The case for indicator condition-guided HIV screening


Correspondence: Prof. Jeffrey V. Lazarus, Copenhagen HIV Programme, Copenhagen University, Panum Institute, Bldg 21.1, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark. Tel: +45 5152 9926; fax: +45 3545 5758; e-mail:


One-half of the estimated 2.5 million people who now live with HIV in the World Health Organization (WHO) European Region are still diagnosed late. A central question is which clinical scenarios should trigger an HIV test recommendation in order to avoid late presentation. Drawing on the work of the HIV Indicator Diseases across Europe Study (HIDES), new guidance brings together in one place a list of the conditions that should result in an HIV screening recommendation.


In 1977, fatigued, and suffering from lymphadenopathy and Pneumocystis carinii infection, physician Grethe Rask died in Copenhagen, Denmark [1]. Rask had been working in what was then Zaire when she became ill and, in 1984, retrospective testing of preserved samples confirmed her as the first reported person to die of AIDS in the European Region. Thirty-five years later, in March 2012, some 300 HIV researchers, advocates and policymakers gathered across the street from the hospital where Rask died to discuss why around one-half of the 2.5 million people who now live with HIV in the Region still present late1 for testing [3] − despite the widespread availability of free screening − and what can be done to reduce this number.

The great success story in HIV testing has been that of antenatal testing. Where it has become a routine recommendation of clinical care, the offer of a test, patient acceptance and uptake have been very high. The lesson for other indicator conditions is that patients do not like to feel that they are being singled out. Yet, while mother-to-child transmission has been virtually eliminated in much of the European Region, many testing gaps persist in both eastern and western Europe. For example, French medical records revealed that, among newly diagnosed HIV-infected patients, not only had 82% of those who sought care for an HIV symptom in the 3 years preceding diagnosis not received an HIV test, but neither had 55% of men who reported having sex with other men to their provider, in spite of World Health Organization (WHO) guidance on the importance of HIV testing for these men [4].


For health care providers, a central question is: Which clinical scenarios should trigger an HIV test? Since 2006, the US Centers for Disease Control and Prevention (CDC) has recommended routine HIV testing in all health care settings, except where the prevalence of undiagnosed HIV infection has been documented as less than 0.1% [5], and in 2007 WHO issued guidance stating that ‘health care providers should recommend HIV testing and counselling as part of the standard of care to all adults, adolescents or children who present to health facilities with signs, symptoms or medical conditions that could indicate HIV infection. These include, but are not necessarily limited to, tuberculosis and other conditions specified in the WHO HIV clinical staging system [6].’ While globally routine HIV testing is increasingly being implemented for patients presenting with tuberculosis (TB), sexually transmitted infections (STIs), pregnancy, or AIDS-defining conditions such as Kaposi's sarcoma, it tends to stop there. A European screening strategy that targets a broader range of clinical signs, symptoms and comorbidities associated with HIV infection would reduce late diagnoses even further.

The Copenhagen assembly – the 2012 conference of the HIV in Europe Initiative [7] – introduced just such a strategy in new HIV screening guidance for health care providers. Drawing on the work of the HIV Indicator Diseases across Europe Study (HIDES), which is funded and run by the HIV in Europe Initiative, the guidance brings together in one place a list of the conditions for which evidence, including expert opinion, supports routine HIV screening [8]. The guidance has been developed by a panel of experts, including representatives from medical specialties other than infectious diseases, recognizing the challenge of implementing the strategy in health care settings where an HIV test offer has not been a part of routine clinical screening.

The conditions fall into three categories. The list of AIDS-defining conditions should be familiar to most clinicians. In seropositive individuals, the presence of one of these conditions indicates such severe impairment of the immune system that it is used to define progression to AIDS [9]. As correct management includes immediate initiation of antiretroviral therapy, a failure to test for HIV upon presentation with one of these conditions amounts to substandard care.

Conditions associated with an undiagnosed HIV prevalence of >0.1% include both conditions for which there is evidence of a high HIV prevalence (e.g. lymphoma, herpes zoster and STIs), for which HIV testing is strongly recommended, and those for which, in the absence of published evidence, expert opinion deems a high HIV prevalence likely, and for which HIV testing is recommended to be offered. In assessing conditions for inclusion in this category, the guide's advisory panel defined high prevalence as a rate of previously undiagnosed HIV infections of at least 0.1%, which various French and American studies have suggested as being cost-effective in these settings [10, 11]. The list of conditions and recommendations for testing will be updated based on future evidence of HIV prevalence (HIDES II).

Finally, the category of Conditions where not identifying the presence of HIV infection may have significant adverse implications for the individual's clinical management covers patients who are about to initiate aggressive immunosuppressive treatment and who have primary space-occupying brain lesions.

What is most striking about the more than 50 conditions listed is their variety. In addition to a host of conditions that all clinicians should familiarize themselves with, there are also conditions most likely to be seen by specific specialists, such as pulmonologists, neurologists and dentists (see Table 1), posing a significant challenge to increasing the frequency of the offer of an HIV test.

Table 1. Indicator conditions and specialties involved
SpecialtyIndicator conditions
  1. 1Conditions that are AIDS-defining among people living with HIV.
  2. 2Conditions associated with an undiagnosed HIV prevalence of ≥ 0.1% or an undiagnosed HIV prevalence that is considered likely to be >0.1%.
  3. 3Conditions where not identifying the presence of HIV infection may have significant adverse implications for the individual's clinical management despite the estimated prevalence of HIV being likely to be < 0.1%.
Respiratory medicine/pulmonology


Pneumocystis carinii pneumonia1

Pneumonia, recurrent1

Mycobacterium avium complex (MAC) lung disease1

Histoplasmosis, disseminated/extrapulmonary1

Herpes simplex bronchitis/pneumonitis1

Candidiasis bronchial/pulmonary1

Community-acquired pneumonia2

Neurology and neurosurgery

Cerebral toxoplasmosis1

Cryptococcosis, extrapulmonary1

Progressive multifocal leucoencephalopathy1

Reactivation of American trypanosomiasis (meningoencephalitis or myocarditis)1

Guillain–Barré syndrome2


Subcortical dementia2

Multiple sclerosis-like disease2

Peripheral neuropathy2

Primary space-occupying lesion of the brain3

Dermatology/dermatovenereology/genitourinary medicine

Kaposi's sarcoma1

Herpes simplex ulcer(s)1

Atypical disseminated leishmaniasis1

Penicilliosis, disseminated1

Seborrheic dermatitis/exanthema2

Herpes zoster2

Sexually transmitted infections2

Hepatitis B or C (acute or chronic)2

Severe or recalcitrant psoriasis2




Cryptosporidiosis diarrhoea, >1 month1

Microsporidiosis, >1 month1

Isosporiasis, >1 month1

Candidiasis, oesophageal1

Hepatitis B or C (acute or chronic)2

Unexplained chronic diarrhoea2


Lymphoma, non-Hodgkin1

Kaposi's sarcoma1

Primary lung cancer2

Anal cancer/dysplasia2

Cancer requiring aggressive immunosuppressive therapy3


Cervical cancer1

Sexually transmitted infections2

Hepatitis B or C (acute or chronic)2

Pregnancy (implications for the unborn child)2

Cervical dysplasia2


Lymphoma, non-Hodgkin1

Malignant lymphoma2

Unexplained leukocytopenia/thrombocytopenia lasting >4 weeks2

Thrombotic thrombocytopenic purpura3

Infectious diseases/internal medicine


Mycobacterium tuberculosis, pulmonary or extrapulmunary1

Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary1

Mycobacterium, other species or unidentified species, disseminated or extrapulmunary1

Pneumonia, recurrent (two or more episodes in 12 months)1

Pneumocystis carinii pneumonia1

Cryptococcosis, extrapulmonary1

Salmonella septicaemia1

Cytomegalovirus, other (except liver, spleen or glands)1

Herpes simplex ulcer(s) >1 month with bronchitis/pneumonitis1

Candidiasis bronchial/tracheal/pulmonary1

Candidiasis, oesophageal1

Histoplasmosis, disseminated/extrapulmonary1

Coccidiodomycosis, disseminated/extrapulmonary1

Atypical disseminated leishmaniasis1

Reactivation of American trypanosomiasis (meningoencephalitis or myocarditis)1

Penicilliosis, disseminated1

Sexually transmitted infection2

Hepatitis B or C (acute or chronic)2

Mononucleosis-like illness2

Invasive pneumococcal disease2

Herpes zoster2

Lymphocytic meningitis2

Visceral leishmaniasis2

Unexplained weight loss2

Unexplained fever2

Unexplained chronic diarrhoea2

Unexplained lymphadenopathy2

Unexplained leukocytopenia/thrombocytopenia lasting >4 weeks2

RheumatologyAutoimmune disease treated with aggressive immunosuppressive therapy3
OphthalmologyCytomegalovirus retinitis1

Candidiasis tracheal/oesophageal1

Mononucleosis-like illness2

NephrologyUnexplained chronic renal impairment2
General practiceSymptomatology fitting any of the listed conditions
Emergency medicineSymptomatology fitting any of the listed conditions

Oral hairy leukoplakia2

Candidiasis, oral and oesophageal1

Kaposi's sarcoma1

The first phase of HIDES investigated the undiagnosed HIV prevalence in European patients presenting with a condition taken from a group of eight different diseases and disease clusters associated with HIV infection. It found prevalence rates ranging from 0.29% for malignant lymphoma to 3.85% for persistent mononucleosis-like illness and 4.06% for STIs [12]. Phase II (2012–2013) will expand testing to additional sites (>50) and indicator diseases across the European Region with the aim of screening 14 000 patients presenting with one of 11 indicator diseases (see for details).


Early HIV diagnosis and treatment have clear individual and public health benefits. Late diagnosis and late treatment are associated with substantial increases in morbidity and mortality, health care costs and onward transmission [13-15]. The broad implementation of indicator condition-guided HIV testing is one way to increase the detection rate and provides an invaluable complement to the targeted testing of risk groups. Further, indicator condition-guided testing can significantly reduce both provider and partner barriers and can reduce stigma among both.

The guidance was published in October 2012 by the HIV in Europe Initiative (, and they are promoting its implementation through European and national medical societies and policy organizations as well as in medical training and health care facilities throughout the Region, particularly in settings where staff are not accustomed to screening for HIV.


The authors would like to acknowledge all of the contributors to HIV indicator conditions: guidance for implementing HIV testing in adults in health care settings and the participants at the HIV in Europe Copenhagen 2012 Conference. In addition, we would like to thank Miriam Lewis Sabin for her constructive comments on this piece.

Conflicts of interest

The authors declare that they have no competing interests.

Author contributions: JVL and MH conceived of the idea and developed the first draft with support from DR. VD, TC and JDL reviewed and commented on the draft and played an important role, along with DR, in developing the guidance itself. All authors have read and approved the final manuscript.


  1. 1

    Late presentation consensus definition: persons presenting for care with a CD4 count below 350 cells/μL or presenting with an AIDS-defining event, regardless of the CD4 cell count [2].