The efficacy and safety of zidovudine alone or as cotherapy with acyclovir for the treatment of patients with AIDS and AIDS-related complex: a double-blind randomized trial. European-Australian Collaborative Group.
OBJECTIVE
To evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC).


METHODS
Double-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy.


METHODS
Teaching hospital ambulatory clinics in eight European countries and Australia.


METHODS
A total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988.


METHODS
Time to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4+ cell counts.


RESULTS
During the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, -0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% CI for difference, -0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4+ cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients.


CONCLUSIONS
These data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.
Cooper
D A
DA
National Centre in HIV Epidemiology and Clinical Research, St Vincent's Hospital Medical Centre, Sydney, NSW, Australia.
Pehrson
P O
PO
Pedersen
C
C
Moroni
M
M
Oksenhendler
E
E
Rozenbaum
W
W
Clumeck
N
N
Faber
V
V
Stille
W
W
Hirschel
B
B
D000386:AIDS-Related Complex / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000212:Acyclovir / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D012449:Safety; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D015215:Zidovudine; D000212:Acyclovir