Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial

Objective: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddl), or stavudine (d4T). Design: Randomized, placebo-controlled, partially double-blinded multicenter study. Setting: Adult AIDS Clinical Trials Units. Patients: Treatment-naive HIV-infected adults with 200-600 x 10⁶ CD4 T lymphocytes/l. Interventions: Patients were openly randomized to a d4T or a ddl limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddl (400 mg/day), ddl plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos. After 24 weeks 3TC was added for patients assigned to the monotherapy arms. Main outcome measure: The reduction in plasma HIV-1 RNA level at weeks 24 and 48. Results: Two hundred ninety-nine patients were enrolled. After 24 weeks the mean reduction in plasma HIV-1 RNA copies/ml from baseline was 0.49 log₁₀ (d4T monotherapy) versus 1.03 log₁₀ (d4T plus 3TC; P = 0.001), and 0.68 log₁₀ (ddl monotherapy) versus 0.82 log₁₀ (ddl plus 3TC; P > 0.22). After 48 weeks the mean reduction was 1.08 log₁₀ (d4T plus 3TC) versus 1.01 log₁₀ (ZDV plus 3TC) in the d4T limb (P = 0.66), and 0.94 log₁₀ (ddl plus 3TC) versus 0.88 log₁₀ (ZDV plus 3TC; P = 0.70) in the ddl limb. Conclusions: 3TC added significantly to the virologic effects of d4T, but not ddl, in treatment-naive patients 3TC plus d4T produced virologic changes comparable to those of 3TC plus ZDV. These results support the use of 3TC with either ZDV or d4T as a component of initial combination antiretroviral therapy.