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

Subjects, methods, and results

In January 1993 the Italian National AIDS Unit began a nationwide retrospective survey of symptomatic cases of acquired immunodeficiency without HIV infection. Cases were defined as having (a) one or more clinical conditions indicating severe immunosuppression; (b) depleted CD4 T lymphocytes (fewer than 300x10 6 cells/l or proportionately less than 20% of the lymphocyte count) at the time of clinical diagnosis; (c) no known cause of immunosuppression; and (d) negative results for HIV infection on enzyme linked immunosorbent assay (ELISA) and in at least one supplementary test. This case definition was circulated to all doctors who were considered most likely to have seen such patients--namely, immunologists and specialists in infectious diseases who had reported a high number of AIDS cases--in a letter asking them to compile standardised case reports.

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

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

Candidiasis was the most common opportunistic disease. All patients were negative for HIV-1 antibody and p24 antigen on ELISA. Western blotting for HIV-1 antibody and ELISA for HIV-2 antibody were performed in eight cases. In five cases supplementary techniques were used (culture (three cases), polymerase chain reaction (two)) and gave negative results. Nine patients had a CD4 count of less than 300x106 cells/l, the remaining patient (case 8) had a fairly high count, but it was proportionally less than 20% of the total lymphocyte count.

Four of the patients died during a median follow up time of 31.5 months (range: 6-66 months); the causes of death were opportunistic infections (in two), lymphoma, and vascular encephalopathy (stroke). The median survival time by Kaplan-Meier analysis was about 50 months. Of the survivors, only one showed a large decrease in the number of CD4 cells during follow up (from 167 to 94x10 6 cells/l); counts remained stable in the others.

Comment

Our survey found a few sporadic cases of acquired immunodeficiency without evidence of HIV infection. Only one patient reported typical risk factors for HIV infection, and there was no evidence of clusters or sexual transmission. The clinical characteristics of these patients were similar to those of people with HIV infection and AIDS, except that our patients had higher CD4+ counts at the time of diagnosis. Patients with acquired immunodeficiency without 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 HIV infection is a sporadic phenomenon that does not seem to be associated with a single infectious agent. Though our patients tended to survive longer than patients with HIV infection and AIDS, survival times were highly variable. Follow up studies of larger populations are needed to define more clearly acquired immunodeficiency 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 AIDS of the World Health Organisation for giving us the case report form that we modified for data collection in this survey.