Meta-analysis of five randomized controlled trials comparing continuation of zidovudine versus switching to didanosine in HIV-infected individuals.
A meta-analysis of the original data from 2411 patients in the ACTG 116A, ACTG116B/117, ACTG175, BMS010 and CTN002 trials was conducted to improve the estimate of the effect of switching from zidovudine to didanosine on rates of clinical progression, to better quantify the rates of neurological events (including AIDS dementia and peripheral neuropathy) and to examine the effects of switching from zidovudine to didanosine among women and racial subgroups. In total, 1012 patients received zidovudine therapy, 557 received high-dose didanosine and 842 received didanosine. The median duration of follow-up was 15 months. Ninety-one percent of patients were male, 78% were white, mean age was 36.5 years. The median CD4 count was 195 cells/mm3 (range: 0-762) and the median duration of prior zidovudine therapy was 14 months (range: 0.1-94). There were 336 deaths and 686 new AIDS-defining illnesses (ADIs) or deaths. After stratification by study and adjusting for baseline CD4 count and presence of an AIDS diagnosis prior to baseline, the relative risks of death associated with switching from zidovudine to high-dose didanosine or to didanosine were 0.94 (P = 0.64) and 0.77 (P = 0.07), respectively. The relative risks of a new ADI or death associated with switching from zidovudine to high-dose didanosine and didanosine were 0.78 (P = 0.01) and 0.66 (P = 0.0001), respectively. There were 21 documented cases of AIDS dementia complex (ADC) during the entire follow-up period. The rates per 100 person years of follow-up were 0.70, 0.65 and 0.41 for the zidovudine, high-dose didanosine and didanosine arms, respectively. There were no significant differences in risks of ADC between treatment arms (zidovudine versus high-dose didanosine: P = 0.30, zidovudine versus didanosine: P = 0.97, didanosine versus high-dose didanosine: P = 0.41). Our data confirm a clinical benefit and CD4 increase associated with a switch from zidovudine to didanosine therapy. No statistical differences were detected between doses of didanosine with respect to survival or progression to a new ADI or death. Furthermore, there was no statistical difference in the frequency of ADC between treatment arms.
Raboud
J M
JM
University of British Columbia, St. Paul's Hospital, Vancouver, Canada. jraboud@hivnet.ubc.ca
Montaner
J S
JS
Rae
S
S
Kahn
J
J
Hammer
S M
SM
Katzenstein
D A
DA
Pavia
A
A
Dolin
R
R
Hughes
M D
MD
Cross
A
A
Beltangady
M
M
Gatell
J
J
Dunkle
L
L
Smaldone
L
L
D015526:AIDS Dementia Complex / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D015994:Incidence; D016032:Randomized Controlled Trials as Topic; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D015215:Zidovudine; D016049:Didanosine