Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. Wellcome Resistance Study Collaborative Group.
A randomized controlled study was done to determine whether initial combination therapy with zidovudine and zalcitabine or zidovudine and didanosine would delay the emergence of zidovudine-resistant virus. Human immunodeficiency virus (HIV)-1-infected patients with <300 CD4 cells/mm3 and <4 weeks of prior zidovudine therapy were randomized to zidovudine, zidovudine plus zalcitabine, or zidovudine plus didanosine. Combination therapy did not delay the emergence of zidovudine-resistant virus isolates. However, combination therapy resulted in a significant increase in CD4 cells through 72 weeks compared with zidovudine monotherapy and a greater and more sustained decline in serum HIV-1 RNA. Although this trial was not designed as a clinical end-point study, patients assigned to zidovudine plus didanosine combination therapy experienced a significant delay in time to first AIDS-defining event or death compared with those assigned to zidovudine monotherapy.
Schooley
R T
RT
University of Colorado Health Science Center, Denver 80262, USA.
Ramirez-Ronda
C
C
Lange
J M
JM
Cooper
D A
DA
Lavelle
J
J
Lefkowitz
L
L
Moore
M
M
Larder
B A
BA
St Clair
M
M
Mulder
J W
JW
McKinnis
R
R
Pennington
K N
KN
Harrigan
P R
PR
Kinghorn
I
I
Steel
H
H
Rooney
J F
JF
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D006679:HIV Seropositivity / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D016047:Zalcitabine / Q000009:adverse effects / Q000627:therapeutic use*; D015215:Zidovudine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000998:Antiviral Agents; D012367:RNA, Viral; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine