Italian multicentre study of didanosine compassionate use in advanced HIV infection. Italian BMS-906 Study Group.
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.
d'Arminio Monforte
A
A
Clinic of Infectious Diseases, University of Milan, L. Sacco Hospital, Italy.
Musicco
M
M
Galli
M
M
Paga
C
C
La Regina
A
A
Lazzarin
A
A
Angarano
G
G
Milazzo
F
F
Gritti
F
F
Arlotti
M
M
Mazzotta
F
F
Visco
G
G
Aiuti
F
F
Moroni
M
M
D015526:AIDS Dementia Complex / Q000175:diagnosis; D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004352:Drug Resistance, Microbial; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D016867:Immunocompromised Host; D007558:Italy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010195:Pancreatitis / Q000139:chemically induced / Q000175:diagnosis; D016896:Treatment Outcome; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine; D016049:Didanosine