Acquired immunodeficiency without evidence of HIV infection: national retrospective survey

BMJ 1994; 308 doi: (Published 26 March 1994) Cite this as: BMJ 1994;308:825
  1. A McNulty, venereologist,
  2. J M Kaldor, deputy director,
  3. A M McDonald, senior research assistant,
  4. K Baumgart, clinical immunologist,
  5. D A Cooper, director
  1. National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW, Australia
  2. J M Kaldor, deputy director A M McDonald, senior research assistant D A Cooper, director National Health and Medical Research Council Post Graduate Medical Research School, Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, NSW, Australia K Baumgart, clinical immunologist.
  1. Correspondence to: Dr Kaldor. Taylor Square Private Clinic, Darlinghurst, NSW, Australia

    The term idiopathic CD4 T lymphocytopenia has been introduced to describe the syndrome of depletion of CD4 lymphocytes in people with no evidence of HIV infection or other explanation for immunodeficiency.1 We report a retrospective national survey to identify and characterise cases of unexplained CD4 lymphocytopenia in Australia.


    and results

    The National Centre in HIV Epidemiology and Clinical Research asked all specialists in clinical immunology and infectious diseases and other medical practitioners known to have an interest in immune disorders to provide information on any patient who had been diagnosed as immunodeficient on or after 1 January 1985 on the basis of a reduced CD4 lymphocyte count (no specific value was defined) or specific illnesses related to cell mediated immunodeficiency. The patients had to have had a negative result on serological testing for HIV-1 infection, and congenital conditions and immunosuppressive treatment had to have been excluded as causes of immunodeficiency.

    Overall, 96 practitioners were contacted in writing. The 42 specialists in infectious diseases and clinical immunology who did not submit a case were contacted by telephone. Twelve case reports were submitted, of which seven satisfied the definition of idiopathic CD4 T lymphocytopenia, with a CD4 lymphocyte count of <300 x 106/1 or <20% of total lymphocytes on more than one occasion (table).1 Supplemental tests (polymerase chain reaction and culture) for HIV-1 infection in three cases and tests for HIV-2 infection in four yielded negative results.

    Reported cases of acquired immunodeficiency without evidence of HIV infection in Australia, 1985-92

    View this table:

    Five patients had cryptococcosis (three at extrapulmonary sites). The three cases for which results of serotyping were available were due to Cryptococcus neoformans var neoformans. Only one patient (case 1) gave a history of exposure to a factor associated with an increased risk of HIV infection: he had received multiple blood transfusions during 1982-3.

    CD4 lymphocyte counts six months after the diagnosis of immunodeficiency were available in all cases. In all except one (case 6) CD4 lymphocytes as a percentage of total lymphocytes remained <20%. In three cases (3, 5, and 7) the absolute CD4 lymphocyte count was >300 X106/1. All seven patients were alive one year after diagnosis.


    Acquired immunodeficiency had been diagnosed in five of the cases during 1990-2 and in only two during 1985-9. Cases of idiopathic CD4 T lymphocytopenia may simply be rare cases of unexplained immunodeficiency reported by doctors familiar with HIV infection and with ready access to laboratories that perform CD4 lymphocyte estimations. Attention in the lay and medical press may also have encouraged recall and reporting of cases.

    Increased use of T lymphocyte counts in the investigation of unexplained symptoms of apparent immunodeficiency has led to cautions against the overinterpretation of results.2 Of the patients reported on here, the two with the most recent diagnosis of immunodeficiency (in 1992) had the least clinical evidence of immunodeficiency.

    Five of the seven patients in our series had cryptococcal disease. Muller argued that the polysaccharide capsule of C neoformans is immunosuppressive, possibly resulting in lowered CD4 lymphocyte counts secondary to the infection itself.3 As we do not know the CD4 lymphocyte counts before cryptococcosis occurred we cannot evaluate this hypothesis.

    The patients' exposure histories had little in common with the reported histories of people with AIDS in Australia, most of whom seem to have acquired HIV infection through homosexual contact.4

    Our series highlights some of the difficulties associated with the definition of idiopathic CD4 T lymphocytopenia. CD4 lymphocyte counts may vary widely both within and among people, whether immunocompromised or not, although counts persistently below 300 X 106/1 seem to be rare in the absence of an identified cause of immunosuppression.5 The definition of idiopathic CD4 T lymphocytopenia requires more than one abnormally low count, but the interval between the measurements is not specified. CD4 lymphocyte counts during or after certain opportunistic infections may be transiently lowered as a direct effect of the infecting organism.

    The National Centre in HIV Epidemiology and Clinical Research is supported by the Australian National Council on AIDS through the Commonwealth AIDS Research Grants Committee. We thank Drs Robert Finlayson, Paul Gatenby, Peter Hollingsworth, Jenny Hoy, Justin Labrooy, Don Packham, John Quin, Dennis Rhodes, Denis Spelman, Ron Walls, and Paul Zilko for contributing reports on the cases reviewed in this paper; Ms Jenny Learmont and Drs Debbie Marriot and Sharon Chen for help in providing background information; and Dr Brett Tindall for comments on an earlier draft.


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