Virologic and CD4(+) cell responses to new nucleoside regimens: switching to stavudine or adding lamivudine after prolonged zidovudine treatment of human immunodeficiency virus infection

Clinical benefit of zidovudine alone in the treatment of HIV infection wane s after several years, with decreasing CD4(+) cell numbers and increasing H IV RNA in plasma. To develop treatment strategies following prolonged zidov udine treatment, 92 subjects from the AIDS Clinical Trials Group (ACTG) 175 study after a median of 3.6 years of zidovudine monotherapy were randomize d to treatment with stavudine or zidovudine and lamivudine. Evaluation of l ong-term changes, the average of 40- and 48-week HIV plasma RNA, demonstrat ed that lamivudine and zidovudine provided significantly greater virologic suppression compared with stavudine (mean decrease 0.70 versus 0.18 log(10) copies/ml, p = 0.003). Twenty-nine percent of zidovudine plus lamivudine r ecipients had HIV RNA levels below 500 copies per milliliter at 48 weeks as compared with 4% of stavudine recipients (p = 0.02). Both regimens signifi cantly increased CD4(+) cell numbers, the means of weeks 40 and 48 rose to 49 and 36 CD4(+) cells per cubic millimeter among zidovudine plus lamivudin e and stavudine recipients, respectively. Treatments were well tolerated an d only 3 of 92 subjects died or developed AIDS within 48 weeks. In zidovudi ne-experienced subjects, addition of lamivudine resulted in significantly d ecreased plasma HIV RNA levels at 48 weeks compared with treatment with sta vudine alone.