TY - JOUR
T1 - Safety and antiviral activity of combination therapy with zidovudine, zalcitabine, and two doses of interferon-α2a in patients with HIV
AU - Fischl, Margaret A.
AU - Richman, Douglas D.
AU - Saag, Michael
AU - Meng, Tze Chiang
AU - Squires, Kathleen E.
AU - Holden-Wiltse, Jeanne
AU - Meehan, Patricia M.
PY - 1997/12/1
Y1 - 1997/12/1
N2 - We conducted a three-arm, randomized, phase II study to evaluate the combination of zidovudine (600 mg/day) and zalcitabine (2.25 mg/day) alone or with one of two interferon-α(2a) doses (1 mIU or 6 mIU daily). Primary study endpoints included toxicity and changes from baseline for plasma HIV-1 RNA, CD4 cells, and quantitative microculture at weeks 8 and 24. Sixty-three patients with HIV infection and <400 CD4 cells/mm3 were enrolled; four patients discontinued therapy within 2 weeks. Adverse event rates were 37%, 32%, and 60%, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups. Increasing doses of interferon resulted in significantly greater hematologic toxicity (p = 0.03) and peripheral neuropathy (p = 0.02). Plasma HIV-1 RNA reductions were noted across all treatment groups at week 8 (p < 0.001) but only for the nucleoside and 1-mIU interferon combination groups at week 24 (p < 0.001). Mean reductions in HIV- 1 RNA at week 8 were 0.94, 1.29, and 1.40 log10, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups (p = 0.05); no differences were noted at week 24. No differences in CD4 cell counts were seen. The addition of interferon-α(2a) to zidovudine and zalcitabine resulted in transient enhanced decreases in viral load and increased toxicity.
AB - We conducted a three-arm, randomized, phase II study to evaluate the combination of zidovudine (600 mg/day) and zalcitabine (2.25 mg/day) alone or with one of two interferon-α(2a) doses (1 mIU or 6 mIU daily). Primary study endpoints included toxicity and changes from baseline for plasma HIV-1 RNA, CD4 cells, and quantitative microculture at weeks 8 and 24. Sixty-three patients with HIV infection and <400 CD4 cells/mm3 were enrolled; four patients discontinued therapy within 2 weeks. Adverse event rates were 37%, 32%, and 60%, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups. Increasing doses of interferon resulted in significantly greater hematologic toxicity (p = 0.03) and peripheral neuropathy (p = 0.02). Plasma HIV-1 RNA reductions were noted across all treatment groups at week 8 (p < 0.001) but only for the nucleoside and 1-mIU interferon combination groups at week 24 (p < 0.001). Mean reductions in HIV- 1 RNA at week 8 were 0.94, 1.29, and 1.40 log10, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups (p = 0.05); no differences were noted at week 24. No differences in CD4 cell counts were seen. The addition of interferon-α(2a) to zidovudine and zalcitabine resulted in transient enhanced decreases in viral load and increased toxicity.
KW - Combination therapy
KW - HIV infection
KW - Interferon
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U2 - 10.1097/00042560-199712010-00005
DO - 10.1097/00042560-199712010-00005
M3 - Article
C2 - 9402071
AN - SCOPUS:0030734519
VL - 16
SP - 247
EP - 253
JO - Journal of acquired immune deficiency syndromes (1999)
JF - Journal of acquired immune deficiency syndromes (1999)
SN - 1525-4135
IS - 4
ER -