Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. Wellcome Resistance Study Collaborative Group.

Author(s): Schooley RT, Ramirez-Ronda C, Lange JM, Cooper DA, Lavelle J, Lefkowitz L, Moore M, Larder BA, St Clair M, Mulder JW, McKinnis R, Pennington KN, Harrigan PR, Kinghorn I, Steel H, Rooney JF

Affiliation(s): University of Colorado Health Science Center, Denver 80262, USA.

Publication date & source: 1996-06, J Infect Dis., 173(6):1354-66.

Publication type: Clinical Trial; Multicenter Study; Randomized Controlled Trial

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.