Italian multicentre study of didanosine compassionate use in advanced HIV infection. Italian BMS-906 Study Group

• Published in: European journal of clinical microbiology & infectious diseases 1997-02, Vol.16 (2), p.135
• Main Authors: d'Arminio Monforte, A, Musicco, M, Galli, M, Paga, C, La Regina, A, Lazzarin, A, Angarano, G, Milazzo, F, Gritti, F, Arlotti, M, Mazzotta, F, Visco, G, Aiuti, F, Moroni, M
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - diagnosis; Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - mortality; Adolescent; Adult; Aged; AIDS Dementia Complex - diagnosis; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; CD4 Lymphocyte Count; Didanosine - administration & dosage; Didanosine - adverse effects; Didanosine - therapeutic use; Disease Progression; Drug Resistance, Microbial; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - mortality; Humans; Immunocompromised Host; Italy; Male; Middle Aged; Multivariate Analysis; Pancreatitis - chemically induced; Pancreatitis - diagnosis; Treatment Outcome; Zidovudine - adverse effects; Zidovudine - therapeutic use
• ISSN: 0934-9723

The aim of the present study, a multicentre trial of didanosine (ddI) compassionate use, was to identify factors associated with a better outcome in patients given ddI monotherapy. Enrolled were 1047 HIV-positive patients intolerant of and/or unresponsive to zidovudine (ZDV) therapy, with CD4+ cell counts of < 200/microliter or AIDS. Didanosine was given at a dose of 250 mg b.i.d. (patients > or = 60 kg) or 167 mg b.i.d. (patients < 60 kg). Clinical examinations and laboratory tests were performed every two months. Endpoints included death, the occurrence of a new AIDS-defining disease, or permanent discontinuation of ddI for a severe adverse event. At entry, the median CD41 cell count was 47/microliter and the median duration of prior ZDV treatment 19 months; 446 patients (43%) were classified as having AIDS. Severe toxicity occurred in 143 subjects (14%); the frequency of pancreatitis was very low (0.2%). The benefit in terms of CD4+ cell counts was greater for patients whose counts exceeded 100/microliter at entry and remained at this level until month 12 in those patients still receiving treatment. Death and/or new AIDS-defining events were observed in 374 cases (36%) over a median follow-up of eight months. AIDS dementia was observed in 11 patients (1%). Multivariate analysis of survival without disease progression showed that the factors associated with a worse outcome include the severity of immunodepression, a diagnosis of AIDS at entry, and a history of both intolerance of and clinical resistance to ZDV. Surprisingly, the patients who had received previous prolonged treatment with ZDV had a better outcome. In conclusion, severely immunodepressed patients previously administered long-term monotherapy may receive a short-term benefit from being switched to another antiretroviral drug.