Virologic and CD4 cell response to zidovudine or zidovudine and lamivudinefollowing didanosine treatment of human immunodeficiency virus infection

To optimize nucleoside reverse transcriptase inhibitor (nRTI) antiretrovira l therapy, 137 subjects who had been treated with didanosine monotherapy fo r more than 3 years in the AIDS Clinical Trials Group (ACTG) 175 study were randomized to zidovudine and didanosine (dual therapy) or zidovudine, dida nosine, and lamivudine (triple therapy). Evaluation of early (8 week) chang e in HIV plasma RNA demonstrated that addition of lamivudine and zidovudine provided significantly greater virologic suppression compared to the addit ion of zidovudine alone (mean decrease of 1.27 vs. 0.74 log(10) copies/ml, n = 108, p = 0.007). Both dual and triple therapy provided significant long -term decreases (from study entry to mean at Weeks 40 and 48) in HIV plasma RNA: 0.62 and 0.86 log(10) copies/ml, respectively (n = 110). However, the difference between treatments was not significant (p = 0.16). At 48 weeks, 26% of subjects starting study treatment had <500 copies/ml of plasma HIV RNA. The CD4 count response was greater at 4 weeks for triple versus dual t herapy: a mean increase of 51 vs. 12 CD4 cells/ml(3) (n = 126, p = 0.039). The difference at Weeks 40 and 48 was not significant (a 22 cell increase v s. a 1 cell decrease, n = 129, p = 0.41). Zidovudine and didanosine treatme nt, with or without lamivudine, was well tolerated and only 2 of 137 (1.5%) of study participants developed an AIDS-defining event over 48 weeks.