window. J Infect Dis 2012; 205:521.
  62. De Souza MS, Phanuphak N, Pinyakorn S, et al. Impact of nucleic acid testing relative to antigen/antibody combination immunoassay on the detection of acute HIV infection. AIDS 2015; 29:793.
  63. Peters PJ, Westheimer E, Cohen S, et al. Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population. JAMA 2016; 315:682.
  64. Rosenberg NE, Kamanga G, Phiri S, et al. Detection of acute HIV infection: a field evaluation of the determine® HIV-1/2 Ag/Ab combo test. J Infect Dis 2012; 205:528.
  65. Kassutto S, Johnston MN, Rosenberg ES. Incomplete HIV type 1 antibody evolution and seroreversion in acutely infected individuals treated with early antiretroviral therapy. Clin Infect Dis 2005; 40:868.
  66. Hare CB, Pappalardo BL, Busch MP, et al. Seroreversion in subjects receiving antiretroviral therapy during acute/early HIV infection. Clin Infect Dis 2006; 42:700.
  67. Selleri M, Orchi N, Zaniratti MS, et al. Effective highly active antiretroviral therapy in patients with primary HIV-1 infection prevents the evolution of the avidity of HIV-1-specific antibodies. J Acquir Immune Defic Syndr 2007; 46:145.
  68. Connick E. Incomplete antibody evolution and seroreversion after treatment of primary HIV type 1 infection: what is the clinical significance? Clin Infect Dis 2005; 40:874.
  69. Kothe D, Byers RH, Caudill SP, et al. Performance characteristics of a new less sensitive HIV-1 enzyme immunoassay for use in estimating HIV seroincidence. J Acquir Immune Defic Syndr 2003; 33:625.
  70. Hirsch MS, Günthard HF, Schapiro JM, et al. Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Clin Infect Dis 2008; 47:266.
  71. Yanik EL, Napravnik S, Hurt CB, et al. Prevalence of transmitted antiretroviral drug resistance differs between acutely and chronically HIV-infected patients. J Acquir Immune Defic Syndr 2012; 61:258.
  72. Jain V, Liegler T, Vittinghoff E, et al. Transmitted drug resistance in persons with acute/early HIV-1 in San Francisco, 2002-2009. PLoS One 2010; 5:e15510.
  73. Hurt CB, McCoy SI, Kuruc J, et al. Transmitted antiretroviral drug resistance among acute and recent HIV infections in North Carolina from 1998 to 2007. Antivir Ther 2009; 14:673.
  74. Smith DM, Wong JK, Shao H, et al. Long-term persistence of transmitted HIV drug resistance in male genital tract secretions: implications for secondary transmission. J Infect Dis 2007; 196:356.
  75. Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med 1991; 324:961.
  76. Celum CL, Robinson NJ, Cohen MS. Potential effect of HIV type 1 antiretroviral and herpes simplex virus type 2 antiviral therapy on transmission and acquisition of HIV type 1 infection. J Infect Dis 2005; 191 Suppl 1:S107.
  77. Colfax GN, Buchbinder SP, Cornelisse PG, et al. Sexual risk behaviors and implications for secondary HIV transmission during and after HIV seroconversion. AIDS 2002; 16:1529.
  78. Hollingsworth TD, Pilcher CD, Hecht FM, et al. High Transmissibility During Early HIV Infection Among Men Who Have Sex With Men-San Francisco, California. J Infect Dis 2015; 211:1757.
  79. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005; 191:1403.
  80. Brenner BG, Roger M, Routy JP, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 2007; 195:951.
  81. O'Brien M, Markowitz M. Should we treat acute HIV infection? Curr HIV/AIDS Rep 2012; 9:101.
  82. Patterson KB, Leone PA, Fiscus SA, et al. Frequent detection of acute HIV infection in pregnant women. AIDS 2007; 21:2303.