AIDS: Clinical Manifestations


Human immunodeficiency virus (HIV) affects the host's immune system over time. As a result, HIV‐infected people can experience a wide range of clinical manifestations, especially if the infection is not treated with combination antiretroviral therapy (cART). In advanced stages of the disease, patients eventually risk severe illnesses. More than 20 conditions, including opportunistic infections and malignancies, have been classified as acquired immune deficiency syndrome (AIDS)‐defining illnesses. With the success of cART producing long‐term viral suppression and immune reconstitution, the major clinical complications of chronic infection now are serious non‐AIDS‐related events. This term refers to an increasing rate of cardiovascular, liver and renal diseases as well as neoplasms occurring in long‐term treated patients with longer life expectancies. However, there are still significant differences in access to and availability of antiretroviral therapy throughout the world which leads to contrasting patterns in the spectrum of AIDS‐defining illnesses in resource‐limited settings and developed countries.

Key Concepts:

  • AIDS arise from a compromised immune system and the resulting loss of host defences and immune surveillance mechanisms.

  • The spectrum of AIDS‐defining illnesses varies in developed and resource‐limited settings.

  • Pneumocystis jiroveci pneumonia is the most common AIDS‐related illness in developed countries.

  • Tuberculosis is the most common AIDS‐related illness in developing countries.

  • Many AIDS‐related infections represent recrudescence of latent infection rather than de novo acquisition.

  • Antiretroviral therapy has had a significant impact on the spectrum of ADIs.

  • AIDS‐related malignancies occur at increased rates in chronically infected patients and these tend to have a viral associated aetiology.

  • Effective antiretroviral therapy has resulted in prolonged suppression of viral replication, sustained immune reconstitution and very substantial reductions in AIDS‐related morbidity and mortality.

  • Owing to increases in life expectancy resulting from effective antiretroviral therapy serious non‐AIDS‐related illnesses have become more important in clinical management.

Keywords: HIV; AIDS; clinical spectrum; opportunistic infections; SNAEs; cancer

Figure 1.

CD4 range and AIDS clinical spectrum. List is indicative, not exhaustive. Adapted from Crowe SM, Carlin JB, Stewart KI, Lucas CR and Hoy JF (1991) Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV‐infected persons. Journal of Acquired Immune Deficiency Syndromes4(8): 770–776. © Lippincott Williams.



Ansari NA, Kombe AH, Kenyon TA et al. (2002) Pathology and causes of death in a group of 128 predominantly HIV‐positive patients in Botswana, 1997–1998. International Journal of Tuberculosis and Lung Disease 6: 55–63.

Barre‐Sinoussi F, Chermann JC, Rey F et al. (1983) Isolation of a T‐lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220: 868–871.

Carr A, Marriott D, Field A, Vasak E and Cooper DA (1998) Treatment of HIV‐1‐associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 351: 256–261.

CDC (1982) Update on acquired immune deficiency syndrome (AIDS) – United States. Morbidity and Mortality Weekly Report 31: 507–508, 513–514.

CDC (1985) Revision of the case definition of acquired immunodeficiency syndrome for national reporting – United States. Morbidity and Mortality Weekly Report 34: 373–375.

CDC (1987) Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases. Morbidity and Mortality Weekly Report 36(suppl. 1): 1S–15S.

CDC (1992) 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recommendations and Reports 41(RR‐17): 1–19.

CDC (1999) Guidelines for national human immunodeficiency virus case surveillance, including monitoring for human immunodeficiency virus infection and acquired immunodeficiency syndrome. Centers for Disease Control and Prevention. MMWR Recommendations and Reports 48: 1–27, 29–31.

CDC (2014) Revised surveillance case definition for HIV infection – United States. Centers for Disease Control and Prevention. Recommendations and Reports 63(RR03): 1–10.

Cesarman E (2013) Pathology of lymphoma in HIV. Current Opinion in Oncology 25(5): 487–494.

Chaturvedi AK, Madeleine MM, Biggar RJ and Engels EA (2009) Risk of human papillomavirus‐associated cancers among persons with AIDS. Journal of the National Cancer Institute 101: 1120–1130.

Chawla R and Ichhpujani RL (2011) Enteric spore‐forming opportunistic parasites in HIV/AIDS. Tropical Parasitology 1: 15–19.

Cohen MS, Chen YQ, McCauley M et al. (2011) Prevention of HIV‐1 infection with early antiretroviral therapy. New England Journal of Medicine 365: 493–505.

Cooper DA (2008) Life and death in the cART era. Lancet 372: 266–267.

Crum‐Cianflone N, Hullsiek KH, Marconi V et al. (2009) Trends in the incidence of cancers among HIV‐infected persons and the impact of antiretroviral therapy: a 20‐year cohort study. AIDS 23: 41–50.

Deeks SG, Lewin SR and Havlir DV (2013) The end of AIDS: HIV infection as a chronic disease. Lancet 382: 1525–1533.

Dore GJ, Li Y, McDonald A, Ree H and Kaldor JM (2002) Impact of highly active antiretroviral therapy on individual AIDS‐defining illness incidence and survival in Australia. Journal of Acquired Immune Deficiency Syndromes 29: 388–395.

Dore GJ, McDonald A, Li Y, Kaldor JM and Brew BJ (2003) Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 17(10): 1539–1545.

Ebrahim SH, Abdullah AS, McKenna M and Hamers FF (2004) AIDS‐defining cancers in Western Europe, 1994–2001. AIDS Patient Care and STDs 18: 501–508.

Gottlieb MS, Schroff R, Schanker HM et al. (1981) Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. New England Journal of Medicine 305: 1425–1431.

Grulich AE (2000) Update: cancer risk in persons with HIV/AIDS in the era of combination antiretroviral therapy. AIDS Reader Journal 10: 341–346.

Gullo FP, Rossi SA, Sardi Jde C et al. (2013) Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment. European Journal of Clinical Microbiology & Infectious Diseases 32: 1377–1391.

Harrison KM, Song R and Zhang X (2010) Life expectancy after HIV diagnosis based on national HIV surveillance data from 25 states, United States. Journal of Acquired Immune Deficiency Syndromes 53: 124–130.

Hooshyar D, Hanson DL, Wolfe M et al. (2007) Trends in perimortal conditions and mortality rates among HIV‐infected patients. AIDS 21: 2093–2100.

Hsu DC, Sereti I and Ananworanich J (2013) Serious non‐AIDS events: immunopathogenesis and interventional strategies. AIDS Research and Therapy 10(1): 29.

Hung C‐H, Chang K‐H, Kuo H-C et al. (2012) Features of varicella zoster virus myelitis and dependence on immune status. Journal of the Neurological Sciences 318: 19–24.

Huson MA, Stolp SM, van der Poll T and Grobusch MP (2014) Community‐acquired bacterial bloodstream infections in HIV‐infected patients: a systematic review. Clinical Infectious Diseases 58: 79–92.

Hymes KB, Cheung T, Greene JB et al. (1981) Kaposi's sarcoma in homosexual men‐a report of eight cases. Lancet 2: 598–600.

Jones JL, Hanson DL, Dworkin MS et al. (1999) Surveillance for AIDS‐defining opportunistic illnesses, 1992–1997. MMWR CDC Surveillance Summaries 48: 1–22.

Lawn SD, Meintjes G, McIlleron H, Harries AD and Wood R (2013) Management of HIV‐associated tuberculosis in resource‐limited settings: a state‐of‐the‐art review. BMC Medicine 11: 253.

Lee N (2008) Penicilliosis: an AIDS‐defining disease in Asia. Hong Kong Medical Journal 14: 88–89.

Lienhardt C, Glaziou P, Uplekar M et al. (2012) Global tuberculosis control: lessons learnt and future prospects. Nature Reviews Microbiology 10: 407–416.

Lifson AR, Belloso WH, Davey RT et al. (2010) Development of diagnostic criteria for serious non‐AIDS events in HIV clinical trials. HIV Clinical Trials 11: 205–219.

McNairy ML and El‐Sadr WM (2014) Antiretroviral therapy for the prevention of HIV transmission: What will it take? Clinical Infectious Diseases 58: 1003–1011.

Mesfin YM, Hailemariam D, Biadglign S and Kibret KT (2014) Association between HIV/AIDS and multi‐drug resistance tuberculosis: a systematic review and meta‐analysis. PLoS One 9: e82235.

Mocroft A, Katlama C, Johnson AM et al. (2000) AIDS across Europe, 1994–98: the EuroSIDA study. Lancet 356: 291–296.

Molina JM, Pintado C, Gatey C et al. (2013) Challenges and opportunities for oral pre‐exposure prophylaxis in the prevention of HIV infection: where are we in Europe? BMC Medicine 11: 186.

Nacher M, Adenis A, Mc Donald S et al. (2013) Disseminated histoplasmosis in HIV‐infected patients in South America: a neglected killer continues on its rampage. PLOS Neglected Tropical Diseases 7: e2319.

Post FA, Badri M, Wood R and Maartens G (2001) AIDS in Africa – survival according to AIDS‐defining illness. South African Medical Journal 91: 583–586.

Robbins HA, Shiels MS, Pfeiffer RM and Engels EA (2014) Epidemiologic contributions to recent cancer trends among HIV‐infected peoplein the United States. AIDS 28: 881–890.

Rodger AJ, Lodwick R, Schechter M et al. (2013) Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS 27: 973–979.

Schoffelen AF, van Lelyveld SF, Barth RE et al. (2013) Lower incidence of Pneumocystis jirovecii pneumonia among Africans in the Netherlands host or environmental factors? AIDS (London, England) 27: 1179–1184.

Schwarcz L, Chen MJ, Vittinghoff E, Hsu L and Schwarcz S (2013) Declining incidence of AIDS‐defining opportunistic illnesses: results from 16 years of population‐based AIDS surveillance. AIDS 27: 597–605.

Tobian AA, Kacker S and Quinn TC (2013) Male circumcision: a globally relevant but under‐utilized method for the prevention of HIV and other sexually transmitted infections. Annual Review of Medicine 65: 293–306.

WHO (2013) Global update on HIV treatment 2013: results, impact and opportunities. June 2013 Brief summary. 2013.9 ed2013. Geneva, Switzerland: WHO Press.

World Health Organization (1994) WHO case definitions for AIDS surveillance in adults and adolescents. Weekly Epidemiological Record 69: 273–275.

World Health Organization (2005) Interim WHO Clinical Staging of HIV/AIDS and HIV/AIDS Case Definitions for Surveillance (African Region). Geneva, Switzerland: WHO Press.

World Health Organization (2007) WHO Case Definitions of HIV for Surveillance and Revised Clinical Staging and Immunological Classification of HIV‐Related Disease in Adults and Children. HIV/AIDS Programme. Geneva, Switzerland: WHO Press.

World Health Organization (2013) AIDS and HIV Case Definitions: Overview of Internationally Used HIV/AIDS Case Definitions. Geneva, Switzerland: WHO Press.

Worm SW, Bower M, Reiss P et al. (2013) Non‐AIDS defining cancers in the D:A:D Study – time trends and predictors of survival: a cohort study. BMC Infectious Diseases 13: 471.

Zhou J, Kumarasamy N, Ditangco R et al. (2005) The TREAT Asia HIV observational database: baseline and retrospective data. Journal of Acquired Immune Deficiency Syndromes 38: 174–179.

Further Reading

Bastos FI (2008) Get back to where you once belonged: monitoring the AIDS pandemic in the 21st century. Cien Saude Colet 13(6): 1719–1727.

Cameron E (2005) Witness to AIDS. I.B. Tauris. October 7. South Africa: Tagelberg Publishers Limited. ISBN 978‐1845111199.

De Lay PR (2008) Tailoring AIDS prevention. Science 321(5896): 1631.

Laurence J (2008) Compartmentalizing AIDS. AIDS Reader 18(9): 451–452.

Sharp PM and Hahn BH (2008) AIDS: prehistory of HIV‐1. Nature 455(7213): 605–606.

Shilts R (2007) And the Band Played On, revised edn., November 27. New York: St. Martin's Griffin, St Martin's Press. ISBN 978‐0312374631.

Volberding P, Greene W, Lange J et al. (2013) Sande's HIV/AIDS Medicine: Medical Management of AIDS 2013, 2nd edn. China: Elsevier Saunders. ISBN 978‐1455706952.

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Pinto, Angie N, Kelleher, Anthony D, and Cooper, David A(Jun 2014) AIDS: Clinical Manifestations. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002237.pub3]