Acquired immunodeficiency without HIV infection: epidemiology and clinical outcome in Italy

BMJ 1995;311:785-786 (23 September)

Papers

Acquired immunodeficiency without HIV infection: epidemiology and clinical outcome in Italy

G Rezza, director,^a P Pezzotti, research assistant,^a F Aiuti, director,^b for the Italian Study Group on non-HIV AIDS

^a Centro Operativo AIDS, Istituto Superiore di Sanita, 00161 Rome, ^b Cattedra di Allergologia e Immunologia Clinica, Universita La Sapienza, 00162 Rome

Members of the study group are given at the end of the report. Correspondence to: Dr Rezza.

Cases of acquired immunodeficiency without HIV infection, butwith depletion of CD4 T lymphocytes have been reported since1989. We estimated the prevalence of this condition in Italyand evaluated its clinical outcome.

Subjects, methods, and results

In January 1993 the Italian National AIDS Unit began a nationwideretrospective survey of symptomatic cases of acquired immunodeficiencywithout HIV infection. Cases were defined as having (a) oneor more clinical conditions indicating severe immunosuppression;(b) depleted CD4 T lymphocytes (fewer than 300x10⁶ cells/l orproportionately less than 20% of the lymphocyte count) at thetime of clinical diagnosis; (c) no known cause of immunosuppression;and (d) negative results for HIV infection on enzyme linkedimmunosorbent assay (ELISA) and in at least one supplementarytest. This case definition was circulated to all doctors whowere considered most likely to have seen such patients--namely,immunologists and specialists in infectious diseases who hadreported a high number of AIDS cases--in a letter asking themto compile standardised case reports.

Up to 30 June 1994, 13 case reports had been received from allover Italy. Two cases were immediately excluded because theydid not meet diagnostic criteria; another case was later excludedbecause the patient developed sarcoidosis. The year of diagnosisof the 10 confirmed cases is reported in the table. The meanage was 47.3 years (range: 38-59); seven of the 10 cases werereported among men.

Only one patient (case 1) reported risk factors for HIV infection;another patient (case 6) came from Ethiopia and has been reportedon previously. None of the patients reported injecting drugmisuse, which is the most common risk factor for HIV infectionin Italy. Eight patients had a regular sexual partner; fourof the partners tested negative for HIV-1 and HIV-2 antibodies(the other four partners were not tested). None of the membersof the patients' extended families had serious infections orproblems with their immune system.

Characteristics of and outcome in Italian patients with acquired immunodeficiency without HIV infection
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                                                               Lymphocyte                                                                 Outcome+
         Sex, age                                                count           CD4 count            CD8 count             Year of    (last CD4 count
Case No  (years)        Opportunistic disease                    x10⁶/l    x10⁶/l (%)*    x10⁶/l (%)*    diagnosis      (x 10⁶/l))
------------------------------------------------------------------------------------------------------------------------------------------------------------
 1++      M, 38     Kaposi's sarcoma                             1130            280 (24.8)           740 (65.5)             1989         Alive (280)
 2        F, 40     Herpes simplex virus infection, condylomas    864            224 (25.9)           346 (40.0)             1989         Alive (333)
 3        M, 47     Oesophageal candidiasis, salmonellosis       1451            270 (18.6)           522 (36.0)             1990         Alive (322)
 4        F, 46     Oesophageal candidiasis, pneumonia            966             10 (1.0)            179 (18.5)             1990         Dead
 5        M, 48     Herpes simplex virus infection, oesophageal  1620            162 (10.0)           470 (29.0)             1992         Dead
                     candidiasis, lymphoma, shingles
 6        M, 53     Pulmonary tuberculosis, oral candidiasis      981            206 (21.0)           186 (19.0)             1993         Alive (NAc)
 7        M, 53     Neurotoxoplasmosis, disseminated             1410            273 (19.4)          1188 (84.3)             1993         Dead
                     cytomegalovirus infection, lymphoma,
                     Kaposi's sarcoma
 8        M, 39     Wasting syndrome, Pneumocystis carinii       2552            434 (17.0)          1378 (54.0)             1993         Dead
                     pneumonia, neurotoxoplasmosis,
                     disseminated cytomegalovirus infection
 9        F, 50     Pulmonary and bone tuberculosis               436            167 (38.3)           167 (38.3)             1994         Alive (94)
10        M, 59     Cryptococcal meningitis                       186             15 (8.1)            100 (53.8)             1994         Alive (42)
-----------------------------------------------------------------------------------------------------------------------------------------------------------
*Of lymphocyte count.                                     ++Risk factor for HIV infection (male to male sexual intercourse).
+By December 1994.                                        cMissing data--no follow up measure available.

Candidiasis was the most common opportunistic disease. All patientswere negative for HIV-1 antibody and p24 antigen on ELISA. Westernblotting for HIV-1 antibody and ELISA for HIV-2 antibody wereperformed in eight cases. In five cases supplementary techniqueswere used (culture (three cases), polymerase chain reaction(two)) and gave negative results. Nine patients had a CD4 countof less than 300x10⁶ cells/l, the remaining patient (case 8)had a fairly high count, but it was proportionally less than20% of the total lymphocyte count.

Four of the patients died during a median follow up time of31.5 months (range: 6-66 months); the causes of death were opportunisticinfections (in two), lymphoma, and vascular encephalopathy (stroke).The median survival time by Kaplan-Meier analysis was about50 months. Of the survivors, only one showed a large decreasein the number of CD4 cells during follow up (from 167 to 94x10⁶cells/l); counts remained stable in the others.

Comment

Our survey found a few sporadic cases of acquired immunodeficiencywithout evidence of HIV infection. Only one patient reportedtypical risk factors for HIV infection, and there was no evidenceof clusters or sexual transmission. The clinical characteristicsof these patients were similar to those of people with HIV infectionand AIDS, except that our patients had higher CD4+ counts atthe time of diagnosis. Patients with acquired immunodeficiencywithout HIV infection survived longer than patients with AIDS,whose survival time is about 15 months in Italy.⁵

Our study confirms that acquired immunodeficiency without HIVinfection is a sporadic phenomenon that does not seem to beassociated with a single infectious agent. Though our patientstended to survive longer than patients with HIV infection andAIDS, survival times were highly variable. Follow up studiesof larger populations are needed to define more clearly acquiredimmunodeficiency without HIV infection and its clinical variability.

The Italian Study Group on non-HIV AIDS also includes F Dammaco(Bari), S Casari (Brescia), R Finazzi (Milan), E Guerra (Rome),A Lazzarin (Milan), F Montella (Rome), E Pizzigallo (Chieti),and A Sinicco (Turin). We thank the Global Programme on AIDSof the World Health Organisation for giving us the case reportform that we modified for data collection in this survey.

Funding: In part a grant from the Progetto AIDS, Ministero dellaSanita-Istituto Superiore di Sanita.

Conflict of interest: None.