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Features of AIDS and AIDS defining diseases during the highly active antiretroviral therapy (HAART) era, compared with the pre-HAART period: a case-control study
  1. Roberto Manfredi,
  2. Francesco Chiodo
  1. Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna, Bologna, Italy
  1. Dr Roberto Manfredi, Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna, S Orsola Hospital, Via Massarenti, 11, I-40138 Bologna, Italy

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Editor,—To assess the features of AIDS defining illnesses during the HAART era versus those observed before the introduction of HAART, the characteristics of 72 consecutive patients, diagnosed in 1997–9, were compared with those of 144 subjects randomly selected from the 436 patients diagnosed from 1985 to 1995, in a case-control study.

An impressive drop in AIDS diagnosis was seen shortly after the introduction of HAART, with only 38, 21, and 13 cases per ∼1000 patient years observed in 1997, 1998, and 1999 respectively, versus a mean frequency >60 cases per ∼1000 patient years, demonstrated during 1991–5. A tendency towards an increased incidence of female sex was shown in 1997–9 compared with 1985–95 (33.3% versus 27.1%), together with a rise of mean CD4+ lymphocyte count (86.8 (SD 99.4) versus 72.1 (93.7) cells ×106/l), while an increase in the mean patient age was highly significant (39.8 (8.3) versus 34.6 (7.7) years; p<0.0001). When considering the exposure to HIV infection, drug abuse became significantly less important in the HAART era (p<0.05), while heterosexual transmission was notably increased (34.7% versus 13.2% of cases; p<0.0003). The distribution of AIDS defining disorders during the HAART era showed an tendency to a reduction in cytomegalovirosis, cryptococcosis, mycobacteriosis, cryptosporidiosis, and HIV encephalopathy, while a relative increase in pneumocystosis, oesophageal candidiasis, wasting syndrome, tuberculosis, and non-Hodgkin's lymphoma was found; neurotoxoplasmosis and Kaposi's sarcoma were stable (table 1). However, while pneumocystosis, Candida oesophagitis, neurotoxoplasmosis, and Kaposi's sarcoma represented the four most frequent AIDS related events in both study periods, cytomegalovirosis, HIV encephalopathy, cryptococcosis, and mycobacteriosis (which ranked fifth to eighth in frequency during the pre-HAART era), virtually disappeared after the introduction of HAART (28 versus four overall cases; p<0.007), together with cryptosporidiosis. Neoplasms and HIV related disorders (encephalopathy and wasting syndrome), showed a slightly increased frequency during the HAART era (16.8% and 9.2% during 1997–9, versus 13.2% and 7.9% respectively, during the pre-HAART period). A considerable trend to increased mean CD4+ count was found during the HAART era for all AIDS related illnesses considered, except neurotoxoplasmosis. However, this increase in CD4+ count was significant only for Candida oesophagitis (p<0.04), wasting syndrome (p<0.03), and tuberculosis (p<0.03), probably because of small patient samples. Only seven of the 72 patients who developed AIDS since 1997 (9.7%), were effectively treated with HAART for more than 3 months before diagnosis; in the remaining 65 cases HIV infection was detected concurrently with an AIDS defining event in subjects who were unaware of their condition (40 cases), or refused HAART or carried out it with poor adherence (25 patients).

Although a sharp decline in the incidence of multiple AIDS defining events was demonstrated since the introduction of HAART, the distribution of primary AIDS associated diseases showed limited modifications.13 An increased incidence of women, a higher patient age, a greater role for heterosexual transmission compared with injecting drug addiction, and a rise in CD4+ count were disclosed by us in the HAART era compared with the pre-HAART period. Appreciable modifications of the spectrum of AIDS associated illnesses were also observed during the HAART era (a drop of cytomegalovirosis, cryptococcosis, mycobacteriosis, cryptosporidiosis, and HIV encephalopathy, with a parallel increase in pneumocystosis, oesophageal candidiasis, wasting syndrome, tuberculosis, and non-Hodgkin's lymphoma), together with a considerable trend towards an increased mean CD4+ count at diagnosis, as previously noted.2, 5 Disorders which are directly or indirectly associated with HIV damage itself, AIDS related neoplasms, and opportunistic diseases occurring with a less profound immunodeficiency, show a substantially stable or even increasing incidence among newly diagnosed cases of AIDS.1, 2, 4 However, opportunistic diseases related to a severe immunodeficiency are still frequent among AIDS defining events, since the majority of cases identified during the HAART era occur in patients who are not aware of their disease, or fail HAART. Only early detection and aggressive treatment of HIV infection may definitively improve the epidemiology of AIDS; a continued surveillance of AIDS related disorders remains critical for the implementation of therapeutic and prophylactic strategies.

Table 1

AIDS defining events and mean CD4+ lymphocyte count at disease occurrence, in the two considered time periods


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